1.Inhibitory effects of different concentrations of auranofin on M1 macrophage function and its therapeutic potential in diabetic wound healing
Hongfei PAN ; Zhenbing ZHUANG ; Baiyun XU ; Zhangyang YANG ; Kairui LIN ; Bingqing ZHAN ; Jinghan LAN ; Heng GAO ; Nanbo ZHANG ; Jiayu LIN
Chinese Journal of Tissue Engineering Research 2026;30(6):1390-1397
BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.
2.Inhibitory effects of different concentrations of auranofin on M1 macrophage function and its therapeutic potential in diabetic wound healing
Hongfei PAN ; Zhenbing ZHUANG ; Baiyun XU ; Zhangyang YANG ; Kairui LIN ; Bingqing ZHAN ; Jinghan LAN ; Heng GAO ; Nanbo ZHANG ; Jiayu LIN
Chinese Journal of Tissue Engineering Research 2026;30(6):1390-1397
BACKGROUND:During diabetic wound healing,the sustained activation of M1 macrophages exacerbates the inflammatory response and hinders wound repair.Auranofin,an anti-inflammatory drug,has not been clearly studied for its effects on M1 macrophages and its potential role in diabetic wound healing.OBJECTIVE:To investigate the effects of different concentrations of auranofin on the biological function of M1 macrophages and evaluate its potential application in diabetic wound healing.METHODS:RAW264.7 and THP-1 cells were used as research models.M1 polarization was induced using different concentrations of interferon-γ and lipopolysaccharide.M1 macrophages were treated with 1 and 2 μmol/L auranofin.Cell counting kit-8 assay was used to evaluate the effect of auranofin on cell viability.Quantitative real-time PCR was performed to detect mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.ELISA was employed to measure the levels of interleukin-1β,interleukin-6,and tumor necrosis factor-α in the supernatant.Western blot analysis was used to assess the expression of nuclear factor-κB(p65),phosphorylated mitogen-activated protein kinases(MAPK),and total MAPK proteins.Additionally,6-8-week-old male C57BL/6J and db/db diabetic mice were used for wound healing experiments,with the mice divided into C57 control,db/db control and auranofin treatment groups,each containing six animals.Dorsal skin defect modeling and treatment with intraperitoneal injection of auranofin were performed to observe wound healing in mice.RESULTS AND CONCLUSION:(1)Cell experiments showed that co-treatment with interferon-y(10 ng/mL)and lipopolysaccharide(100 ng/mL)significantly induced M1 polarization in RAW264.7 and THP-1 cells,resulting in increased mRNA expression of interleukin-1β,interleukin-6,and tumor necrosis factor-α.Treatment with auranofin(1 and 2 μmol/L)reduced the mRNA expression of these inflammatory factors in the cells and inhibited the secretion of inflammatory factors in the cell supernatant.(2)Auranofin treatment significantly suppressed the activation of nuclear factor-κB(p65)and phosphorylated MAPK signaling pathways.(3)Animal experiments showed that auranofin promoted wound healing in db/db diabetic mice,suggesting that auranofin has strong anti-inflammatory effects and may facilitate the healing of wounds in diabetic mice.
3.The Specificity of Electroacupuncture at Different Acupoints in Promoting Cerebrospinal Fluid Flow in Mice
Yu SHI ; Qian HUA ; Tian-Tian PENG ; Yu-Xin NIE ; Zhao-Heng LIU ; Chen-Geng DENG ; Xu WANG
Progress in Biochemistry and Biophysics 2026;53(5):1154-1164
ObjectiveCerebrospinal fluid (CSF) plays a crucial role in maintaining the homeostasis of the central nervous system (CNS). CSF rapidly exchanges with interstitial fluid (ISF) via the glymphatic system within the brain parenchyma. CSF-ISF circulation and its associated mechanisms are often referred to as the brain lymphatic system. This system is connected directly to meningeal lymphatic vessels (mLVs), jointly performing the function of clearing metabolic waste from the CNS. Emerging evidence indicates that this system is closely associated with the onset and progression of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Importantly, abnormal CSF circulation is not only a downstream consequence of AD pathology, but also a risk factor. In AD, the dynamics of CSF flow within the CNS are diminished, immune dysregulation occurs, and this may increase the risk of AD by exacerbating the burden of amyloid β-protein (Aβ). In the mouse model of AD, impaired CSF flow compromises this clearance function, leading to cognitive deficits. Clinically, acupuncture at cognition-related acupoints is commonly used for the prevention and treatment of AD. However, whether its therapeutic effects are mediated through the modulation of CSF dynamics remains unclear. This study aimed to