1.Expert consensus on clinical application of parenteral direct thrombin inhibitors in perioperative period
Mingyu JIANG ; Yuan BIAN ; Lizhu HAN ; Qinan YIN ; Fengjiao KANG ; Anhua WEI ; Danjie ZHAO ; Lin WANG ; Ying SHAO ; Li TANG ; Yi WANG ; Shuhong LIANG ; Huijuan LIU ; Guirong XIAO ; Yue LI
China Pharmacy 2026;37(6):689-699
OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors (DTIs) in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital (the Affiliated Hospital of UESTC), a multidisciplinary working group was established. Through literature review and the Delphi method, clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework; systematic searches were conducted in CNKI, Medline, Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment,Development and Evaluation (GRADE) approach, and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations (each with an expert consensus rate exceeding 90%) on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection, dosing ranges, key monitoring points, and safety management strategies for parenteral DTIs in various scenarios, including the perioperative period of ventricular assist device implantation, the perioperative period of cardiac surgery, perioperative patients with lower-extremity atherosclerotic disease, the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome, the perioperative period of carotid artery stenting in patients with carotid stenosis, the perioperative period of patients with right heart thrombosis, and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition, warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus, which is formulated based on the best available evidence, provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.
2.Relationship between Alzheimer's disease and sarcopenia and body mass index:analysis of GWAS datasets for European populations
Qiwang HE ; Bo CHEN ; Fuchao LIANG ; Zewei KANG ; Yuan ZHOU ; Anxu JI ; Xialin TANG
Chinese Journal of Tissue Engineering Research 2026;30(4):1036-1046
BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95%confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95%Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95%Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95%Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95%Cl,0.969-0.980;P<0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25%and 32.11%,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.
3.Relationship between Alzheimer's disease and sarcopenia and body mass index:analysis of GWAS datasets for European populations
Qiwang HE ; Bo CHEN ; Fuchao LIANG ; Zewei KANG ; Yuan ZHOU ; Anxu JI ; Xialin TANG
Chinese Journal of Tissue Engineering Research 2026;30(4):1036-1046
BACKGROUND:Alzheimer's disease has been associated with sarcopenia,but a causal relationship has not been established.Exploring the causal relationship between the two most common disability-burdening diseases in the aging population-Alzheimer's disease and sarcopenia-and their potential mediating factors holds certain implications for further alleviating the healthcare costs and socioeconomic burden for older adults in China.OBJECTIVE:To explore the potential causal relationship between Alzheimer's disease and sarcopenia in the general population using a Mendelian randomization study and to explore the role of body mass index in this context.METHODS:Two-sample Mendelian randomization analysis based on published genome-wide association studies(GWAS)were used to infer causality,and univariate Mendelian randomization and mediation analyses were used in the study design.Through the Integrative Epidemiology Unit(IEU)database,ieu-b-2 was selected as the Alzheimer's disease dataset(sample size:63 926),ieu-b-4816 as the body mass index dataset(99 998),ebi-a-GCST90000027 as the appendicular lean mass dataset(244 730),ukb-b-7478 as the left hand grip strength dataset(461 026),ukb-b-10215 as the right hand grip strength dataset(461 089)and ukb-b-4711 as the walking pace dataset(459 915).Inverse-variance weighting was used as the primary analysis method,and the results were validated by pleiotropy and heterogeneity analysis.The Steiger Directionality Test was performed to validate the reasonableness of the causal direction.RESULTS AND CONCLUSION:(1)The Mendelian randomization analyses provided evidence that Alzheimer's disease predicted the risk of appendicular lean mass[odds ratio(OR)=1.009;95%confidence interval(Cl),1.001-1.017;P=0.023),and walking pace(OR=1.010;95%Cl,1.003-1.017;P=0.008).No correlation with hand grip strength was observed.(2)Alzheimer's disease was negatively correlated with body mass index(OR=0.893;95%Cl,0.811-0.984;P=0.022);body mass index was positively correlated with appendicular lean mass(OR=1.084;95%Cl,1.031-1.141;P=0.002)and negatively correlated with walking pace(OR=0.975;95%Cl,0.969-0.980;P<0.001).(3)Mediation analyses showed that the causal relationship between Alzheimer's disease and appendicular lean mass and walking pace was partially mediated by body mass index,with the proportion of mediations being 50.25%and 32.11%,respectively.(4)The results of this study suggest that based on large-scale population studies,genetic prediction of Alzheimer's disease is a potential risk factor for sarcopenia,in which body mass index plays an important mediating role.This suggests that in clinical practice,attention should be paid to the muscle condition of patients with Alzheimer's disease,and weight management should be implemented,as maintaining a body mass index within the normal high range may have a preventive effect on the occurrence of sarcopenia in patients with Alzheimer's disease.However,further research is needed to verify the applicability of this conclusion to other ethnic groups.This study utilized an international public database for analysis,providing a reference for research on the correlation between Alzheimer's disease and sarcopenia in the Chinese population.It also highlights the significant mediating role of body mass index,offering insights for further prevention and treatment of sarcopenia among Chinese individuals.
