1.Digital technology-assisted debridement and bone and soft tissue reconstruction for the treatment of chronic osteomyelitis of the tibia
Hongying HE ; Weidong SHI ; Wenxing HAN ; Li HAN ; Huhu WANG ; Jianwen ZHAO ; Zhuo WU ; Shaoguang LI ; Rongji ZHANG ; Yanhui GUO ; Jianzheng ZHANG
Chinese Journal of Orthopaedics 2025;45(8):500-507
Objective:To evaluate the safety and efficacy of digital technology-assisted debridement and bone and soft tissue reconstruction in the treatment of chronic osteomyelitis of the tibia.Methods:This retrospective study analyzed clinical data from 38 patients (26 males, 12 females; mean age 45.61±18.36 years, range 16-83 years) with chronic post-traumatic osteomyelitis complicated by soft tissue defects in the tibia, treated at the Department of Orthopaedics, Fourth Medical Center of PLA General Hospital between June 2021 and June 2023. There were 18 cases of traffic accidents, 6 cases of high-altitude falls, 6 cases of heavy objects and 6 cases of low-energy falls. Lesion sites: 12 cases in the upper segment of the tibia, 12 cases in the middle segment, and 14 cases in the lower segment. According to the Cierny-Mader classification, there were 24 cases of type III and 14 cases of type IV. Before the operation, the "3D point cloud technology" was used to plan the debridement range of bone and soft tissue. During the operation, the optical navigation system was used to monitor the debridement range in real time. The flap was designed by combining "Reading Tablet Treasure" with CT angiography, and the amount of bone graft was predicted by AI algorithm. The surgical method adopted is the Masquelet technique, namely thorough debridement, bone cement occupation and soft tissue repair in the first stage, and bone reconstruction in the second stage. Comparing the calculated bone defect amount and soft tissue defect area before the operation with the actual measured values after debridement. The cure rate of infection was evaluated by using the McKee bone infection treatment criteria after the operation. The visual analogue scale (VAS) for pain, lower extremity functional scale (LEFS), and self-rating anxiety scale (SAS) were used to evaluate the improvement of the quality of life of postoperative patients.Results:38 patients were followed up with a mean follow-up of 13.53±2.37 months. 37 patients' infections were effectively controlled, and 1 patient had a recurrence of infection, with an effectiveness rate of 97% for the treatment of McKee's infections. The preoperative calculated bone defect amount and soft tissue defect area were 51.05±26.31 cm 3 and 68.42±43.45 cm 2 respectively, and the actual measured values after debridement during the operation were 51.66±26.35 cm 3 and 68.82±43.76 cm 2 respectively. There was no statistically significant difference before and after the operation ( P>0.05). The interval between the first and second stage surgeries was 10.36±1.61 weeks, and all flaps survived after the first stage surgery. Two months after the operation, one case had recurrent osteomyelitis. After palliative treatment, sinus tracts were formed at the infection site. At the 12-month regular dressing change follow-up, there were still purulent secretions in the sinus tracts. There was no recurrence of infection after primary debridement in 37 cases, and the bone grafts healed. The bone healing time was 3.58±0.97 months. The postoperative VAS, LEFS, and SAS scores were 1.00±0.91, 66.68±7.91, and 34.30±4.29, respectively, which were significantly improved compared with the preoperative scores of 7.54±1.52, 21.22±4.29, and 52.70±6.74, respectively, and the difference was statistically significant ( P<0.05). Conclusions:The application of digital technology to precisely design the debridement range of bone and soft tissue, and the real-time holographic visualization monitoring of the debridement range during the operation can achieve precise debridement of bone and soft tissue and personalized and precise repair of soft tissue defects. It is a safe and effective technique for the treatment of chronic osteomyelitis of the tibia.