evaluate the impact of acupuncture on CSF flow and investigate its acupoint specificity. MethodsMice were randomly assigned to experimental groups for the different electroacupuncture groups with the following acupoints: Baihui point (GV 20), Ear point, Neiguan point (PC 6), and Tianshu point (ST 25). Wild-type mice on a C57BL/6J background were used as controls. Fluorescent tracer was injected into the cisterna magna to label CSF flow. Fluorescence imaging was employed to assess the distribution of CSF within the brain before and after acupuncture stimulation. ResultsFollowing tracer injection into the cisterna magna, fluorescence signals rapidly reached the cerebellum and medulla—the regions closest to the injection site. Fluorescence intensity was higher in ventral brain regions compared to dorsal regions, likely due to greater vascular density in ventral areas facilitating CSF-ISF exchange. Electroacupuncture at the GV 20 produced the most pronounced enhancement of CSF across the whole brain, while stimulation at the ST 25 primarily augmented flow within subcortical regions. In contrast, electroacupuncture at the Ear point or the PC 6 had no observable effect on CSF in mice. ConclusionElectroacupuncture promotes CSF flow into the brain parenchyma in an acupoint-specific manner, with GV 20 exhibiting the most pronounced enhancement of CSF dynamics. These findings suggest that acupuncture-mediated facilitation of CSF flow may represent a potential therapeutic strategy for preventing or delaying age-related cognitive decline.
4.The Specificity of Electroacupuncture at Different Acupoints in Promoting Cerebrospinal Fluid Flow in Mice
Yu SHI ; Qian HUA ; Tian-Tian PENG ; Yu-Xin NIE ; Zhao-Heng LIU ; Chen-Geng DENG ; Xu WANG
Progress in Biochemistry and Biophysics 2026;53(5):1154-1164
ObjectiveCerebrospinal fluid (CSF) plays a crucial role in maintaining the homeostasis of the central nervous system (CNS). CSF rapidly exchanges with interstitial fluid (ISF) via the glymphatic system within the brain parenchyma. CSF-ISF circulation and its associated mechanisms are often referred to as the brain lymphatic system. This system is connected directly to meningeal lymphatic vessels (mLVs), jointly performing the function of clearing metabolic waste from the CNS. Emerging evidence indicates that this system is closely associated with the onset and progression of neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD). Importantly, abnormal CSF circulation is not only a downstream consequence of AD pathology, but also a risk factor. In AD, the dynamics of CSF flow within the CNS are diminished, immune dysregulation occurs, and this may increase the risk of AD by exacerbating the burden of amyloid β-protein (Aβ). In the mouse model of AD, impaired CSF flow compromises this clearance function, leading to cognitive deficits. Clinically, acupuncture at cognition-related acupoints is commonly used for the prevention and treatment of AD. However, whether its therapeutic effects are mediated through the modulation of CSF dynamics remains unclear. This study aimed to evaluate the impact of acupuncture on CSF flow and investigate its acupoint specificity. MethodsMice were randomly assigned to experimental groups for the different electroacupuncture groups with the following acupoints: Baihui point (GV 20), Ear point, Neiguan point (PC 6), and Tianshu point (ST 25). Wild-type mice on a C57BL/6J background were used as controls. Fluorescent tracer was injected into the cisterna magna to label CSF flow. Fluorescence imaging was employed to assess the distribution of CSF within the brain before and after acupuncture stimulation. ResultsFollowing tracer injection into the cisterna magna, fluorescence signals rapidly reached the cerebellum and medulla—the regions closest to the injection site. Fluorescence intensity was higher in ventral brain regions compared to dorsal regions, likely due to greater vascular density in ventral areas facilitating CSF-ISF exchange. Electroacupuncture at the GV 20 produced the most pronounced enhancement of CSF across the whole brain, while stimulation at the ST 25 primarily augmented flow within subcortical regions. In contrast, electroacupuncture at the Ear point or the PC 6 had no observable effect on CSF in mice. ConclusionElectroacupuncture promotes CSF flow into the brain parenchyma in an acupoint-specific manner, with GV 20 exhibiting the most pronounced enhancement of CSF dynamics. These findings suggest that acupuncture-mediated facilitation of CSF flow may represent a potential therapeutic strategy for preventing or delaying age-related cognitive decline.