4.Exploring Mechanism of Xiaojinwan-containing Serum in Inhibiting Breast Cancer Cells Based on Wnt/β-catenin Signaling Pathway
Hongdi TANG ; Xiaobo JIN ; Chen GAO ; Hongkai LI ; Zhiming LI ; Lu YAO ; Fengli SONG ; Ning KANG ; Wenwen WANG ; Ying SUN ; Zhibin WANG ; Tong LI ; Yingli ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(17):13-22
ObjectiveTo investigate the role and underlying mechanism of the Wnt/β-catenin signaling pathway in the process of Xiaojinwan (XJW)-containing serum interfering with endothelial-mesenchymal transition (EMT) in human breast cancer MDA-MB-231 cells. MethodsXJW-containing serum was prepared by intragastric administration of XJW (4 g·kg-1) to SD rats. MDA-MB-231 cells were cultured in vitro. β-Catenin overexpression and knockdown plasmids were constructed and transfected into MDA-MB-231 cells. The optimal XJW-containing serum (4 g·kg-1) according to previous studies was used for β-catenin intervention and overexpression experiments. The groups for intervention/overexpression experiments included intervention/overexpression blank group, β-catenin intervention/overexpression group, intervention/overexpression blank + XJW group, and β-catenin intervention/overexpression + XJW group. Cell morphology was observed under a microscope. Flow cytometry was used to detect and record apoptosis rates. Western blot was performed to measure apoptosis-related proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and active-Caspase-3] and EMT-related proteins (E-cadherin, N-cadherin, and vimentin). Real-time polymerase chain reaction (Real-time PCR) was used to detect β-catenin mRNA expression levels in different groups. ResultsIntervention experiment results showed that compared with the intervention blank group, the β-catenin intervention group and the intervention blank + XJW group showed increased apoptosis rates (P<0.05, P<0.01), elevated protein levels of Bax, active Caspase-3, and E-cadherin (P<0.05, P<0.01), and decreased protein levels of Bcl-2 and Vimentin (P<0.05, P<0.01). β-catenin mRNA expression was reduced in the β-catenin intervention group (P<0.05, 0.63 ± 0.15) and the intervention blank + XJW group (P<0.05, 0.79 ± 0.33). Compared with the β-catenin intervention group, the β-catenin intervention + XJW group exhibited an increased apoptosis rate (P<0.01), elevated Bax and active Caspase-3 protein levels (P<0.05, P<0.01), and decreased Bcl-2, N-cadherin, and Vimentin protein levels (P<0.05). β-catenin mRNA expression was further reduced in the β-catenin intervention + XJW group (P<0.01, 0.22 ± 0.08). Compared with the intervention blank + XJW group, the β-catenin intervention + XJW group showed an increased apoptosis rate (P<0.01), elevated Bax, active Caspase-3, and E-cadherin protein levels (P<0.05, P<0.01), and decreased Bcl-2, N-cadherin, and vimentin protein levels (P<0.05, P<0.01). β-catenin mRNA expression was also reduced (P<0.05). Overexpression experiment results showed that compared with the overexpression blank group, the β-catenin overexpression group exhibited a reduced apoptosis rate (P<0.01), while the overexpression blank + XJW group showed an increased apoptosis rate (P<0.05). In the β-catenin overexpression and β-catenin overexpression + XJW groups, Bax and E-cadherin protein levels decreased (P<0.05, P<0.01), while Bcl-2, N-cadherin, and vimentin levels increased (P<0.05). In the overexpression blank + XJW group, Bax and E-cadherin levels increased (P<0.05, P<0.01), while Bcl-2, N-cadherin, and vimentin levels decreased (P<0.05, P<0.01). β-catenin mRNA expression increased in the β-catenin overexpression group (P<0.01, 7.26 ± 1.03) but decreased in the overexpression blank + XJW group (P<0.05, 0.73 ± 0.14). Compared with the β-catenin overexpression group, the β-catenin overexpression + XJW group showed an increased apoptosis rate (P<0.01), elevated Bax and E-cadherin levels (P<0.05), and decreased N-cadherin and vimentin levels (P<0.05). β-catenin mRNA expression was reduced (P<0.05, 4.65 ± 1.02). Compared with the overexpression blank + XJW group, the β-catenin overexpression + XJW group exhibited a reduced apoptosis rate (P<0.01), decreased Bax and E-cadherin levels (P<0.01), and increased Bcl-2, N-cadherin, and Vimentin levels (P<0.05). β-catenin mRNA expression increased (P<0.01). ConclusionXJW-containing serum inhibits breast cancer cell proliferation by suppressing EMT, which is associated with the regulation of the Wnt/β-catenin pathway.