2.A comparative study of allogeneic versus autologous platelet rich plasma gels in repair of bone defects
Min LYU ; Da GUO ; Kesong ZHANG ; Long BI ; Junjun FAN ; Dan LI ; Wenxing YU ; Hu LIANG
Chinese Journal of Orthopaedic Trauma 2025;27(11):994-1001
Objective:To compare the differences in repair of rabbit bone defects between allogeneic platelet rich plasma (PRP) gel and autologous PRP gel.Methods:Thirty-six healthy New Zealand white rabbits were selected and randomly divided into an autologous group, an allogeneic group, and a control group ( n=12). A model of bilateral forelimb bone defects was established in each group. The autologous group was repaired with self-made deproteinized bone scaffold materials + autologous bone marrow mesenchymal stem cells (BMSCs) + autologous PRP gel, the allogeneic group with self-made deproteinized bone scaffold materials + autologous BMSCs + allogeneic PRP gel, and the control group with only self-made deproteinized bone scaffold materials + autologous BMSCs. At postoperative 1, 2, and 3 months, 4 animals were euthanized in each group, respectively, for gross observation, X-ray examination, Micro-CT examination, biomechanical testing and histological analysis (HE staining for tissue morphology) to compare the differences in repair of bone defects. Results:The formation of trabecular bone, cortical reconstruction, and medullary recanalization occurred earlier in the autologous and allogeneic groups than in the control group. Micro-CT analysis at postoperative 2 months showed that bone mineral density [(281.51±33.69) mg/mL and (266.13±37.13) mg/mL], bone volume fraction (23.52%±2.81% and 21.91%±1.94%), and trabecular number [(1.68±0.29) mm -1 and (1.63±0.22) mm -1] in the autologous and allogeneic groups were significantly higher than those in the control group [(197.47±18.61) mg/mL, 16.54%±3.06%, and (1.06±0.11) mm -1] ( P<0.05). No significant differences were found among the 3 groups in trabecular thickness [(0.33±0.09) mm, (0.42±0.16) mm, and (0.28±0.13) mm] or in the maximum compressive load ( P>0.05). HE staining revealed a significantly greater number and earlier formation of chondrocytes and osteoblasts in the autologous and allogeneic groups than in the control group. Conclusion:Since allogeneic PRP exhibits similar efficacy in promoting new bone formation compared with autologous PRP in a rabbit bone defect model, it may serve as a viable substitute for autologous PRP.
3.Digital technology-assisted debridement and bone and soft tissue reconstruction for the treatment of chronic osteomyelitis of the tibia
Hongying HE ; Weidong SHI ; Wenxing HAN ; Li HAN ; Huhu WANG ; Jianwen ZHAO ; Zhuo WU ; Shaoguang LI ; Rongji ZHANG ; Yanhui GUO ; Jianzheng ZHANG
Chinese Journal of Orthopaedics 2025;45(8):500-507
Objective:To evaluate the safety and efficacy of digital technology-assisted debridement and bone and soft tissue reconstruction in the treatment of chronic osteomyelitis of the tibia.Methods:This retrospective study analyzed clinical data from 38 patients (26 males, 12 females; mean age 45.61±18.36 years, range 16-83 years) with chronic post-traumatic osteomyelitis complicated by soft tissue defects in the tibia, treated at the Department of Orthopaedics, Fourth Medical Center of PLA General Hospital between June 2021 and June 2023. There were 18 cases of traffic accidents, 6 cases of high-altitude falls, 6 cases of heavy objects and 6 cases of low-energy falls. Lesion sites: 12 cases in the upper segment of the tibia, 12 cases in the middle segment, and 14 cases in the lower segment. According to the Cierny-Mader classification, there were 24 cases of type III and 14 cases of type IV. Before the operation, the "3D point cloud technology" was used to plan the debridement range of bone and soft tissue. During the operation, the optical navigation system was used to monitor the debridement range in real time. The flap was designed by combining "Reading Tablet Treasure" with CT angiography, and the amount of bone graft was predicted by AI algorithm. The surgical method adopted is the Masquelet technique, namely thorough debridement, bone cement occupation and soft tissue repair in the first stage, and bone reconstruction in the second stage. Comparing the calculated bone defect amount and soft tissue defect area before the operation with the actual measured values after debridement. The cure rate of infection was evaluated by using the McKee bone infection treatment criteria after the operation. The visual analogue scale (VAS) for pain, lower extremity functional scale (LEFS), and self-rating anxiety scale (SAS) were used to evaluate the improvement of the quality of life of postoperative patients.Results:38 patients were followed up with a mean follow-up of 13.53±2.37 months. 37 patients' infections were effectively controlled, and 1 patient had a recurrence of infection, with an effectiveness rate of 97% for the treatment of McKee's infections. The preoperative calculated bone defect amount and soft tissue defect area were 51.05±26.31 cm 3 and 68.42±43.45 cm 2 respectively, and the actual measured values after debridement during the operation were 51.66±26.35 cm 3 and 68.82±43.76 cm 2 respectively. There was no statistically significant difference before and after the operation ( P>0.05). The interval between the first and second stage surgeries was 10.36±1.61 weeks, and all flaps survived after the first stage surgery. Two months after the operation, one case had recurrent osteomyelitis. After palliative treatment, sinus tracts were formed at the infection site. At the 12-month regular dressing change follow-up, there were still purulent secretions in the sinus tracts. There was no recurrence of infection after primary debridement in 37 cases, and the bone grafts healed. The bone healing time was 3.58±0.97 months. The postoperative VAS, LEFS, and SAS scores were 1.00±0.91, 66.68±7.91, and 34.30±4.29, respectively, which were significantly improved compared with the preoperative scores of 7.54±1.52, 21.22±4.29, and 52.70±6.74, respectively, and the difference was statistically significant ( P<0.05). Conclusions:The application of digital technology to precisely design the debridement range of bone and soft tissue, and the real-time holographic visualization monitoring of the debridement range during the operation can achieve precise debridement of bone and soft tissue and personalized and precise repair of soft tissue defects. It is a safe and effective technique for the treatment of chronic osteomyelitis of the tibia.