5.Clinical observation of pramipexole combined with levodopa-benserazide in the treatment of Parkinson’s disease
Heng XU ; Chengrong YE ; Chunming XIE
China Pharmacy 2025;36(5):584-588
OBJECTIVE To investigate the clinical efficacy of pramipexole combined with levodopa-benserazide in the treatment of Parkinson’s disease (PD). METHODS A total of 108 PD patients treated at the Fifth People’s Hospital of Wuhu City from January 1, 2021, to February 28, 2023, were randomly divided into observation group and control group, with 54 cases in each group. Patients in the control group were administered levodopa-benserazide (initial dose of 62.5 mg per dose), three times daily; after one month, the dose was increased to 250 mg per dose, four times daily. Patients in the observation group received the same treatment as the control group, with the addition of pramipexole (initial dose of 0.25 mg per dose) orally twice daily on an empty stomach; after 14 days, the dose was increased to 0.25 mg per dose, three times daily. Both groups were treated for 3 months. The short-term efficacy, safety and long-term prognosis of the two groups were compared. RESULTS After treatment, the observation group had significantly lower scores on the Unified Parkinson’s Disease Rating Scale part Ⅲ (UPDRS-Ⅲ), the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), and the Parkinson’s Disease Questionnaire-39( PDQ- 39) compared to the control group; in contrast, the observation group had higher scores on the Montreal Cognitive Assessment (MoCA) scale, the Mini-mental State Examination (MMSE) scale, the Mattis Dementia Rating Scale (DRS), and the Quality of Life (QOL) scale (P<0.05). Both groups showed a significant reduction in UPDRS-Ⅲ and PDQ-39 scores, and a significant increase in DRS scores compared to baseline (P<0.05). However, only the observation group showed a significant increase in MoCA scale, MMSE scale, and QOL scores, and a significant decrease in HAMD and HAMA scores compared to baseline (P< 0.05). The total incidence of adverse drug reactions in both groups was not significantly different (P>0.05). The 12 months follow-up results showed that the incidence of dementia and mortality rates in the observation group were significantly lower than the control group (P<0.05). CONCLUSIONS Pramipexole combined with levodopa-benserazide significantly improves motor function, cognitive function, quality of life and symptoms of depression and anxiety in PD patients, and may reduce the long-term risk of dementia and mortality in these patients.
6.Quality inspection of ultrasound soft tissue cutting hemostatic equipment
Jing HUANG ; Qi-di SUN ; Ao-wen DUAN ; Li XU ; Heng-yu LONG ; Hai-jiang ZHU ; He-hua ZHANG
Chinese Medical Equipment Journal 2025;46(10):49-53
Objective To carry out quality inspection of the ultrasound soft tissue cutting hemostatic equipment to ensure its safety and effectiveness.Methods Five brands of ultrasound soft tissue cutting hemostatic equipment were selected and noted as test equipment A,test equipment B,test equipment C,test equipment D and test equipment E,which underwent quality inspection in terms of tip main amplitude,tip lateral amplitude,tip vibration frequency,excitation frequency,static electrical power and contact current based on YY/T 0644-2008 Ultrasonics-surgical systems—Measurement and declaration of the basic output characteristics,YY/T 1750-2020 Ultrasonic surgical equipmetn for soft tissue excision and hemostasia and GB 9706.1-2020 Medical electrical equipment—Part 1:General requirements for basic safety and essential performance.Results The test data of the five brands in terms of tip main amplitude,tip lateral amplitude,tip vibration frequency,excitation frequency,static electrical power and contact current met the technical requirements of YY/T 0644-2008,YY/T 1750-2020,GB 9706.1-2020.Conclusion The quality inspection of the ultrasound soft tissue cutting hemostatic equipment contributes to enhancing the accuracy and stability of the equipment and decreasing the risk during its clinical application.[Chinese Medical Equipment Journal,2025,46(10):49-53]
7.Clinical study on the effect of brain-computer interface robot combined with task-oriented training on hand dysfunction after stroke
Han QIN ; Yongmei ZHU ; Qianhui TIAN ; Tianning ZHANG ; Shiwei XU ; Xiaoyan ZHAO ; Heng ZHANG ; Xuan SUN ; Hui ZHAO
Chinese Journal of Cerebrovascular Diseases 2025;22(9):612-621
Objective To observe the impact of brain-computer interface(BCI)robot combined with task-oriented training(TOT)on hand function and activities of daily living in stroke patients.Methods A total of 40 patients with subacute stroke who were hospitalized in the Department of Rehabilitation Medicine of Anhui No.2 Province People's Hospital from December 2022 to December 2024 were prospectively and consecutively included in this study.The stroke patients were randomly assigned to the experimental group and the control group using the random number table method,with 20 cases in each group.Baseline data were collected from all patients,including gender,age,personal history(smoking,drinking),past medical history(hypertension,diabetes),stroke type(hemorrhagic stroke,ischemic stroke),hemiplegia side(left,right),disease course,stroke location(basal ganglia,internal capsule),and admission assessment indicators(including kinesthetic and visual imagery questionnaire[KVIQ-20]score,mini-mental state