5.Temporal trends of physical fitness indicators and the relationship to body mass index among college students
TANG Hanchenye,XIAO Kunpeng,WANG Qingran,SHANG Yao,KANG Yiting,WANG Huiling,LIU Changjiang
Chinese Journal of School Health 2026;47(8):1166-1169
Objective:
To explore the temporal variation in physical health status among college students, analyze the correlation and dose response relationship between body mass index (BMI) and physical fitness indicators, so as to provide a scientific basis for physical health intervention among college students in universities.
Methods:
A total of 4 910 freshmen in the 2021 grade at Xi an Jiaotong University were selected. The BMI and changes in five physical fitness indicators (50 meter run, endurance run, standing long jump, sit and reach, and pull up or 1 minute sit up) were continuously assessed during follow up evaluations from 2021 to 2024. One way analysis of variance, generalized estimating equation (GEE), and other statistical methods were used to analyze the trends in temporal variation among the physical fitness indicators as well as the correlation characteristics and dose response relationship between BMI and physical fitness.
Results:
In 2021 the overweight and obesity rates among male freshmen were 20.36 % and 8.62%, respectively, and 12.91% and 2.91% among female freshman, respectively. From 2021 to 2024 the BMI of male and female students showed an upward trend with a significant increase( F =87.29,3.69,both P <0.05). The physical fitness indicators for both male and female students, including the 50 meter run, standing long jump, pull up and 1 minute sit up, first increased and then decreased, the endurance run performance decreased, and the sit and reach performance first decreased and then increased. The GEE model showed that BMI was negatively correlated with the performance of standing long jump, pullup/1 minute sit up, and sit and reach in both male and female students( β =-1.72,-0.34,-0.15;-0.94,-0.26,-0.12), and positively correlated with the time of 50 meter run and endurance run( β =0.05,3.16;0.03,1.86)(all P <0.05). The increase in BMI was associated with physical fitness decline in a non linear dose response relationship, while the sit and reach performance reached a peak at a BMI of approximately 22 kg/m 2, then decreased with the further increase in BMI.
Conclusions
A significant negative correlation is demonstrated between BMI and physical fitness indicators and male students are more sensitive to changes in BMI. College students should be guided to actively manage their weight and attach importance to physical exercise to improve their physical health.
6.Study on the correlation between inflammatory indicators in the hyperacute phase of acute ischemic stroke and early neurological deterioration, syndrome factors, and prognosis
Ligaoge KANG ; Ying GAO ; Jinyue BAI ; Huan TANG ; Hongbo SHEN ; Lei LIU ; Lingbo KONG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):98-107
Objective:
Inflammatory cascade reactions play a crucial role in secondary neuronal injury in acute ischemic stroke (AIS). The aim of this study was to explore the correlations between specific serological indicators, early neurological deterioration (END), disease prognosis, and syndrome factors in AIS based on this injury mechanism.