4.Application of the surgical system in robot-assisted laparoscopic partial splenectomy for benign splenic lesions
Jia GUO ; Ji WANG ; Hongqin MA ; Li LIU ; Yusheng DU ; Wenxing ZHAO
Chinese Journal of Hepatobiliary Surgery 2025;31(8):616-620
Objective:To evaluate the efficacy and safety of da Vinci robot-assisted laparoscopic partial splenectomy (LPS).Methods:A retrospective review was conducted on 12 patients who underwent robot-assisted LPS for benign splenic lesions at the Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, between January 2021 and August 2024. Among the patients, 5 were males and 7 were females, aged 35(21, 58) years. The operation time, intraoperative blood loss, and other related indicators, as well as postoperative complications and follow-up conditions were reviewed.Results:Robot-assisted LPS was successfully performed in all patients, with no conversions to open surgery, achieving a 100% spleen preservation rate (12/12). The operative time was (168.92±44.64) min, and the intraoperative blood loss was 75 (50, 175) ml, with no intraoperative blood transfusions required. The duration of postoperative drainage tube placement was (3.92±1.44) d, and the postoperative hospital stay was (5.33±1.07) d. No complications, such as bleeding, surgical site effusion, or pancreatic fistula occurred in the 12 patients. Minimal pleural effusion was observed in four cases, which required no special treatment. All patients were followed up for at least 6 months. During the follow-up period, there were no occurrences of portal vein thrombosis, overwhelming post-splenectomy infection, recurrent thrombocytosis, or disease recurrence.Conclusion:Robot-assisted LPS is a safe and feasible surgical approach for benign splenic lesions, demonstrating favorable outcomes.
5.A comparative study of allogeneic versus autologous platelet rich plasma gels in repair of bone defects
Min LYU ; Da GUO ; Kesong ZHANG ; Long BI ; Junjun FAN ; Dan LI ; Wenxing YU ; Hu LIANG
Chinese Journal of Orthopaedic Trauma 2025;27(11):994-1001
Objective:To compare the differences in repair of rabbit bone defects between allogeneic platelet rich plasma (PRP) gel and autologous PRP gel.Methods:Thirty-six healthy New Zealand white rabbits were selected and randomly divided into an autologous group, an allogeneic group, and a control group ( n=12). A model of bilateral forelimb bone defects was established in each group. The autologous group was repaired with self-made deproteinized bone scaffold materials + autologous bone marrow mesenchymal stem cells (BMSCs) + autologous PRP gel, the allogeneic group with self-made deproteinized bone scaffold materials + autologous BMSCs + allogeneic PRP gel, and the control group with only self-made deproteinized bone scaffold materials + autologous BMSCs. At postoperative 1, 2, and 3 months, 4 animals were euthanized in each group, respectively, for gross observation, X-ray examination, Micro-CT examination, biomechanical testing and histological analysis (HE staining for tissue morphology) to compare the differences in repair of bone defects. Results:The formation of trabecular bone, cortical reconstruction, and medullary recanalization occurred earlier in the autologous and allogeneic groups than in the control group. Micro-CT analysis at postoperative 2 months showed that bone mineral density [(281.51±33.69) mg/mL and (266.13±37.13) mg/mL], bone volume fraction (23.52%±2.81% and 21.91%±1.94%), and trabecular number [(1.68±0.29) mm -1 and (1.63±0.22) mm -1] in the autologous and allogeneic groups were significantly higher than those in the control group [(197.47±18.61) mg/mL, 16.54%±3.06%, and (1.06±0.11) mm -1] ( P<0.05). No significant differences were found among the 3 groups in trabecular thickness [(0.33±0.09) mm, (0.42±0.16) mm, and (0.28±0.13) mm] or in the maximum compressive load ( P>0.05). HE staining revealed a significantly greater number and earlier formation of chondrocytes and osteoblasts in the autologous and allogeneic groups than in the control group. Conclusion:Since allogeneic PRP exhibits similar efficacy in promoting new bone formation compared with autologous PRP in a rabbit bone defect model, it may serve as a viable substitute for autologous PRP.
