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Identification of potential bacterial players in colorectal tumorigenesis has been a focus of intense research. Herein, we find that Clostridium symbiosum (C. symbiosum) is selectively enriched in tumor tissues of patients with colorectal cancer (CRC) and associated with higher colorectal adenoma recurrence after endoscopic polypectomy. The tumorigenic effect of C. symbiosum is observed in multiple murine models. Single-cell transcriptome profiling along with functional assays demonstrates that C. symbiosum promotes the proliferation of colonic stem cells and enhances cancer stemness. Mechanistically, C. symbiosum intensifies cellular cholesterol synthesis by producing branched-chain amino acids (BCAAs), which sequentially activates Sonic hedgehog signaling. Low dietary BCAA intake or blockade of cholesterol synthesis by statins could partially abrogate the C. symbiosum-induced cell proliferation in vivo and in vitro. Collectively, we reveal C. symbiosum as a bacterial driver of colorectal tumorigenesis, thus identifying a potential target in CRC prediction, prevention, and treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Fusobacterium nucleatum can bind to host cells and potentiate intestinal tumorigenesis. Here we used a genome-wide screen to identify an adhesin, RadD, which facilitates the attachment of F. nucleatum to colorectal cancer (CRC) cells in vitro. RadD directly binds to CD147, a receptor overexpressed on CRC cell surfaces, which initiated a PI3K-AKT-NF-κB-MMP9 cascade, subsequently enhancing tumorigenesis in mice. Clinical specimen analysis showed that elevated radD gene levels in CRC tissues correlated positively with activated oncogenic signalling and poor patient outcomes. Finally, blockade of the interaction between RadD and CD147 in mice effectively impaired F. nucleatum attachment and attenuated F. nucleatum-induced oncogenic response. Together, our study provides insights into an oncogenic mechanism driven by F. nucleatum RadD and suggests that the RadD-CD147 interaction could be a potential therapeutic target for CRC., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Sepsis-induced acute kidney injury (S-AKI) is one of the most serious life-threatening complications of sepsis. The pathogenesis of S-AKI is complex and there is no effective specific treatment. Therefore, it is crucial to choose suitable preclinical models that are highly similar to human S-AKI to study the pathogenesis and drug treatment. In this review, we summarized recent advances in the development models of S-AKI, providing reference for the reasonable selection of experimental models as basic research and drug development of S-AKI., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of this study is to investigate the role of high mobility group protein B1 (HMGB1) in placental development and fetal growth., Methods: We employed the Cre-loxP recombination system to establish a placenta-specific HMGB1 knockout mouse model. Breeding HMGB1flox/flox mice with Elf5-Cre mice facilitated the knockout, leveraging Elf5 expression in extra-embryonic ectoderm, ectoplacental cone, and trophoblast giant cells at 12.5 days of embryonic development. The primary goal of this model was to elucidate the molecular mechanism of HMGB1 in placental development, assessing parameters such as placental weight, fetal weight, and bone development. Additionally, we utilized lentiviral interference and overexpression of HMGB1 in human trophoblast cells to further investigate HMGB1's functional role., Results: Our findings indicate that the HMGB1flox/floxElf5cre/+ mouse displays fetal growth restriction, characterized by decreased placental and fetal weight and impaired bone development. The absence of HMGB1 inhibits autophagosome formation, impairs lysosomal degradation, and disrupts autophagic flux. Depletion of HMGB1 in human trophoblast cells also suppresses cell viability, proliferation, migration, and invasion by inhibiting the ERK signaling pathway. Overexpression of HMGB1 observed the opposite phenotypes., Conclusions: HMGB1 participates in the regulation of autophagy through the ERK signaling pathway and affects placental development., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Polymyxin-induced nephrotoxicity (PIN) is a major safety concern and challenge in clinical practice, which limits the clinical use of polymyxins. This study aims to investigate the risk factors and to develop a scoring tool for the early prediction of PIN., Methods: Data on critically ill patients who received intravenous polymyxin B or colistin sulfate for over 24 h were collected. Logistic regression with the least absolute shrinkage and selection operator (LASSO) was used to identify variables that are associated with outcomes. The eXtreme Gradient Boosting (XGB) classifier algorithm was used to further visualize factors with significant differences. A prediction model for PIN was developed through binary logistic regression analysis and the model was assessed by temporal validation and external validation. Finally, a risk-scoring system was developed based on the prediction model., Results: Of 508 patients, 161 (31.6%) patients developed PIN. Polymyxin type, loading dose, septic shock, concomitant vasopressors and baseline blood urea nitrogen (BUN) level were identified as significant predictors of PIN. All validation exhibited great discrimination, with the AUC of 0.742 (95% CI: 0.696-0.787) for internal validation, of 0.708 (95% CI: 0.605-0.810) for temporal validation and of 0.874 (95% CI: 0.759-0.989) for external validation, respectively. A simple risk-scoring tool was developed with a total risk score ranging from -3 to 4, corresponding to a risk of PIN from 0.79% to 81.24%., Conclusions: This study established a prediction model for PIN. Before using polymyxins, the simple risk-scoring tool can effectively identify patients at risk of developing PIN within a range of 7% to 65%., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: This study aimed to investigate the functions of lncRNA H19 on glomerular endothelial structural damage of diabetic nephropathy (DN). Materials and Methods: Rats were fed a high sugar and fat high feed die, and intraperitoneally administrated with streptozotocin (30 mg/kg) to induce DN model. Meanwile, rat glomerular endothelial cells (rGEnCs) were treated with high a level of glucose （HG, 30 mM glucose）to induce structural damage. Results: Our results showed that H19 level was drastically increased in diabetic glomeruli and high-glucose (HG)-stimulated rat glomerular endothelial cells (rGEnCs). Deficiency of H19 ameliorated microalbumin, creatinine, BUN, and histopathological alterations in diabetic rats. In addition, H19 deficiency significantly attenuated the damage of endothelial structure by upregulating the expression of junction proteins ZO-1 and Occludin, glycolcalyx protein Syndecan-1, and endothelial activation marker sVCAM-1 and sICAM-1 in diabetic rats. The in vitro results also showed that H19-siRNA alleviated glycocalyx shedding, tight junctions damage, and endothelial activation in HG-stimulated rGEnCs. Moreover, H19 deficiency significantly enhanced the expression of p-Akt and p-eNOS and NO concentration in vitro and in vivo . Pre-treatment with Akt inhibitor LY294002 abrogated these favourable effects mediated by H19 deficiency. Discussion and Conclusion: These results indicate that H19 deficiency could mitigate the structural damage of glomerular endothelium in DN via activating Akt/eNOS pathway.

Background: Polymyxins have re-emerged as a last-resort therapeutic option for infections caused by carbapenem-resistant gram-negative bacteria. Nephrotoxicity induced by polymyxins is a significant limitation of its use in the clinic. Polymyxin B and colistin sulfate are two widely used active formulations of polymyxins. However, there is a lack of studies conducting a comparative assessment of nephrotoxicity between the two formulations. This study aimed to compare the nephrotoxicity of polymyxin B and colistin sulfate in critically ill patients., Methods: We conducted a retrospective cohort study among critically ill patients who received intravenous polymyxin B or colistin sulfate for over 48 h from January 2017 to January 2024. The primary outcome was the incidence of acute kidney injury (AKI) associated with polymyxins, and the secondary outcome was 30-day all-cause mortality. Additionally, the risk factors of polymyxins-induced AKI and 30-day all-cause mortality were identified by Cox proportional hazard regression analysis., Results: A total of 473 patients were included in this study. The overall incidence of AKI was significantly higher in patients who received polymyxin B compared to those who received colistin sulfate in the unmatched cohort (20.8% vs. 9.0%, p = 0.002) and in the propensity score matching cohort (21.1% vs. 7.0%, p = 0.004), respectively. However, there was no significant difference in 30-day all-cause mortality between the two groups. Polymyxin type, septic shock, and concomitant use of vasopressors were identified as independent risk factors for polymyxin-induced AKI., Conclusions: The prevalence of AKI was higher among patients who received polymyxin B compared to those treated with colistin sulfate. However, there was no significant difference in 30-day all-cause mortality between the two groups. Further prospective, multicenter studies with larger sample sizes are needed to validate these findings., (© 2024 Pharmacotherapy Publications, Inc.)