examination[MMSE]score and National Institutes of Health stroke scale[NIHSS]score).Both groups of patients received conventional rehabilitation training and TOT.The experimental group then underwent BCI robot training combined with TOT on this basis.Both groups received treatments for 4 weeks,and the upper limb and hand functions of all patients were evaluated using the Fugl-Meyer upper extremity function assessment scale(FMA-UE),the wrist-hand part of the FMA-UE scale(FMA-WH),the Wolf motor function test(WMFT),and the modified Ashworth scale(MAS)before and after the treatment;the hand function related part(feeding[10 score],bathing[5 score],dressing[10 score],grooming[5 score],and toilet using[10 score])of modified Barthel index(MBI)was used to assess the patients'hand dexterity to perform daily activities.Results(1)No statistically significant differences were found in the baseline data between the two groups of patients(all P>0.05).(2)Before treatment,the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI in the experimental group were(18.75±7.38),(2.95±1.54),(26.90±8.69),(1.10±0.66),and(15.45±1.82)respectively,while those in the control group were(15.90±5.39),(2.25±1.12),(24.15±6.78),(1.25±0.60),and(15.65±3.12)respectively.There were no statistically significant differences in the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI between the two groups before treatment(all P>0.05).After 4 weeks of treatment,the scores of FMA-UE,FMA-WH,WMFT,MAS and hand function related score of MBI in the experimental group were(27.10±7.76),(5.75±2.97),(40.85±10.19),(0.73±0.57),and(21.15±2.66)respectively,while those in the control group were(21.25±5.29),(4.00±1.49),(31.85±7.60),(0.73±0.64),and(17.40±3.14)respectively.The time main effects(Ftime values were 925.061,138.138,624.635 and 405.986 respectively,all P<0.01),group main effects(Fgroup values were 4.460,4.562,5.011 and 4.411 respectively,all P<0.05),and the interaction effects of time and group(Ftime×group values were 44.358,7.356,52.506 and 114.128 respectively,all P<0.05)of FMA-UE,FMA-WH,WMFT and hand function related score of MBI scores were all significant.The time main effect of MAS scores was significant(Ftime value was 59.478,P<0.01),while the group main effect(Fgroup value was 0.162,P>0.05),the interaction effects of time and group(Ftime×group value was 1.652,P>0.05)were not significant.Conclusion The combined task-oriented training with BCI robots can improve the upper limb and hand functions of stroke patients,enhance their ability to perform daily activities,and the effect is superior to that of single task-oriented training.
8.Feasibility study on the construction of predictive models of knee joint cartilage thickness
Zhi-ming CHENG ; Zhong-hua XU ; Xiao-jun MAN ; Yu-heng LI ; Zai-yang LIU ; Yuan ZHANG
Journal of Regional Anatomy and Operative Surgery 2025;34(7):563-569
Objective To determine the knee joint cartilage thickness using different methods and explore the feasibility of mathematical statistical models of dataset for the prediction of cartilage thickness.Methods A total of 304 patients diagnosed as knee osteoarthritis(OA)combined with varus deformity and undergoing unilateral total knee arthroplasty at the Second Affiliated Hospital of Army Medical University from March 2023 to March 2024 were selected for the study.All patients had complete preoperative and postoperative clinical data.The healthy cartilage at four anatomical sites of patients,including the distal femur lateral condyle,lateral tibial plateau,posterior medial femoral condyle,and posterior lateral femoral condyle were selected,and the knee joint cartilage thickness was determined based on preoperative MRI analysis,robotic navigation system tracing,tissue section of surgical specimen and digital vernier caliper.The baseline indicators of demographics,disease and imaging ffor patients were collected to construct a dataset,and four models of linear regression analysis,principal component analysis,Least Absolute Shrinkage and Selection Operator(LASSO)regression analysis,and K-nearest neighbors(KNN)analysis were established for predicting the accuracy,determination coefficient(R2)and root mean square error(RMSE),and the regression equation for predicting cartilage thickness was established.Results The knee joint cartilage thicknesses determined by preoperative MRI analysis,robotic navigation system tracing,tissue section of surgical specimen had no statistically significant difference with that by digital vernier caliper(P>0.05).The predictive efficiencies of models of linear regression analysis,principal component analysis,and LASSO regression analysis for the knee joint cartilage thickness all failed to meet the expectations(R2<0.3,RMSE>0.03).The predictive effect of KNN model on the cartilage thickness of the distal femur lateral condyle and lateral tibial plateau was not ideal(R2=0.23,RMSE=0.29),while it had potential predictive value(accuracy=0.21,accuracy=0.15).Conclusion The prediction model of knee joint cartilage thickness based on individual parameters has certain scientificity,and the feasibility of KNN model is relatively high.However,due to insufficient sample size and unclear individual parameter weight,the efficiencies of the four established prediction models are not ideal,which fails to provide definite prediction equations.Therefore,the construction scheme of the prediction model still needs to be further optimized.