6.Application of the surgical system in robot-assisted laparoscopic partial splenectomy for benign splenic lesions
Jia GUO ; Ji WANG ; Hongqin MA ; Li LIU ; Yusheng DU ; Wenxing ZHAO
Chinese Journal of Hepatobiliary Surgery 2025;31(8):616-620
Objective:To evaluate the efficacy and safety of da Vinci robot-assisted laparoscopic partial splenectomy (LPS).Methods:A retrospective review was conducted on 12 patients who underwent robot-assisted LPS for benign splenic lesions at the Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, between January 2021 and August 2024. Among the patients, 5 were males and 7 were females, aged 35(21, 58) years. The operation time, intraoperative blood loss, and other related indicators, as well as postoperative complications and follow-up conditions were reviewed.Results:Robot-assisted LPS was successfully performed in all patients, with no conversions to open surgery, achieving a 100% spleen preservation rate (12/12). The operative time was (168.92±44.64) min, and the intraoperative blood loss was 75 (50, 175) ml, with no intraoperative blood transfusions required. The duration of postoperative drainage tube placement was (3.92±1.44) d, and the postoperative hospital stay was (5.33±1.07) d. No complications, such as bleeding, surgical site effusion, or pancreatic fistula occurred in the 12 patients. Minimal pleural effusion was observed in four cases, which required no special treatment. All patients were followed up for at least 6 months. During the follow-up period, there were no occurrences of portal vein thrombosis, overwhelming post-splenectomy infection, recurrent thrombocytosis, or disease recurrence.Conclusion:Robot-assisted LPS is a safe and feasible surgical approach for benign splenic lesions, demonstrating favorable outcomes.
7.Clinical value of open abdomen therapy in non-traumatic critically patients: a multicenter retrospective study
Xiaoyu YAN ; Bingkui REN ; Weipeng HUANG ; Feng GUO ; Wenxing TONG ; Xiangde ZHENG ; Lin XUE ; Shuangling LI ; Yongyi CHEN ; Xiangyang LIU ; Jun DUAN ; Lu XU ; Zhigang CHANG
Chinese Journal of Digestive Surgery 2024;23(11):1416-1422
Objective:To investigate the clinical value of open abdomen therapy in non-traumatic critically patients.Methods:The retrospective cohort study was conducted. The clinical data of 23 non-traumatic critically patients who underwent open abdomen therapy in 5 hospitals in China from July 2015 to July 2024 were collected. There were 17 males and 6 females, aged 70(range, 24-84)years. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Repeated measurement data were analyzed using the repeated ANOVA, and pairwise comparison within groups was conducted using the least significant difference method. The Boruta algorithm was applied for analyzing variables related to survival outcomes. Results:(1) Treatment of patients undergoing open abdomen therapy. ① The intra-abdominal pressure, lactate, heart rate, central venous pressure, mean arterial pressure, sequential organ failure assessment score of 23 patients from preoperation to postoperative day 3 were changed from (19.7±5.4)mmHg (1 mmHg=0.133 kPa), (6.1±1.9)mmol/L, (120±14)beats/minutes, (13.1±4.3)cmH 2O (1 cmH 2O=0.098 kPa), (58.8±6.8)mmHg, 13.2±1.8 to (10.6±1.3)mmHg, (2.3±0.6)mmol/L, (95±10)beats/minutes, (8.8±2.0)cmH 2O, (75.2±8.5)mmHg, 10.1±1.6, respectively, showing significant differences in the time effect of changes in the above indicators ( Ftime=46.40, 29.19, 24.91, 11.84, 27.81, 11.71, P<0.05). ② The oxygenation index, total intake, total output of 23 patients from preoperation to postoperative day 3 were changed from (255.0±54.2)mmHg, (5388±1562)mL, (2 520±630)mL to (291.7±25.0)mmHg, (2 886±866)mL, (3 221±923)mL, respectively, showing significant differences in the time effect of changes in the above indicators ( Ftime=7.61, 13.83, 2.97, P<0.05). ③The daily caloric intake, daily protein supplementation of 23 patients from preoperation to postoperative day 3 were changed from (465±116)kcal, (18±5)g to (1 628±472)kcal, (60±18)g, respectively, showing significant differences in the time effect of changes in the above indicators ( Ftime=40.31, 