This study aimed to establish a predictive model for the risk of post-thoracic endovascular aortic repair (TEVAR) post-implantation syndrome (PIS) in type B aortic dissection (TBAD) patients, assisting clinical physicians in early risk stratification and decision management for high-risk PIS patients. This study retrospectively analyzed the clinical data of 547 consecutive TBAD patients who underwent TEVAR treatment at our hospital. Feature variables were selected through LASSO regression and logistic regression analysis to construct a nomogram predictive model, and the model's performance was evaluated. The optimal cutoff value for the PIS risk nomogram score was calculated through receiver operating characteristic (ROC) curve analysis, further dividing patients into high-risk group (HRG) and low-risk group (LRG), and comparing the short to midterm postoperative outcomes between the two groups. In the end, a total of 158 cases (28.9%) experienced PIS. Through LASSO regression analysis and multivariable logistic regression analysis, variables including age, emergency surgery, operative time, contrast medium volume, and number of main prosthesis stents were selected to construct the nomogram predictive model. The model achieved an area under the curve (AUC) of 0.86 in the training set and 0.82 in the test set. Results from calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC) demonstrated that the predictive model exhibited good performance and clinical utility. Furthermore, after comparing the postoperative outcomes of HRG and LRG patients, we found that the incidence of postoperative PIS significantly increased in HRG patients. The duration of ICU stay and mechanical assistance time was prolonged, and the incidence of postoperative type II entry flow and acute kidney injury (AKI) was higher. The risk of aortic-related adverse events (ARAEs) and major adverse events (MAEs) at the first and twelfth months of follow-up also significantly increased. However, there was no significant difference in the mortality rate during hospitalization. This study established a nomogram model for predicting the risk of PIS in patients with TBAD undergoing TEVAR. It serves as a practical tool to assist clinicians in early risk stratification and decision-making management for patients., (© 2024. The Author(s).)

Background: This study aimed to investigate alterations in serum markers [creatine kinase-MB (CKMB), cardiac troponin T (cTnT), myoglobin (Myo), B-type natriuretic peptide (BNP), D-dimer (DD), procalcitonin (PCT) and interleukin-6 (IL6)] in early Omicron variant infection and analyzed their correlation with clinical parameters., Methods: Retrospective analysis of 1,138 mild/asymptomatic cases at Tianjin First Central Hospital, including age, gender, serum markers and nucleic acid test results. Statistical analysis used SPSS software, version 24.0., Results: Elevated cTnT, BNP (125-400), and DD (0.55-1.10) levels were prevalent at 12.92%, 15.64%, and 14.50%, respectively. Females had significantly higher proportions with slightly elevated BNP (19.34%) and DD (19.69%) levels. Patients over 35 had a higher proportion of slight elevation in BNP (20.00%). Abnormal levels of serum markers were significantly associated with older age, increased PCT and IL6 levels, as well as delayed nucleic acid clearance. Additionally, levels of immunoglobulin G (IgG) were notably reduced in these cases. Patients with prolonged nucleic acid clearance (>14 days) had higher BNP and DD levels upon admission. Logistic regression identified PCT (OR = 237.95) as the most significant risk factor for abnormal serum markers for cardiovascular system injury., Conclusion: Early Omicron infection might do subclinical damage to the cardiovascular system. Elevated cTnT, BNP and DD levels were correlated with age, gender, inflammatory factors, and IgG. Notably, high PCT level emerged as the most robust predictor of abnormal serum biomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Cao, Xie, Yi, Liu, Zhang, Yue, Li, Zhou and Mu.)

Objective: To evaluate the effect of preemptive analgesia with ibuprofen on postoperative pain following single posterior tooth implantation, aiming to provide a clinical reference for its application. Methods: A multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted. A total of 82 participants were included in the trial, meeting the eligibility criteria from April 2022 to April 2024 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), Beijing Chao-Yang Hospital, Capital Medical University (20 cases). Participants were randomly assigned in a 1∶1 ratio to either the ibuprofen group or the control group, with each group comprising 41 individuals. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups received the same postoperative analgesic regimen for 3 days. Pain scores were assessed using the Numerical rating scale (NRS) at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h postoperatively, and the additional use of analgesic medication was recorded from days 4 to 6 postoperatively. Results: A total of 82 participants were initially enrolled in the study, with 7 dropouts (4 from the control group and 3 from the ibuprofen group), resulting in 75 participants (37 in the control group and 38 in the ibuprofen group) completing the trial. There were no reports of adverse events such as nausea or vomiting among the participants. The ibuprofen group exhibited significantly lower pain scores at 4 h, 6 h and 8 h [1.0 (0.0, 2.0), 1.0 (0.0, 2.0), 1.5 (0.0, 3.0) ] postoperatively compared to the control group 4 h, 6 h and 8 h [2.0 (1.0, 3.0), 3.0 (1.5, 4.0), 2.0 (1.0, 4.0)] ( Z =-1.99, P =0.047; Z =-3.01, P =0.003; Z =2.10, P =0.036). The proportions of patients requiring additional analgesic medication between days 4 and 6 post-surgery were 18.4% (7/38) in the ibuprofen group and 27.0% (10/37) in the control group, with no significant difference (χ 2 =0.79, P =0.373). The median additional medication usage postoperatively was [0.0 (0.0, 0.0) pills] in the ibuprofen group and [0.0 (0.0, 1.0) pills] in the control group, with no significant difference ( Z =-0.78, P =0.439). Conclusions: Preemptive analgesia with ibuprofen effectively reduces postoperative pain following tooth implantation, representing a safe and effective perioperative pain management strategy.

Competing Interests: Competing interests: None declared.

The etiology of preeclampsia (PE), a complex and multifactorial condition, remains incompletely understood. DNA methylation, which is primarily regulated by three DNA methyltransferases (DNMTs), DNMT1, DNMT3A, and DNMT3B, plays a vital role in early embryonic development and trophectoderm differentiation. Yet, how DNMTs modulate trophoblast fusion and PE development remains unclear. In this study, we found that the DNMTs expression was downregulated during trophoblast cells fusion. Downregulation of DNMTs was observed during the reconstruction of the denuded syncytiotrophoblast (STB) layer of placental explants. Additionally, overexpression of DNMTs inhibited trophoblast fusion. Conversely, treatment with the DNA methylation inhibitor 5-aza-CdR decreased the expression of DNMTs and promoted trophoblast fusion. A combined analysis of DNA methylation data and gene transcriptome data obtained from the primary cytotrophoblasts (CTBs) fusion process identified 104 potential methylation-regulated differentially expressed genes (MeDEGs) with upregulated expression due to DNA demethylation, including CD59, TNFAIP3, SDC1, and CDK6. The transcription regulation region (TRR) of TNFAIP3 showed a hypomethylation with induction of 5-aza-CdR, which facilitated CREB recruitment and thereby participated in regulating trophoblast fusion. More importantly, clinical correlation analysis of PE showed that the abnormal increase in DNMTs may be involved in the development of PE. This study identified placental DNA methylation-regulated genes that may contribute to PE, offering a novel perspective on the role of epigenetics in trophoblast fusion and its implication in PE development., (© 2024 Federation of American Societies for Experimental Biology.)