Methods:
The data for this study were collected from 135 patients with AIS admitted to the emergency department of Fangshan Hospital, Beijing University of Chinese Medicine, within 24 h of onset between November 2019 and May 2021. Among these, 29 patients had complete data and experienced END. Additionally, 9 non-END patients were matched from the remaining 90 patients with complete data, resulting in a total of 38 patients for statistical analysis. Statistical methods, including logistic regression and receiver operating curves, were used to analyze the correlation between serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), and intercellular adhesion molecule-1 (ICAM-1) within 24 h of END onset, disease prognosis, and syndrome factors. Grouping criteria included END occurrence, presence of syndrome elements on the first and third day post-onset, and prognosis at 90 days post-onset.
Results:
All 38 cases had onset time of less than 12 h, and there were no significant differences in age, gender, and onset time between the END and non-END groups. The TNF-α serum level within 24 h of onset was not associated with the occurrence of END but was negatively correlated with all-cause mortality at 90 days [0.1
7.Posterior cranial fossa in- situ floating bone flap osteotomy for the treatment of syndromic craniosynostosis
Meirong TANG ; Xu KANG ; Yunhai SONG ; Pingping GAO ; Zeyang XIA ; Nan BAO
Chinese Journal of Plastic Surgery 2025;41(5):463-472
Objective:To investigate the efficacy of posterior cranial fossa in- situ floating bone flap osteotomy in the treatment of syndromic craniosynostosis(SCS). Methods:The clinical data of SCS children who underwent posterior cranial fossa in- situ floating bone flap osteotomy at the Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine from April 2020 to August 2022 were retrospectively analyzed. The surgical procedures were as follows. The occipital bone was cut into several mosaic bone flaps of varying sizes, without peeling it off the dura, which were left as a small free floating bone flap. The anteroposterior cranial diameter, cranial height, intracranial volume, and degree of improvement in tonsillar herniation and hydrocephalus of the children (hydrocephalus quantification was performed using the ratio of the ventricular diameter to the biparietal diameter)were measured preoperatively, 7 days postoperatively, 3 months postoperatively, and at the last follow-up (at least 12 months after the operation) to evaluate the surgical outcomes. The measurement data of normal distribution were expressed as Mean±SD. The paired t-test was used for comparison within the repeated measurement data groups at the two time points. One-way repeated measures analysis of variance (ANOVA) was performed on the repeated measurement data at multiple time points, and pairwise comparisons in post hoc tests were corrected using the Bonferroni method. Results:A total of 17 pediatric patients with SCS were included, comprising 10 males and 7 females, with ages ranging from 4 to 18 months (mean age: 9.5 months). Among them, 12 patients were complicated with Chiari malformation and hydrocephalus (1 severe case, 8 moderate cases, and 3 mild cases). Postoperative follow-up lasted 12 to 35 months, with an average of 17 months. After surgery, the posterior cranial appearance of the children was enlarged, with increased convexity of the occiput and a full contour. At the last follow-up, the middle cranial height [(107.80±10.72) mm vs. (102.82±10.09) mm, P<0.05], the posterior cranial height [(124.91±10.40) mm vs. (107.58±13.46) mm, P<0.01] and anteroposterior diameter [(153.30±11.26) mm vs. (123.64±17.44) mm, P<0.01] as well as the intracranial volume [(1 317.92±225.77) cm 3 vs. (1 014.93±231.81) cm 3,P<0.01] were increased compared with the preoperative period, and the average improvement rate of intracranial volume was 37.0% (18.1%-79.2%). Among the 12 cases of tonsillar herniation, 7 cases had improvement. Moreover, all the 12 cases of hydrocephalus witnessed a mitigation in severity, from (46.33±9.34)% preoperatively to (35.24±9.88)% postoperatively, with a statistically significant difference ( P<0.01). Conclusion:Posterior cranial fossa in- situ floating bone flap osteotomy can effectively improve the appearance of patients with SCS, increase the intracranial volume, relieve the degree of hydrocephalus, and reduce the intracranial pressure.