41.23, P<0.05). (2) Patients outcomes after open abdomen therapy. Of 23 patients, 18 cases survived and 5 cases died. The duration of intensive care unit stay and duration of hospital stay of 23 patients were 26(range, 5-82)days and 40(range, 5-98)days. Twelve of 23 patients received renal replacement therapy for 12 (range, 5-32)days. Time of pain and sedation management, mechanical ventilation, antimicrobial therapy, vasopressor therapy of 23 patients were 13(range, 5-74)days, 12(range, 5-74)days,20(range, 5-50)days, 6(range, 2-35)days. (3) Analysis of variables related to survival outcomes for patients after open abdomen therapy. Results of Boruta analysis showed that postoperative high-output enteric fistula, postoperative bile fistula, postoperative intra-abdominal hemorrhage, postoperative enteric air fistula, and preoperative mean arterial pressure were significantly associated with survival outcomes. Conclusions:Open abdomen therapy is effective in the treatment of non-traumatic critically patients. Postoperative high-output enteric fistula, postoperative bile fistula, postoperative intra-abdominal hemorrhage, postoperative enteric air fistula, and preoperative mean arterial pressure reduction are significantly associated with survival outcomes.
8.Clinical value of open abdomen therapy in non-traumatic critically patients: a multicenter retrospective study
Xiaoyu YAN ; Bingkui REN ; Weipeng HUANG ; Feng GUO ; Wenxing TONG ; Xiangde ZHENG ; Lin XUE ; Shuangling LI ; Yongyi CHEN ; Xiangyang LIU ; Jun DUAN ; Lu XU ; Zhigang CHANG
Chinese Journal of Digestive Surgery 2024;23(11):1416-1422
Objective:To investigate the clinical value of open abdomen therapy in non-traumatic critically patients.Methods:The retrospective cohort study was conducted. The clinical data of 23 non-traumatic critically patients who underwent open abdomen therapy in 5 hospitals in China from July 2015 to July 2024 were collected. There were 17 males and 6 females, aged 70(range, 24-84)years. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Repeated measurement data were analyzed using the repeated ANOVA, and pairwise comparison within groups was conducted using the least significant difference method. The Boruta algorithm was applied for analyzing variables related to survival outcomes. Results:(1) Treatment of patients undergoing open abdomen therapy. ① The intra-abdominal pressure, lactate, heart rate, central venous pressure, mean arterial pressure, sequential organ failure assessment score of 23 patients from preoperation to postoperative day 3 were changed from (19.7±5.4)mmHg (1 mmHg=0.133 kPa), (6.1±1.9)mmol/L, (120±14)beats/minutes, (13.1±4.3)cmH 2O (1 cmH 2O=0.098 kPa), (58.8±6.8)mmHg, 13.2±1.8 to (10.6±1.3)mmHg, (2.3±0.6)mmol/L, (95±10)beats/minutes, (8.8±2.0)cmH 2O, (75.2±8.5)mmHg, 10.1±1.6, respectively, showing significant differences in the time effect of changes in the above indicators ( Ftime=46.40, 29.19, 24.91, 11.84, 27.81, 11.71, P<0.05). ② The oxygenation index, total intake, total output of 23 patients from preoperation to postoperative day 3 were changed from (255.0±54.2)mmHg, (5388±1562)mL, (2 520±630)mL to (291.7±25.0)mmHg, (2 886±866)mL, (3 221±923)mL, respectively, showing significant differences in the time effect of changes in the above indicators ( Ftime=7.61, 13.83, 2.97, P<0.05). ③The daily caloric intake, daily protein supplementation of 23 patients from preoperation to postoperative day 3 were changed from (465±116)kcal, (18±5)g to (1 628±472)kcal, (60±18)g, respectively, showing significant differences in the time effect of changes in the above indicators ( Ftime=40.31, 41.23, P<0.05). (2) Patients outcomes after open abdomen therapy. Of 23 patients, 18 cases survived and 5 cases died. The duration of intensive care unit stay and duration of hospital stay of 23 patients were 26(range, 5-82)days and 40(range, 5-98)days. Twelve of 23 patients received renal replacement therapy for 12 (range, 5-32)days. Time of pain and sedation management, mechanical ventilation, antimicrobial therapy, vasopressor therapy of 23 patients were 13(range, 5-74)days, 12(range, 5-74)days,20(range, 5-50)days, 6(range, 2-35)days. (3) Analysis