Objective: To understand the prevalence of major chronic diseases of diabetes, cardiovascular disease and malignant tumor in people living with HIV in Taizhou. Methods: The data were collected from China Information System for Disease Control and Prevention and Taizhou Chronic Disease Information Management System. A total of 5 126 people living HIV under follow-up in Taizhou from 1998 to 2022 were included in the analysis. Software SAS 9.4 was used for χ 2 test, trend analysis and logistic regression analysis. Results: In the 5 126 people living with HIV, the reported prevalence rates of diabetes,cardiovascular disease and malignant tumor were 10.28% (527/5 126),3.98% (204/5 126) and 6.01% (308/5 126), respectively. 37.00% (195/527) and 48.58% (256/527), 40.20% (82/204) and 48.53% (99/204), 37.66% (116/308) and 48.38% (149/308) were diagnosed as diabetes, cardiovascular disease and malignant tumor before and after confirmation of HIV infection. From 2013 to 2022, the proportion of HIV infected people diagnosed with diabetes, cardiovascular disease and malignant tumor after confirmation increased (trend χ 2 =79.98, P <0.001; trend χ 2 =17.44, P <0.001; trend χ 2 =32.06, P <0.001). Based on the analysis on the factors for complicated chronic diseases in people living with HIV, it was found that women under 60 years old (a OR =0.66, 95% CI : 0.50-0.86) and those with access to antiviral treatment for >5 years before 2016 (a OR =0.54,95% CI :0.37-0.78) were less likely to develop complicated chronic diseases, and those under 60 years old with initial CD4 + T lymphocytes counts <200 cells/µl (a OR =1.32, 95% CI : 1.02-1.70), those aged 40-49 and 50-59 years (a OR =2.88, 95% CI :2.20-3.79; a OR =5.43, 95% CI : 4.10-7.21) as well as those without a record of treatment medication use after 2016 (a OR =1.95,95% CI :1.20-3.16) were more likely to develop complicated chronic diseases. The probability of developing complicated chronic diseases might increase with age in people living with HIV. Conclusions: From 1998 to 2022, there was a certain proportion of complicated chronic diseases among HIV infected individuals in Taizhou, and the proportion of diagnosed cases increased after HIV infection was confirmed. It is necessary to conduct early chronic disease screening, behavior intervention and standardized management in people living with HIV.

Objective: This study aims to develop a predictive model for the risk of major adverse events (MAEs) in type A aortic dissection (AAAD) patients with malnutrition after surgery, utilizing machine learning (ML) algorithms., Methods: We retrospectively collected clinical data from AAAD patients with malnutrition who underwent surgical treatment at our center. Through least absolute shrinkage and selection operator (LASSO) regression analysis, we screened for preoperative and intraoperative characteristic variables. Based on the random forest (RF) algorithm, we constructed a ML predictive model, and further evaluated and interpreted this model., Results: Through LASSO regression analysis and univariate analysis, we ultimately selected seven feature variables for modeling. After comparing six different ML models, we confirmed that the RF model demonstrated the best predictive performance in this dataset. Subsequently, we constructed a model using the RF algorithm to predict the risk of postoperative MAEs in AAAD patients with malnutrition. The test set results indicated that this model has excellent predictive efficacy and clinical applicability. Finally, we employed the Shapley additive explanations (SHAP) method to further interpret the predictions of this model., Conclusion: We have successfully constructed a risk prediction model for postoperative MAEs in AAAD patients with malnutrition using the RF algorithm, and we have interpreted the model through the SHAP method. This model aids clinicians in early identification of high-risk patients for MAEs, thereby potentially mitigating adverse clinical outcomes associated with malnutrition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xie, Lin, Xie, Wu, Qiu, Lan and Chen.)

The eyes are one of the most important sensory organs in the human body. Currently, diseases such as limbal stem cell deficiency, cataract, retinitis pigmentosa and dry eye seriously threaten the quality of people's lives, and the treatment of advanced blinding eye disease and dry eye is ineffective and costly. Thus, new treatment modalities are urgently needed to improve patients' symptoms and suffering. In recent years, stem cell-derived three-dimensional structural organoids have been shown to mimic specific structures and functions similar to those of organs in the human body. Currently, 3D culture systems are used to construct organoids for different ocular growth and development models and ocular disease models to explore their physiological and pathological mechanisms. Eye organoids can also be used as a platform for drug screening. This paper reviews the latest research progress in regard to eye organoids (the cornea, lens, retina, lacrimal gland, and conjunctiva)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The regulatory mechanism of the transcription factor GATA3 in the differentiation and maturation process of extravillous trophoblasts (EVT) in early pregnancy placenta, as well as its relevance to the occurrence of pregnancy disorders, remains poorly understood. This study leveraged single-cell RNA sequencing data from placental organoid models and placental tissue to explore the dynamic changes in GATA3 expression during EVT maturation. The expression pattern exhibited an initial upregulation followed by subsequent downregulation, with aberrant GATA3 localization observed in cases of recurrent miscarriage (RM). By identifying global targets regulated by GATA3 in primary placental EVT cells, JEG3, and HTR8/SVneo cell lines, this study offered insights into its regulatory mechanisms across different EVT cell models. Shared regulatory targets among these cell types and activation of trophoblast cell marker genes emphasized the importance of GATA3 in EVT differentiation and maturation. Knockdown of GATA3 in JEG3 cells led to repression of GATA3-induced epithelial-mesenchymal transition (EMT), as evidenced by changes in marker gene expression levels and enhanced migration ability. Additionally, interference with GATA3 accelerated cellular senescence, as indicated by reduced proliferation rates and increased activity levels for senescence-associated β-galactosidase enzyme, along with elevated expression levels for senescence-associated genes. This study provides comprehensive insights into the dual role of GATA3 in regulating EMT and cellular senescence during EVT differentiation, shedding light on the dynamic changes in GATA3 expression in normal and pathological placental conditions., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Xpert MTB/RIF Ultra (Ultra) is an automated molecular test for the detection of Mycobacterium tuberculosis in sputum. We compared the sensitivity of Ultra to that of mycobacterial growth indicator tube (MGIT) liquid culture, considered the most sensitive assay in routine clinical use., Methods: In this prospective, multicentre, cross-sectional diagnostic accuracy study, we used a non-inferiority design to assess whether the sensitivity of a single Ultra test was non-inferior to that of a single liquid culture for detection of M tuberculosis in sputum. We enrolled adults (age ≥18 years) with pulmonary tuberculosis symptoms in 11 countries and each adult provided three sputum specimens with a minimum volume of 2 mL over 2 days. Ultra was done directly on sputum 1, and Ultra and MGIT liquid culture were done on resuspended pellet from sputum 2. Results of MGIT and solid media cultures done on sputum 3 were considered the reference standard. The pre-defined non-inferiority margin was 5·0%., Findings: Between Feb 18, 2016, and Dec 4, 2019, we enrolled 2906 participants. 2600 (89%) participants were analysed, including 639 (25%) of 2600 who were positive for tuberculosis by the reference standard. Of the 2357 included in the non-inferiority analysis, 877 (37%) were HIV-positive and 984 (42%) were female. Sensitivity of Ultra performed directly on sputum 1 was non-inferior to that of sputum 2 MGIT culture (MGIT 91·1% vs Ultra 91·9%; difference -0·8 percentage points; 95% CI -2·8 to 1·1). Sensitivity of Ultra performed on sputum 2 pellet was also non-inferior to that of sputum 2 MGIT (MGIT 91·1% vs Ultra 91·9%; difference -0·8 percentage points; -2·7 to 1·0)., Interpretation: For the detection of M tuberculosis in sputum from adults with respiratory symptoms, there was no difference in sensitivity of a single Ultra test to that of a single MGIT culture. Highly sensitive, rapid molecular approaches for M tuberculosis detection, combined with advances in genotypic methods for drug resistance detection, have potential to replace culture., Funding: US National Institute of Allergy and Infectious Diseases., Competing Interests: Declaration of interests SGS was employed by FIND during conduct of the study. FIND is a not-for-profit foundation that supports the evaluation of publicly prioritised tuberculosis assays and the implementation of WHO-approved (guidance and prequalification) assays using donor grants. FIND has product evaluation agreements with several private sector companies that design diagnostics and related products for treatment of tuberculosis and other diseases. These agreements strictly define FIND’s independence and neutrality with regard to the companies whose products get evaluated and describe roles and responsibilities. DA receives income from licence payments from Cepheid to Rutgers University and reports receiving research contracts and research support from Cepheid. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The surgical treatment of recurrent nasopharyngeal carcinoma (rNPC) involving the internal carotid artery (ICA) is challenging, as the massive bleeding caused by intraoperative rupture of the ICA is life-threatening. We reported that ICA embolization is an effective pretreatment to avoid fatal bleeding, but some patients cannot tolerate the procedure. We used endovascular vascular protection (ICA stents), vascular sacrifice (bypass grafting) and extravascular vascular protection (transcervical external stent placement) of the ICA to provide alternative options for these patients. METHODOLOGYy: This study enrolled patients with rNPC adjacent to or invading the ICA who were unsuitable for ICA embolization from January 2015 to June 2020. ICA pretreatment combined with endoscopic nasopharyngectomy (ENPG) was performed for the 30 patients. We report the survival outcome and incidence of complications after ICA pretreatment., Results: ICA pretreatment was performed for the 30 enrolled patients, among whom 8 underwent endoscopic-assisted transcervical protection of the parapharyngeal ICA combined with ENPG, 6 underwent bypass grafting, and 16 underwent ICA stent implantation followed by ENPG. After pretreatment, at a median follow-up of 43 months (range, 2-80 months), the 3-year locoregional overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 62.9%, 61.3%, 70.2%, and 71.4%, respectively., Conclusions: ICA pretreatment combined with salvage ENPG enables the feasible and effective resection of rNPC lesions involving the ICA in patients who cannot tolerate ICA embolization. Therefore, this treatment may be an effective method for improving outcomes. Multidisciplinary therapy is needed to reduce operation-related complications.