8.The value of a nomogram based on multi-parameter MRI for predicting the risk of postoperative recurrence in hormone receptor positive breast cancer
Di KANG ; Lihua ZHANG ; Weixia TANG ; Jinfeng QIAN ; Tianle WANG ; Meihong SHENG
Chinese Journal of Radiology 2025;59(10):1155-1162
Objective:To investigate the value of a multi-parameter MRI nomogram model in evaluating the recurrence risk of hormone receptor (HR)-positive breast cancer.Methods:This study was a retrospective cross-sectional study. A retrospective analysis was conducted on the clinicopathological data (age, menopausal status, axillary lymph node metastasis, etc.) and imaging data of 220 patients with HR-positive breast cancer who underwent breast MRI examination and were pathologically confirmed at the Second Affiliated Hospital of Nantong University from January 2018 to December 2023. All patients underwent preoperative MRI examinations. Their MRI features were analyzed, and the maximum diameter of the lesion and the apparent diffusion coefficient (ADC) value were measured. Finally, the clinical treatment score (CTS5 score) after 5 years was calculated, and all patients were divided into a low recurrence risk (CTS5 score 3.13 points) and a medium to high recurrence risk (CTS5 score≥3.13 points) group. The patients were followed up through the electronic medical record system or by phone until December 31, 2024 to determine recurrence status. The patients were divided into the recurrence group and the non-recurrence group. The differences in clinicopathological data, MRI features and CTS5 scores between the recurrence group and the non-recurrence group were compared using independent sample t-tests, Mann-Whitney U tests or χ2 tests. Indicators with P0.05 in the univariate analysis were included in the multivariate logistic regression to screen the independent risk factors for predicting the recurrence of HR receptor-positive breast cancer, and a nomogram was constructed to establish the nomogram model. The receiver operating characteristic curves and the area under the curve (AUC) were used to evaluate the efficacy of the nomogram model in predicting the postoperative recurrence risk of patients with HR-positive breast cancer. The variance inflation factor (VIF) was used to evaluate the multicollinearity among independent variables. Calibration curves and decision curve analysis (DCA) were used to assess the fit and net clinical benefit of the nomogram model. Results:Among 220 patients with HR-positive breast cancer, 196 cases were in the non-recurrence group and 24 cases were in the recurrence group. There were statistically significant differences in the maximum diameter of the lesion, axillary lymph node metastasis, ADC value, CTS5 grouping, and CTS5 score between the recurrence group and the non-recurrence group ( P0.05). Multivariate logistic regression analysis showed that the maximum diameter of the lesion ( OR=1.110, 95% CI 1.169-1.503, P0.001), ADC value ( OR=0.993, 95% CI 0.993?0.989, P0.001), and axillary lymph node metastasis ( OR=8.842; 95% CI 2.120?36.884, P=0.003) were independent factors influencing postoperative recurrence in patients with HR-positive breast cancer, and a nomogram model was constructed based on this. VIF analysis showed that no significant multicollinearity was detected among the variables (VIF5). The AUC value of the nomogram model for predicting postoperative recurrence in patients with HR-positive breast cancer was 0.868 (95% CI 0.794-0.942), the sensitivity was 0.875, and the specificity was 0.781. The calibration curve showed that the prediction curve of this model for predicting postoperative recurrence in HR-positive breast cancer patients was basically consistent with the ideal curve trend. DCA showed that this model had a relatively high clinical benefit within the threshold probability range of 0.01% to 90.00%. Conclusion:The nomogram constructed based on multi-parameter MRI features can predict the postoperative recurrence risk of HR-positive breast cancer patients, with good consistency and predictive ability.