9.A prospective study on the impact of surgical treatment on postoperative quality of life and mediating factors in breast cancer patients
Qingxian XU ; Yuan LI ; Maoshan CHEN ; Shi WANG ; Wei RONG ; Lei YANG ; Tingyue HUANG ; Heng YIN ; Jun FAN ; Wei XU ; Qiuling SHI ; Hongwei YANG
Chinese Journal of General Surgery 2025;34(5):978-987
Background and Aims:Surgical treatment is a cornerstone of breast cancer management;however,the physical trauma and psychological burden associated with surgery may adversely affect patients'quality of life(QoL).Based on data from a prospective cohort,this study was conducted to evaluate changes in postoperative QoL among breast cancer patients and to identify mediating factors influencing QoL,thereby providing evidence for perioperative rehabilitation strategies.Methods:Female breast cancer patients who underwent local surgical treatment at Suining Central Hospital between June 2024 and January 2025 were enrolled.The Constant-Murley Shoulder Score,EORTC QLQ-C30,and QLQ-BR23 questionnaires were used pre-and postoperatively to assess shoulder joint function,and QoL.Paired t-tests were used to analyze changes in scores before and after surgery.A mediation model was applied to explore the indirect pathways through which surgery impacts QoL.Additionally,subgroup analyses were conducted to compare QoL changes across different surgical modalities.Results:A total of 148 patients were included,with median age of 54(46-60)years old Postoperative psychological health significantly improved,while shoulder function and overall QoL scores markedly declined(all P<0.001).According to QLQ-C30,functional domains such as physical and role functioning worsened,while symptom burden increased.The QLQ-BR23 revealed significantly higher scores for breast and upper limb symptoms postoperatively(both P<0.001).Subgroup analyses showed that patients undergoing axillary lymph node dissection experienced greater declines in shoulder function and QoL compared to those receiving sentinel lymph node biopsy(both P<0.05).QoL deterioration was comparable between mastectomy and breast-conserving surgery,although the former was associated with more prominent pain and breast symptoms.Mediation analysis indicated that shoulder function,breast symptoms,and physical functioning served as mediators in the impact of surgery on QoL,while better psychological health exerted a protective effect.Conclusion:Surgical treatment significantly affects postoperative QoL in breast cancer patients,with local functional impairment and symptom exacerbation serving as key mediators.Different surgical approaches have varying impacts on QoL.Enhancing postoperative shoulder rehabilitation,symptom management,and psychological support may improve patients'QoL.
10.A multicenter clinical study on intramedullary vancomycin injection for preventing periprosthetic joint infection in total knee arthroplasty
Te LIU ; Jun FU ; Shiguang LAI ; Zhuo ZHANG ; Chi XU ; Lei GENG ; Yang LUO ; Peng REN ; Xin ZHI ; Quanbo JI ; Heng ZHANG ; Runkai ZHAO ; Haichao REN ; Ye TAO ; Qingyuan ZHENG ; Zeyu FENG ; Jianfeng YANG ; Yiming WANG ; Pengcheng LI ; Shuai LIU ; Wei CHAI ; Xiang LI ; Huiwu LI ; Xiaogang ZHANG ; Baochao JI ; Xianzhe LIU ; Xinzhan MAO ; Jianbing MA ; Xiangxiang SUN ; Jiying CHEN ; Yonggang ZHOU ; Jinliang WANG ; Weijun WANG ; Guoqiang ZHANG ; Ming NI
Chinese Journal of Orthopaedics 2025;45(12):803-811
Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

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