Objective: Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with special biological features. Controversies exist regarding the treatment approach and prognostic factors in the IMRT era. This study aimed to evaluate the long-term outcomes and management approaches in NACC., Methods: Fifty patients with NACC at our institution between 2010 and 2020 were reviewed. Sixteen patients received primary radiotherapy (RT), and 34 patients underwent primary surgery., Results: Between January 2010 and October 2020, a total of 50 patients with pathologically proven NACC were included in our analysis. The median follow-up time was 58.5 months (range: 6.0-151.0 months). The 5-year overall survival rate (OS) and progression-free survival rate (PFS) were 83.9% and 67.5%, respectively. The 5-year OS rates of patients whose primary treatment was surgery and RT were 90.0% and 67.3%, respectively (log-rank P = 0.028). The 5-year PFS rates of patients whose primary treatment was surgery or RT were 80.8% and 40.7%, respectively (log-rank P = 0.024). Multivariate analyses showed that nerve invasion and the pattern of primary treatment were independent factors associated with PFS., Conclusions: Due to the relative insensitivity to radiation, primary surgery seemed to provide a better chance of disease control and improved survival in NACC. Meanwhile, postoperative radiotherapy should be performed for advanced stage or residual tumours. Cranial nerve invasion and treatment pattern might be important factors affecting the prognosis of patients with NACC., (© 2024. The Author(s).)

Study Question: Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)?, Summary Answer: PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression., What Is Known Already: High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood., Study Design, Size, Duration: Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated., Participants/materials, Setting, Methods: The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches., Main Results and the Role of Chance: Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice., Large Scale Data: N/A., Limitations, Reasons for Caution: Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls., Wider Implications of the Findings: Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus., Study Funding/competing Interest(s): This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest., Trial Registration Number: N/A., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

ConspectusRecent years have witnessed the development of cluster materials as they are atomically precise molecules with uniform size and solution-processability, which are unattainable with traditional nanoparticles or framework materials. The motivation for studying Al(III) chemistry is not only to understand the aggregation process of aluminum in the environment but also to develop novel low-cost materials given its natural abundance. However, the Al-related clusters are underdeveloped compared to the coinage metals, lanthanides, and transition metals. The challenge in isolating crystalline compounds is the lack of an effective method to realize the controllable hydrolysis of Al(III) ions. Compared with the traditional hydrolysis of inorganic Al(III) salts in highly alkaline solutions and hydrolysis of aluminum trialkyl compounds conducted carefully in an inert operating environment, we herein developed an effective way to control the hydrolysis of aluminum isopropanol through an alcoxalation reaction. By solvothermal/low melting point solid melting synthesis and using "ligand aggregation, solvent regulation, and supracluster assembly" strategies, our laboratory has established an organic-inorganic hybrid system of aluminum oxo clusters (AlOCs). The employment of organic ligands promotes the aggregation and slows the hydrolysis of Al(III) ions, which in turn improves the crystallization process. The regulation of the structure types can be achieved through the selection of ligands and the supporting solvents. Compared with the traditional condensed polyoxoaluminates, we successfully isolated a broad range of porous AlOCs, including aluminum molecular rings and Archimedes aluminum oxo cages. By studying ring expansion, structural transformation, and intermolecular supramolecular assembly, we demonstrate unique and unprecedented structural controllability and assembly behavior in cluster science. The advancement of this universal synthetic method is to realize materials customization through modularly oriented supracluster assembly. In this Account, we will provide a clear-cut definition and terminology of "ligand aggregation, solvent regulation, and supracluster assembly". Then we will discuss the discovery in this area by using a strategy, such as aluminum molecular ring, ring size expansion, ring supracluster assembly, etc. Furthermore, given the internal and external pore structures, as well as the solubility and modifiability of the AlOCs, we will demonstrate their potential applications in both the solid and liquid phases, such as iodine capture, the optical limiting responses, and dopant in polymer dielectrics. The strategy herein can be applied to extensive cluster science and promote the research of main group element chemistry. The new synthetic method, fascinating clusters, and unprecedented assembly behaviors we have discovered will advance Al(III) chemistry and will also lay the foundation for functional applications.

Purpose: To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis., Methods: A total of 282 healthy young male volunteers aged 18 - 20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conformed to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q 1 , Q 3 ) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy., Results: Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4% (66 cases). These patients showed higher percentages of lean body mass (p = 0.001), total body water (TBW, p = 0.006), extracellular water (p = 0.020) and intracellular water (p = 0.010) as well as a larger ratio of basal metabolic rate/total weight (p = 0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat (p = 0.001) and body fat mass index (p = 0.002) were lower. Logistic regression analysis showed that TBW percentage > 65.35% (p = 0.050, odds ratio = 3.114) and 3rd space water > 0.95% (p = 0.045, odds ratio = 2.342) were independent risk factors for lower extremity muscle injuries., Conclusion: TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training., (Copyright © 2024 Chinese Medical Association. Production and hosting by Elsevier B.V. All rights reserved.)

Introduction: The aim of this study is to develop a model for predicting the risk of prolonged mechanical ventilation (PMV) following surgical repair of acute type A aortic dissection (AAAD)., Methods: We retrospectively collected clinical data from 381 patients with AAAD who underwent emergency surgery. Clinical features variables for predicting postoperative PMV were selected through univariate analysis, least absolute shrinkage and selection operator regression analysis, and multivariate logistic regression analysis. A risk prediction model was established using a nomogram. The model's accuracy and reliability were evaluated using the area under the curve of the receiver operating characteristic curve and the calibration curve. Internal validation of the model was performed using bootstrap resampling. The clinical applicability of the model was assessed using decision curve analysis and clinical impact curve., Results: Among the 381 patients, 199 patients (52.2%) experienced postoperative PMV. The predictive model exhibited good discriminative ability (area under the curve = 0.827, 95% confidence interval: 0.786-0.868, P < 0.05). The calibration curve confirmed that the predicted outcomes of the model closely approximated the ideal curve, indicating agreement between the predicted and actual results (with an average absolute error of 0.01 based on 1000 bootstrap resampling). The decision curve analysis curve demonstrated that the model has significant clinical value., Conclusions: The nomogram model established in this study can be used to predict the risk of postoperative PMV in patients with AAAD. It serves as a practical tool to assist clinicians in adjusting treatment strategies promptly and implementing targeted therapeutic measures., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The transformation and implementation of clinical practice guidelines for integrated traditional Chinese medicine (TCM) and Western medicine (WM) is crucial to the adoption of medical science and technological findings and is an important way for TCM to be made available to the world. First, clinical practice guidelines (CPGs) of TCM and WM integration in recent years was analyzed to clarify the current situation and problems in the existing guidelines according to the following four perspectives: (1) perspective of TCM and WM integration in guidelines, (2) diagnosis Using integrated TCM and WM, (3) integration of TCM and WM treatment, (4) promoting TCM and WM integration. Secondly, the information and quality evaluation of CPGs for integrated Chinese and Western medicine in 2020-2022 were analyzed to explore the degree and methods of integration of Chinese and Western medicine guidelines. And last this study aimed to lay a foundation for the further establishment of Chinese characteristic, repeatable, and calculable clinical practice guidelines of TCM and WM integration., (© 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study was aimed to investigate the risk factors of necrotizing enterocolitis (NEC) in twin preterm infants., Methods: The clinical data of 67 pairs of twin preterm infants admitted to the neonatal department of our hospital from January 2010 to December 2021 were retrospectively collected. One of the twins had NEC (Bell II and above) and the other twin without NEC. They were divided into NEC group and control group according to whether NEC occurred or not., Results: Univariate analysis showed that NEC was associated with congenital heart disease, small for gestational age, mild asphyxia at birth and feeding intolerance (P < 0.05)., Conclusion: Occurrence of NEC was associated with congenital heart disease, small for gestational age, and asphyxia at birth. For twin preterm infants with congenital heart disease, small for gestational age, or asphyxia at birth, special attention should be paid to the occurrence of NEC to minimize and avoid the occurrence of NEC., (© 2024. The Author(s).)