of variables related to survival outcomes for patients after open abdomen therapy. Results of Boruta analysis showed that postoperative high-output enteric fistula, postoperative bile fistula, postoperative intra-abdominal hemorrhage, postoperative enteric air fistula, and preoperative mean arterial pressure were significantly associated with survival outcomes. Conclusions:Open abdomen therapy is effective in the treatment of non-traumatic critically patients. Postoperative high-output enteric fistula, postoperative bile fistula, postoperative intra-abdominal hemorrhage, postoperative enteric air fistula, and preoperative mean arterial pressure reduction are significantly associated with survival outcomes.
9.Anti-convulsant Activity of Goat Horn and Its Effect on Neurotransmitters in Mouse Brain
Zhaoying ZHU ; Wenxing WU ; Jingjing ZHAO ; Rui LIU ; Sheng GUO ; Jin'ao DUAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(3):133-142
ObjectiveTo investigate the anti-convulsant activity of goat horn and its effect on the main neurotransmitters in the brain of model mice. MethodA total of 120 mice were randomly divided into a blank group,a model group,a positive drug group (estazolam, 1 mg·kg-1), a Saigae Tataricae Cornu (STC, 0.2 g·kg-1) group, and low- (1.25 g·kg-1) and high-dose (2.5 g·kg-1) goat horn groups. Drugs were administered by gavage once at 10 mL·kg-1. Those in the blank group and the model group were given the same volume of 0.2% sodium carboxymethyl cellulose (CMC-Na). The mice underwent threshold electrical stimulation once 2 h after administration. Ankylosing convulsion in the hind limbs of mice was used as the index to calculate the recovery period, convulsion rate, and mortality of ankylosing convulsion. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established to analyze the changes in the content of the main neurotransmitters in the brain tissues of mice. ResultTwo hours after intragastric administration of goat horn powder to mice, the recovery period of convulsion could be shortened and the convulsion rate and mortality were reduced (P<0.05). In terms of anti-convulsant effect, the groups were ranked as follows: high-dose goat horn group > STC group > low-dose goat horn group. UPLC-MS/MS analysis showed that compared with the results in the model group, goat horn powder and STC decreased the content of glutamic acid and aspartic acid (P<0.05) and increased the content of glycine, γ-aminobutyric acid, and 5-hydroxytryptamine (P<0.05). ConclusionThe results showed that goat horn had a significant anti-convulsant effect on the electroshock-induced convulsion mouse model, and the underlying mechanism was presumably attributed to the improvement of the development of convulsion by regulating the changes in neurotransmitter content in brain tissues.
10. Acrolein Induces Systemic Coagulopathy via Autophagy-dependent Secretion of von Willebrand Factor in Mice after Traumatic Brain Injury
Wenxing CUI ; Xun WU ; Dayun FENG ; Jianing LUO ; Yingwu SHI ; Wei GUO ; Haixiao LIU ; Qiang WANG ; Liang WANG ; Shunnan GE ; Yan QU
Neuroscience Bulletin 2021;37(8):1160-1175
Traumatic brain injury (TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes, but the pathogenesis remains poorly understood. In this study, we aimed to investigate the causal role of acrolein, a typical lipid peroxidation product, in TBI-induced coagulopathy, and further explore the underlying molecular mechanisms. We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy. Using a controlled cortical impact mouse model, we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor (VWF). Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion. mRNA sequencing (mRNA-seq) and transcriptome analysis indicated that acrolein over-activated autophagy, and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway. In addition, we demonstrated that acrolein was produced in the perilesional cortex, affected endothelial cell integrity, and disrupted the blood-brain barrier. In conclusion, in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage, providing an alternative therapeutic target.

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