9.Distance self-attention and long short-term memory model for predicting X-ray tube arcing in CT equipment
Haopeng ZHOU ; Yuyao TANG ; Changxi WANG ; Kang LI ; Zhenlin LI
Chinese Journal of Medical Imaging Technology 2025;41(4):659-665
Objective To construct a distance self-attention(DSA)and long short-term memory(LSTM)model and observe its value for predicting X-ray tube arcing in CT equipment.Methods CT equipment status data of internet of medical things were collected and preprocessed,then DSA-LSTM model based on model attention(MA)module and nonlinear attenuation distance factor was constructed,and its value for predicting X-ray tube arcing in CT equipment was analyzed compared with other models.Results Compared with other models,DSA-LSTM model had better comprehensive efficiency for predicting X-ray tube arcing in CT equipment.MA module and nonlinear attenuation distance factor could improve the predictive efficiency of DSA-LSTM model,and all included features contributed to the performance of DSA-LSTM model in a certain extent.Conclusion DSA-LSTM model could effectively predict X-ray tube arcing in CT equipment.
10.4-Octyl itaconate inhibits synovitis in the mouse model of post-traumatic osteoarthritis and alleviates pain.
Yu-Zhen TANG ; Wan CHEN ; Bao-Yun XU ; Gang HE ; Xiu-Cheng FAN ; Kang-Lai TANG
Chinese Journal of Traumatology 2025;28(1):50-61
PURPOSE:
To investigate the pathological changes of the synovium in mice with post-traumatic osteoarthritis (PTOA) treated with 4-octyl itaconate (4-OI) and evaluate the therapeutic effects of 4-OI.
METHODS:
In the phenotypic validation experiment, the mice were randomly divided into 3 groups: wild-type (WT) group, sham group, and destabilization of the medial meniscus (DMM) group. Through MRI, micro-CT, and histological analysis, it was determined that the DMM surgery induced a mouse PTOA model with significant signs of synovitis. At 12 weeks post-DMM surgery, synovial tissues from the DMM group and WT group mice were collected for ribonucleic acid sequencing analysis. In the 4-OI treatment experiment, mice were randomly divided into the sham group, DMM group, DMM + 4-OI (50 mg/kg) group, and DMM + 4-OI (100 mg/kg) group. Von Frey tests and open field tests were conducted at intervals during the 12 weeks following the DMM surgery. After 12 weeks of surgery, the efficacy of 4-OI treatment on PTOA in mice was evaluated using MRI, micro-CT, histological analysis, and quantitative real-time polymerase chain reaction. Finally, we utilized network pharmacology analysis to predict the mechanism of 4-OI in treating PTOA synovitis and conducted preliminary validation. Statistical analysis was performed using one-way ANOVA and the Kruskal-Wallis test. Difference was considered statistically significant at p < 0.05.
RESULTS:
The DMM surgery effectively induced a PTOA mouse model, which displayed significant symptoms of synovitis. These symptoms included a notable increase in both the number of calcified tissues and osteophytes (p < 0.001), an enlargement of the calcified meniscus and synovial tissue volume (p < 0.001), and thickening of the synovial lining layer attributable to M1 macrophage accumulation (p = 0.035). Additionally, we observed elevated histological scores for synovitis (p < 0.001). Treatment with 4-OI inhibited the thickening of M1 macrophages in the synovial lining layer of PTOA mice (p < 0.001) and reduced fibrosis in the synovial stroma (p = 0.004). Furthermore, it reduced the histological scores of knee synovitis in PTOA mice (p = 0.006) and improved the inflammatory microenvironment associated with synovitis. Consequently, this treatment alleviated pain in PTOA mice (p < 0.001) and reduced spontaneous activity (p = 0.003). Bioinformatics and network pharmacology analyses indicated that 4-OI may exert its therapeutic effects by inhibiting the differentiation of synovial Th17 cells. Specifically, compared to the lipopolysaccharide stimulation group, 4-OI reduced the levels of positive regulatory factors of Th17 cell differentiation (IL-1: p < 0.001, IL-6: p < 0.001), key effector molecules (IL-17A: p < 0.001, IL-17F: p = 0.004), and downstream effector molecules in the IL-17 signaling pathway (CCL2: p < 0.001, MMP13: p < 0.001).
CONCLUSION
4-OI is effective in inhibiting synovitis in PTOA, thereby alleviating the associated painful symptoms.
Animals
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Synovitis/etiology*
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Mice
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Osteoarthritis/etiology*
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Disease Models, Animal
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Male
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Succinates/pharmacology*
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Mice, Inbred C57BL
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X-Ray Microtomography


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