Objective: To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application. Methods: This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively. Results: All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs . 4.0 (3.0, 5.0)] ( Z =-3.73, P <0.001), 6 h [2.0 (1.0, 4.0) vs . 5.0(2.5, 6.0)] ( Z =-3.38, P <0.001), and 8 h [2.0 (1.0, 4.0) vs . 5.0 (2.0, 6.0)] ( Z =-2.11, P =0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively ( P >0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs . 1.0 (0.0, 3.0)] ( Z =-2.81, P =0.005). Conclusions: A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.

Acute type A aortic dissection (AAAD) has a high probability of postoperative adverse outcomes (PAO) after emergency surgery, so exploring the risk factors for PAO during hospitalization is key to reducing postoperative mortality and improving prognosis. An artificial intelligence approach was used to build a predictive model of PAO by clinical data-driven machine learning to predict the incidence of PAO after total arch repair for AAAD. This study included 380 patients with AAAD. The clinical features that are associated with PAO were selected using the LASSO regression analysis. Six different machine learning algorithms were tried for modeling, and the performance of each model was analyzed comprehensively using receiver operating characteristic curves, calibration curve, precision recall curve, and decision analysis curves. Explain the optimal model through Shapley Additive Explanation (SHAP) and perform an individualized risk assessment. After comprehensive analysis, the authors believe that the extreme gradient boosting (XGBoost) model is the optimal model, with better performance than other models. The authors successfully built a prediction model for PAO in AAAD patients based on the XGBoost algorithm and interpreted the model with the SHAP method, which helps to identify high-risk AAAD patients at an early stage and to adjust individual patient-related clinical treatment plans in a timely manner., (© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: There is a paucity of Chinese studies evaluating the quality of life (QoL) in young acute type A aortic dissection (AAAD) patients with Marfan syndrome., Methods: Young adult AAAD patients (younger than 45 years old) underwent surgical treatment at our institution from January 2017 to December 2020 were consecutive enrolled. The hospital survivors completed 1 year of follow up. Patients were divided into two groups according to the presence or absence of Marfan syndrome (MFS). A 1:1 propensity score matching (PSM) with a caliper 0.2 was conducted to balance potential bias in baseline. The follow-up data were analyzed primarily for change in quality of life and anxiety status., Results: After PSM, 32 comparable pairs were matched. The baseline data were comparable and postoperative complications were similar between groups. In terms of SF-36 scale, the role physical, bodily pain, role emotional and mental health subscales were no significantly improved in MFS patients over time. At 1 year after discharged, the subscale of mental health and bodily pain were significantly lower in the MFS group than in the non-MFS group. In terms of HADS assessments, the level of anxiety in MFS patients was significantly higher than in non-MFS patients at 1 year after discharged., Conclusions: The QoL in young AAAD patients with MFS is lower than those without MFS after surgery. This may be associated with the uncontrollable persistent chronic pain and the uncertainty and concerns for the disease's progression., (© 2024. The Author(s).)

Pulmonary arterial hypertension (PAH) is a complex and fatal cardio-pulmonary vascular disease. Decompensated right ventricular hypertrophy (RVH) caused by cardiomyocyte hypertrophy often leads to fatal heart failure, the leading cause of mortality among patients. Sodium butyrate (SB), a compound known to reduce cardiac hypertrophy, was examined for its potential effect and the underlying mechanism of SB on PAH-RVH. The in vivo study showed that SB alleviated RVH and cardiac dysfunction, as well as improved life span and survival rate in MCT-PAH rats. The in vivo and in vitro experiments showed that SB could attenuate cardiomyocyte hypertrophy by reversing the expressions of H19, let-7g-5p, insulin-like growth factor 1 receptor (IGF1 receptor), and pERK. H19 inhibition restored the level of let-7g-5p and prevented the overexpression of IGF1 receptor and pERK in hypertrophic cardiomyocytes. In addition, dual luciferase assay revealed that H19 demonstrated significant binding with let-7g-5p, acting as its endogenous RNA. Briefly, SB attenuated PAH-RVH by inhibiting the H19 overexpression, restoring the level of let-7g-5p, and hindering IGF1 receptor/ERK activation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Isoniazid (INH) is an important drug in many TB regimens, and unfavorable treatment outcomes can be caused by suboptimal pharmacokinetics. Dose adjustment can be personalized by measuring peak serum concentrations; however, the process involves cold-chain preservation and laboratory techniques such as liquid chromatography (LC)/mass spectrometry (MS), which are unavailable in many high-burden settings. Urine spectrophotometry could provide a low-cost alternative with simple sampling and quantification methods., Methods: We enrolled 56 adult patients on treatment for active TB. Serum was collected at 0, 1, 2, 4, 6, and 8 h for measurement of INH concentrations using validated LC-MS/MS methods. Urine was collected at 0-4, 4-8, and 8-24 h intervals, with INH concentrations measured using colorimetric methods., Results: The median peak serum concentration and total serum exposure over 24 h were 4.8 mg/L and 16.4 mg*hour/L, respectively. Area under the receiver operator characteristic curves for urine values predicting a subtherapeutic serum concentration (peak <3.0 mg/L) were as follows: 0-4 h interval (AUC 0.85, 95% CI 0.7-0.96), 0-8 h interval (AUC 0.85, 95% CI 0.71-0.96), and 0-24 h urine collection interval (AUC 0.84, 95% CI 0.68-0.96)., Conclusion: Urine spectrophotometry may improve feasibility of personalized dosing in high TB burden regions but requires further study of target attainment following dose adjustment based on a urine threshold.

Objective: Endoscopic nasopharyngectomy (ENPG) with en bloc resection has been well accepted in resectable localized recurrent nasopharyngeal carcinoma (rNPC), but it is a difficult technique to master for most otorhinolaryngology head and neck surgeons. Ablation surgery is a new and simplified method to remove tumors. We designed a novel method using low-temperature plasma radiofrequency ablation (LPRA) and evaluated the survival benefit., Methods: A total of 56 localized rNPC patients were explained in detail and retrospectively analyzed. The surgery method was ablated from the resection margin to the center of the tumor. The postmetastatic overall survival (OS), local relapse-free survival (LRFS) rate, progression-free survival (PFS) and distant metastasis-free survival (DMFS) were analyzed using the Kaplan-Meier method and compared by the log-rank test., Results: All surgeries were successfully performed without any severe postoperative complications or deaths. The median operation time of ablation and harvested NSFF respectively were 29 min (range, 15-100 min) and 101 min (range, 30-180 min). The average number of hospital days postoperation was 3 days (range, 2-5 days). All cases (100.0%) had radical ablation with negative resection margins. The nasopharyngeal defects were completely re-epithelialized in 54 (96.4%) patients. As of the data cutoff (September 3, 2023), the median follow-up time was 44.3 months (range, 17.1-52.7 months, 95% CI: 40.4-48.2). The 3-year OS, LRFS, PFS and DMFS of the entire cohort were 92.9% (95% CI: 0.862-0.996), 89.3% (95% CI: 0.813-0.973), 87.5% (95% CI: 0.789-0.961), and 92.9% (95% CI: 0.862-0.996), respectively. Cycles of radiotherapy were independent risk factors for OS (p = 0.003; HR, 32.041; 95% CI: 3.365-305.064), LRFS (p = 0.002; HR, 10.762; 95% CI: 2.440-47.459), PFS (p = 0.004; HR, 7.457; 95% CI: 1.925-28.877), and DMFS (p = 0.002; HR, 34.776; 95% CI: 3.806-317.799)., Conclusion: Radical endoscopic nasopharyngectomy by using low-temperature plasma radiofrequency ablation is a novel, safe and simplified method to master and disseminate for treating resectable rNPC. However, further data and longer follow-up time are needed to prove its efficacy., (© 2023 Wiley Periodicals LLC.)

Macrophages are heterogenic phagocytic cells that play distinct roles in physiological and pathological processes. Targeting different types of macrophages has shown potent therapeutic effects in many diseases. Although many approaches are developed to target anti-inflammatory macrophages, there are few researches on targeting pro-inflammatory macrophages, which is partially attributed to their non-s pecificity phagocytosis of extracellular substances. In this study, a novel recombinant protein is constructed that can be anchored on an exosome membrane with the purpose of targeting pro-inflammatory macrophages via antigen recognition, which is named AnCar-Exo LaIMTS . The data indicate that the phagocytosis efficiencies of pro-inflammatory macrophages for different AnCar-Exo LaIMTS show obvious differences. The AnCar-Exo LaIMTS3 has the best targeting ability for pro-inflammatory macrophages in vitro and in vivo. Mechanically, AnCar-Exo LaIMTS3 can specifically recognize the leucine-rich repeat domain of the TLR4 receptor, and then enter into pro-inflammatory macrophages via the TLR4-mediated receptor endocytosis pathway. Moreover, AnCar-Exo LaIMTS3 can efficiently deliver therapeutic cargo to pro-inflammatory macrophages and inhibit the synovial inflammatory response via downregulation of HIF-1α level, thus ameliorating the severity of arthritis in vivo. Collectively, the work established a novel gene/drug delivery system that can specifically target pro-inflammatory macrophages, which may be beneficial for the treatments of arthritis and other inflammatory diseases., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Due to rising land development, mitigating the negative effects of land use change is becoming a problem. Understanding how land development affects flood inundation is critical for long-term water resource management. This study evaluates the land use change in the Konkoure River Basin and its impact on flood inundation. The land use changes were assessed using Landsat image (level 1) in August 2006 and August 2021. In addition, we used GIS and remote sensing applications to assess the degree of changes that took place in the Konkoure watershed. According to the findings, 32.16% of the total area became built-up areas, and 35.51% was converted to other land uses in Konkoure watershed. Konkoure's most significant change is that 29.50% of forest area transformed into built-up areas and other land uses. The rainfall-runoff-inundation model (RRI) based inundation of the Konkoure River Basin was compared to the MODIS extent between 31 August 2006 and 30 August 2021 flood events. Flood inundation variations in the Konkoure watershed were studied in terms of inundation area, peak inundation depth, runoff volume, and the infiltration rate. As a result, the flood inundation area increased from 139.98 to 198.72 km 2 and the infiltration rate decrease from 7 to 5 mm/h. Moreover, we used flow duration curves (FDCs) to fully comprehend the streamflow processes. The result indicates that the Konkoure watershed has experienced flooding partly due to land use change., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: To compare the prevalence of frailty and related factors in middle-aged and elderly people aged ≥45 years in island and mountainous areas of Taizhou, Zhejiang Province. Methods: Based on cross-sectional design, stratified cluster sampling and quota sampling methods were adopted. One administrative district was randomly selected from each of six coastal and three inland administrative districts in Taizhou during July to August, representing two different geographical terrains. In the island area (Jiaojiang District), all residents aged ≥45 years were included by cluster sampling. In the mountainous area (Xianju County), participants were selected through quota sampling, with same gender and age distributions. Data about their demographic characteristics, lifestyle and health-related factors were collected through questionnaire surveys and laboratory examinations. The prevalence of frailty was assessed using the Fried frailty phenotype scale. Hierarchical analysis and multivariate logistic regression analysis were used to compare the influencing factors of frailty. Results: A total of 1 011 local residents were studied, in whom island and mountainous residents accounted for 48.1% (486/1 011) and 51.9% (525/1 011) respectively; men and women accounted for 45.9% (464/1 011) and 54.1% (547/1 011) respectively. Middle-aged (45-49 years), younger elderly (60-74 years), and older elderly (≥75 years) residents accounted for 38.6% (390/1 011), 44.6% (451/1 011), and 16.8% (170/1 011) respectively. The overall prevalence rate of frailty was 3.6% (36/1 011), the prevalence rate was 3.7% (17/464) in men and 3.5% (19/547) in women. The prevalence rates in age groups 45-59,60-74 years and ≥75 years were 0.3% (1/390), 2.2% (10/451), and 14.7% (25/170), respectively. The prevalence rates of frailty and pre-frailty in island area were 6.0% (29/486) and 39.1% (190/486), respectively, which was higher than those in mountainous area (1.3%, 7/525) and (30.9%, 162/525). After adjusting for potential confounding factors, the risk for frailty in island residents was significantly higher than that in mountainous residents (a OR =1.55,95% CI : 1.07-2.25, P =0.019). In island area, older age (60-74 years:a OR =2.52,95% CI : 1.56-4.13; ≥75 years:a OR =11.65,95% CI :5.38-26.70), being women (a OR =1.94,95% CI : 1.20-3.17), suffering from depression (a OR =1.09,95% CI :1.02-1.17) were associated with frailty symptoms. In mountainous area, older age was also associated with an increased risk of frailty symptoms, but the OR value was lower than those in island area (60-74 years: a OR =1.74,95% CI :1.04-2.94;≥75 years: a OR =4.78,95% CI :2.45-9.50). Polydrug use (a OR =2.08,95% CI : 1.14-3.80) and suffering from depression (a OR =1.10,95% CI : 1.02-1.18) had significant positive association with frailty symptoms. Higher education level had significant negative association with frailty symptoms (junior high school: a OR =0.40,95% CI : 0.21-0.75; senior high school and technical secondary school: a OR =0.29,95% CI : 0.15-0.53; college or above:a OR =0.22,95% CI : 0.11-0.42). Conclusions: The prevalence of frailty in middle-aged and elderly community residents was significantly higher in island area than in mountainous area in Taizhou. The frailty-related factors varied with area. The elderly people (≥75 years) and women in island area had higher risk for frailty. Older age and suffering from depression were the independent risk factors for frailty. It is necessary to pay attention to the health risk factors and special environment in island area, and take comprehensive intervention measures to delay the process of debilitation and improve the quality of life of middle-aged and elderly people.

Ethnopharmacological Relevance: The Antiviral Granules (AG) are derived from the classical famous prescription, which is composed of 9 traditional Chinese medicines, namely Radix Isatidis (called Banlangen, BLG in Chinese), Forsythiae Fructus (called Lianqiao, LQ in Chinese), Gypsum fibrosum, Anemarrhenae Rhizoma (called Zhimu, ZM in Chinese), Phragmitis Rhizoma (called Lugen, LG in Chinese), Rehmanniae Radix (called Dihuang, DH in Chinese), Pogostemonis Herba (called Guanghuoxiang, GHX in Chinese), Acori Tatarinowii Rhizoma (called Shichangpu, SCP in Chinese), and Curcumae Radix (called Yujin, YJ in Chinese), and has shown an excellent therapeutic effect in clinical treatment of influenza. However, there are few studies on the anti-influenza mechanism of AG, and the mechanism of action is still unclear., Aim of the Study: The purpose is to provide the latest information about the clinical efficacy, pharmacodynamic composition and mechanism of AG based on scientific literature, so as to enhance the utilization of AG in the treatment of influenza and related diseases, and promote the development and innovation of novel anti-influenza drugs targeting the influenza virus., Materials and Methods: Enter the data retrieval room, search for Antiviral Granules, as well as the scientific names, common names, and Chinese names of each Chinese medicine. Additionally, search for the relevant clinical applications, pharmacodynamic composition, pharmacological action, and molecular mechanism of both Antiviral Granules and single-ingredient medicines. Keywords includes terms such as "antiviral granules", "influenza", "Isatis indigotica Fort.", "Radix Isatidis", "Banlangeng", "pharmacology", "clinical application", "pharmacologic action", etc. and their combinations. Obtain results from the Web of Science, PubMed, Google Scholar, Sci Finder Scholar, CNKI and other resources., Results: AG is effective in the treatment of influenza and is often used in combination with other drugs to treat viral diseases. Its chemical composition is complex, including alkaloids, polysaccharides, volatile oils, steroid saponins, phenylpropanoids, terpenoids and other compounds. These compounds have a variety of pharmacological activities, which can interfere with the replication cycle of the influenza virus, regulate RIG-I-MAVS, JAK/STAT, TLRs/MyD88, NF-κB signaling pathways and related cytokines, regulate intestinal microorganisms, and protect both the lungs and extrapulmonary organs., Conclusions: AG can overcome the limitations of traditional antiviral drug therapy, play a synergistic role in fighting influenza virus with the characteristics of multi-component, multi-pathway and multi-target therapy, and reverse the bodily function damage caused by influenza virus. AG may be a potential drug in the prevention and treatment of influenza and related diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Tuberculosis (TB) remains one of the leading global causes of mortality. Several methods have been established to detect anti-TB agents in human plasma and serum. However, there is a notable absence of studies analyzing TB drugs in urine. Thus, our objective was to validate a method for quantifying first-line anti-TB agents: isoniazid (INH), pyrazinamide (PZA), ethambutol (ETH), and rifampicin (RIF), along with its metabolite 25-desacetylrifampicin, and degradation products: rifampicin quinone and 3-formyl-rifampicin in 10 µL of urine. Chromatographic separation was achieved using a Kinetex Polar C18 analytical column with gradient elution (5 mM ammonium acetate and acetonitrile with 0.1% formic acid). Mass spectrometry detection was carried out using a triple-quadrupole tandem mass spectrometer operating in positive ion mode. The lower limit of quantification (LLOQ) was 0.5 µg/mL for INH, PZA, ETH, and RIF, and 0.1 µg/mL for RIF's metabolites and degradation products. The method was validated following FDA guidance criteria and successfully applied to the analysis of the studied compounds in urine of TB patients. Additionally, we conducted a stability study of the anti-TB agents under various pH and temperature conditions to mimic the urine collection process in different settings (peripheral clinics or central laboratories).

The unique eco-environment of the Qinghai-Tibet Plateau breeds abundant microbial resources. In this research, Bacillus amyloliquefaciens GL18, isolated from the rhizosphere of Kobresia myosuroides from an alpine meadow, and the antagonistic activity, bacteriostatic hydrolase activity, and low temperature, salt, and drought resistance of it were determined and analysed. The seedlings of Avena sativa were root-irrigated using bacteria suspensions (cell concentration 1 × 10 7  cfu/mL) of GL18, and the growth-promoting effect of GL18 on it was determined under cold, salt and drought stress, respectively. The whole genome of GL18 was sequenced, and its functional genes were analysed. GL18 presented significant antagonistic activity to Fusarium graminearum, Fusarium acuminatum, Fusarium oxysporum and Aspergillus niger (inhibition zone diameter > 17 mm). Transparent zones formed on four hydrolase detection media, indicating that GL18 secreted cellulase, protease, pectinase and β-1,3-glucanase. GL18 tolerated conditions of 10 °C, 11% NaCl and 15% PEG-6000, presenting cold, salt and drought resistance. GL18 improved the cold, salt and drought tolerance of A. sativa and it showed significant growth effects under different stress. The total length of the GL18 genome was 3,915,550 bp, and the number of coding DNA sequence was 3726. Compared with the clusters of orthologous groups of proteins, gene ontology and kyoto encyclopedia of genes and genomes databases, 3088, 2869 and 2357 functional genes were annotated, respectively. GL18 contained gene clusters related to antibacterial substances, functional genes related to the synthesis of plant growth-promoting substances, and encoding genes related to stress resistance. This study identified an excellent Bacillus strain and provided a theoretical basis for improving stress resistance and promoting the growth of herbages under abiotic stress., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Chemotherapy resistance is one of the main reasons for the poor prognosis of colorectal cancer (CRC). Moreover, dysbiosis of gut bacteria was found to be a specific environmental risk factor. In this study, enrichment of F. nucleatum was elucidated to be significantly associated with CRC recurrence after chemotherapy. Functional experiments showed that F. nucleatum could inhibit pyroptosis induced by chemotherapy drugs, thereby inducing chemoresistance. Furthermore, mechanistic investigation demonstrated that F. nucleatum could regulate the Hippo pathway and promote the expression of BCL2, thereby inhibiting the Caspase-3/GSDME pyroptosis-related pathway induced by chemotherapy drugs and mediating CRC cell chemoresistance. Taken together, these results validated the significant roles of F. nucleatum in CRC chemoresistance, which provided an innovative theoretical basis for the clinical diagnosis and therapy of CRC.

Background: The aim of this study was to investigate the relationship between Age, immunoglobin G (IgG), immunoglobin M (IgM), procalcitonin (PCT), and interleukin-6 (IL6), and the time to clear viral nucleic acids in asymptomatic and mild coronavirus disease 2019 (COVID-19) patients, as well as evaluated the predictive value of these biochemical indicators., Methods: We performed a retrospective analysis on 1,570 individuals who were admitted to Tianjin First Central Hospital and diagnosed with asymptomatic or mild cases. Laboratory data were collected, including age, gender, levels of IgG, IgM, PCT and IL6, as well as results of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleic acid test. These data were statistically analyzed using SPSS software, version 24.0., Results: The results indicated that among mild patients, Age, IgG, and the time to clear viral nucleic acids were higher than asymptomatic patients ( p  < 0.05). And the time to clear viral nucleic acids was significantly correlated with Age, IgG, IgM, PCT, and IL6 ( p  < 0.05), IgG ( r  = -0.445, p  < 0.001) showed moderate correlations. Using logistic regression analysis, we identified older age, high IL6 levels, and low IgG levels were risk factors for nucleic acid clearance exceeding 14 days ( p  < 0.05). When combining these three indicators to predict the probability of nucleic acid clearance exceeding 14 days in the 1,570 patients, the AUROC was found to be 0.727., Conclusion: Age, IgG, and IL6 could potentially serve as useful predictors for nucleic acid clearance exceeding 14 days in asymptomatic and mild COVID-19 patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cao, Xie, Zhou and Mu.)

We report here a dual-nanopore biosensor based on modulation of surface charge density coupled with a microwell array chip for in situ monitoring of ROS secretion from single MCF-7 cells.

Objectives: The purpose of this study was to investigate and compare the effects of 20 ml/kg and 15 ml/kg red blood cell transfusion (RBCT) on cerebral and intestinal tissue oxygenation, the number of administered transfusions, and neonatal complications in premature infants with anemia., Methods: This prospective, randomized, partially blinded observational study investigated anemic neonates of gestational age < 32 weeks (Registration ID: ChiCTR 1,900,026,672). The infants were randomly assigned to receive 15 or 20 ml/kg red blood cell transfusion. Cerebral and intestinal tissue oxygen saturation (cer rSO 2 and int rSO 2 ) were collected 2 h before transfusion, 2, 4, 6, 12, 24, and 48 h after the beginning of transfusion by Near-infrared spectroscopy (NIRS). We also collected vital signs including heart rate (HR), peripheral oxygen saturation (SpO 2 ), and mean arterial blood pressure (MABP) 2 h before infusion, 2 h, and 6 h after the beginning of transfusion. Then we analyzed and compared regional oxygen saturation(rSO 2 ) , fractional tissue oxygen extraction (FTOE), and other outcome readouts (blood transfusion numbers, changes in hematocrit and hemoglobin, hospitalization days, HR, SpO2, MABP, and complications) between the two groups. The intraindividual comparisons of the above readouts before transfusion and those after transfusion were also evaluated within each group., Result: 73 newborns received 20 ml/kg (large volume group) and 78 newborns received 15 ml/kg transfusion (small volume group). There was no significant difference in cer rSO2, int rSO 2 , Cerebral fractional tissue oxygen extraction (cFTOE), and intestinal fractional tissue oxygen extraction (iFTOE) between the two groups. rSO 2, MABP, and SpO 2 increased; HR, cFTOE, and iFTOE decreased following transfusion in both groups. The transfusion number of the large volume group is significantly less than that of the small volume group (1.9 ± 0.3 vs. 2.6 ± 0.9, p < 0.01) and hospitalization days were also less than those in the low volume group (44.3 ± 8.2 vs. 47.6 ± 9.8, p < 0.05). The increases in hematocrit and hemoglobin were higher in the large volume group than those in small volume (hematocrit increment (%),10.7 ± 4.2 vs. 10.1 ± 5.9, p = 0.015; Hb concentration after blood transfusion (g/L) 132.3 ± 11.1 vs. 127.4 ± 15.4, p = 0.028)., Conclusion: After the transfusion, cer rSO2 and int rSO 2 increased significantly, FTOE decreased and vital signs improved in both the 15 ml/kg and 20 ml/kg groups, and these changes were not significantly different between the two groups. However, the larger group showed a more pronounced increase in hematocrit and hemoglobin, a reduction in the total number of transfusions, and a shorter duration of hospitalization after transfusion in preterm infants without increasing complications., Competing Interests: Conflicts of interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The purposes of this study were to develop and validate a nomogram for predicting postoperative transient neurological dysfunctions (TND) in patients with acute type A aortic dissection (AAAD) who underwent modified triple-branched stent graft implantation. This retrospective study developed a nomogram-based model in a consecutive cohort of 146 patients. Patient characteristics, preoperative clinical indices, and operative data were analyzed. Univariate and multivariable analyses were applied to identify the most useful predictive variables for constructing the nomogram. Discrimination and the calibration of the model was evaluated through the receiver operating characteristic curve (ROC), the Hosmer-Lemeshow goodness-of-fit test and the decision curve analysis (DCA). At the same time, to identify and compare long-term cumulative survival rate, Kaplan-Meier survival curve was plotted. The incidence rate of postoperative TND observed in our cohort were 40.9%. Supra-aortic dissection with or without thrombosis, creatinine >115 μmol and albumin <39.7 g/L, selective antegrade cerebral perfusion (SACP) time >7 min and total operation time >303 min, were confirmed as independent predictors that enhanced the likelihood of TND. Internal validation showed good discrimination of the model with under the ROC curve (AUC) of 0.818 and good calibration (Hosmer-Lemeshow test, p > .05). DCA revealed that the nomogram was clinically useful. In the long-term survival there was no significant difference between patients with or without TND history. The results showed the predict model based on readily available predictors has sufficient validity to identify TND risk in this population, that maybe useful for clinical decision-making., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Locoregional radiotherapy added to chemotherapy has significantly improved survival in de novo metastatic nasopharyngeal carcinoma (mNPC). However, only 54% of de novo mNPC patients who received sequential chemoradiotherapy have complete or partial response 3 months after radiotherapy. This Simon's optimal two-stage design phase II study (NCT04398056) investigates whether PD-1 inhibitor could improve tumor control in combination with chemoradiation. The primary endpoint is objective response rate (ORR) at 3 months after radiotherapy. Twenty-two patients with primary mNPC are enrolled. The ORR at 3 months after radiotherapy is 81.8% (22.7% complete response, n = 5; 59.1% partial response, n = 13), and the disease control rate is 81.8%. The 3-year progression-free survival (PFS) rate is 44.9% (95% confidence interval 26.4%-76.3%). Fifteen patients (68.2%) experienced grade 3-4 adverse events. Patients with high baseline plasma Epstein-Barr virus DNA copy number (>10 4 cps/mL) show worse PFS. Addition of toripalimab to sequential chemoradiotherapy suggests promising tumor response in patients with primary mNPC., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Pulmonary artery smooth muscle cells (PASMCs) phenotypic switching and pulmonary artery endothelial cells (PAECs) endothelial-mesenchymal transition (EndMT) are important in promoting pulmonary hypertension (PH)-pulmonary vascular remodeling (PVR). Resveratrol can efficiently inhibit the proliferation of PASMCs, but its application is limited due to its low bioavailability and solubility. In this study, we modified resveratrol to assess the role of A ring N(CH 3 ) 2 -based derivatives of resveratrol (Res4) in PVR-PASMCs phenotypic switching and PVR-PAECs EndMT. Chemical methods were used for the preparation of Res4; NMRS and HPLC were used to authenticate Res4. Mice developed PVR after 4 weeks of hypoxia (10% O 2 ). Res4 (50 mg/kg/d) attenuated right ventricular systolic pressure, right ventricular hypertrophy, and PVR. PASMCs developed phenotypic switching and PAECs developed EndMT after 2 days of hypoxia (3% O 2 ). Res4 (10 μM) could inhibit PASMCs and PAECs viability. Res4 could decrease proliferating cell nuclear antigen (PCNA) and osteopontin (OPN) expression, and increase α-smooth muscle actin (α-SMA) and vimentin expression in PASMCs. It could also decrease PCNA, α-SMA, vimentin expression and increase platelet endothelial cell adhesion molecule (CD31) expression in PAECs. Notably, Res4 inhibited the phosphorylation levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated protein kinase (ERK), Jun-N-terminal kinase (JNK), and p38 kinase in hypoxia-treated PASMCs and PAECs, indicating MAPK pathway may be involved in Res4-induced inhibition of PASMCs phenotypic switching and PAECs EndMT. Our data demonstrated that Res4 exerts antiproliferative effects by regulating PASMCs phenotypic switching and PAECs EndMT. Res4 may be potentially used as a drug against PH-PVR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Variable pharmacokinetics of rifampin in tuberculosis (TB) treatment can lead to poor outcomes. Urine spectrophotometry is simpler and more accessible than recommended serum-based drug monitoring, but its optimal efficacy in predicting serum rifampin underexposure in adults with TB remains uncertain. Adult TB patients in New Jersey and Virginia receiving rifampin-containing regimens were enrolled. Serum and urine samples were collected over 24 h. Rifampin serum concentrations were measured using validated liquid chromatography-tandem mass spectrometry, and total exposure (area under the concentration-time curve) over 24 h (AUC 0-24 ) was determined through noncompartmental analysis. The Sunahara method was used to extract total rifamycins, and rifampin urine excretion was measured by spectrophotometry. An analysis of 58 eligible participants, including 15 (26%) with type 2 diabetes mellitus, demonstrated that urine spectrophotometry accurately identified subtarget rifampin AUC 0-24 at 0-4, 0-8, and 0-24 h. The area under the receiver operator characteristic curve (AUC ROC) values were 0.80 (95% CI 0.67-0.90), 0.84 (95% CI 0.72-0.94), and 0.83 (95% CI 0.72-0.93), respectively. These values were comparable to the AUC ROC of 2 h serum concentrations commonly used for therapeutic monitoring (0.82 [95% CI 0.71-0.92], P = 0.6). Diabetes status did not significantly affect the AUC ROCs for urine in predicting subtarget rifampin serum exposure ( P = 0.67-0.92). Spectrophotometric measurement of urine rifampin excretion within the first 4 or 8 h after dosing is a simple and cost-effective test that accurately predicts rifampin underexposure. This test provides critical information for optimizing tuberculosis treatment outcomes by facilitating appropriate dose adjustments., Competing Interests: The authors declare no conflict of interest.

Objective: The c-Jun N-terminal kinases (JNK) signaling pathway may be involved in the regulation of osteoclast development. The purpose of this investigation was to investigate whether SB600125, a JNK inhibitor, could attenuate titanium-particle-induced inflammatory osteolysis in vivo., Materials and Methods: A total of 45 mice were randomly divided into a Sham group, a Titanium group, and a Titanium + JNK inhibitor group, 15 mice per group. After establishing an air pouch bone graft model, we injected phosphate-buffered saline (PBS), titanium particles, or titanium particles + JNK inhibitor into the air pouch of the three groups. The pouch membranes containing bone implants were taken for morphological and molecular analysis 14 days after the mice were sacrificed., Results: General morphological structure observation results, Hematoxylin and Eosin (H&E)-Stained Sections, anti-tartaric acid phosphatase (TRAP) staining, and the transmission electron microscope showed that SB600125, by inhibiting the expression of JNK, attenuated titanium particle-induced inflammatory osteolysis (p<0.05). Immunohistochemical appearance results and reverse transcription-polymerase chain reaction (RT-PCR) results showed SB600125 reduced expression of IL-6, and TNF-α in osteolytic sites stimulated with wear debris (p<0.05). The Western blot results showed the expression of the p-JNK protein in the titanium particle + SB600125 group was significantly reduced compared to the titanium particle stimulation group (p<0.05)., Conclusions: Interfering with the JNK signaling pathway may be beneficial in reducing osteolysis, providing a therapeutic target for preventing and treating aseptic loosening caused by debris-induced inflammatory osteolysis.