1.PANoptosis: a New Target for Cardiovascular Diseases
Xin-Nong CHEN ; Ying-Xi YANG ; Xiao-Chen GUO ; Jun-Ping ZHANG ; Na-Wen LIU
Progress in Biochemistry and Biophysics 2025;52(5):1113-1125
The innate immune system detects cellular stressors and microbial infections, activating programmed cell death (PCD) pathways to eliminate intracellular pathogens and maintain homeostasis. Among these pathways, pyroptosis, apoptosis, and necroptosis represent the most characteristic forms of PCD. Although initially regarded as mechanistically distinct, emerging research has revealed significant crosstalk among their signaling cascades. Consequently, the concept of PANoptosis has been proposed—an inflammatory cell death pathway driven by caspases and receptor-interacting protein kinases (RIPKs), and regulated by the PANoptosome, which integrates key features of pyroptosis, apoptosis, and necroptosis. The core mechanism of PANoptosis involves the assembly and activation of the PANoptosome, a macromolecular complex composed of three structural components: sensor proteins, adaptor proteins, and effector proteins. Sensors detect upstream stimuli and transmit signals downstream, recruiting critical molecules via adaptors to form a molecular scaffold. This scaffold activates effectors, triggering intracellular signaling cascades that culminate in PANoptosis. The PANoptosome is regulated by upstream molecules such as interferon regulatory factor 1 (IRF1), transforming growth factor beta-activated kinase 1 (TAK1), and adenosine deaminase acting on RNA 1 (ADAR1), which function as molecular switches to control PANoptosis. Targeting these switches represents a promising therapeutic strategy. Furthermore, PANoptosis is influenced by organelle functions, including those of the mitochondria, endoplasmic reticulum, and lysosomes, highlighting organelle-targeted interventions as effective regulatory approaches. Cardiovascular diseases (CVDs), the leading global cause of morbidity and mortality, are profoundly impacted by PCD. Extensive crosstalk among multiple cell death pathways in CVDs suggests a complex regulatory network. As a novel cell death modality bridging pyroptosis, apoptosis, and necroptosis, PANoptosis offers fresh insights into the complexity of cell death and provides innovative strategies for CVD treatment. This review summarizes current evidence linking PANoptosis to various CVDs, including myocardial ischemia/reperfusion injury, myocardial infarction, heart failure, arrhythmogenic cardiomyopathy, sepsis-induced cardiomyopathy, cardiotoxic injury, atherosclerosis, abdominal aortic aneurysm, thoracic aortic aneurysm and dissection, and vascular toxic injury, thereby providing critical clinical insights into CVD pathophysiology. However, the current understanding of PANoptosis in CVDs remains incomplete. First, while PANoptosis in cardiomyocytes and vascular smooth muscle cells has been implicated in CVD pathogenesis, its role in other cell types—such as vascular endothelial cells and immune cells (e.g., macrophages)—warrants further investigation. Second, although pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are known to activate the PANoptosome in infectious diseases, the stimuli driving PANoptosis in CVDs remain poorly defined. Additionally, methodological challenges persist in identifying PANoptosome assembly in CVDs and in establishing reliable PANoptosis models. Beyond the diseases discussed, PANoptosis may also play a role in viral myocarditis and diabetic cardiomyopathy, necessitating further exploration. In conclusion, elucidating the role of PANoptosis in CVDs opens new avenues for drug development. Targeting this pathway could yield transformative therapies, addressing unmet clinical needs in cardiovascular medicine.
2.Analysis of risk factors of pleural effusion after spinal separation
Keyi WANG ; Hao QU ; Wen WANG ; Zhaonong YAO ; Xiaowei ZHOU ; Yuhong YAO ; Hengyuan LI ; Peng LIN ; Xiumao LI ; Xiaobo YAN ; Meng LIU ; Xin HUANG ; Nong LIN ; Zhaoming YE
Chinese Journal of Orthopaedics 2024;44(3):169-176
Objective:To investigate the risk factors of pleural effusion after spinal separation surgery for patients with spinal metastatic tumors.Methods:A total of 427 patients with spinal metastatic tumors from January 2014 to January 2022 in the Second Affiliated Hospital of Zhejiang University School of Medicine were retrospectively analyzed. There were 252 males and 175 females, with an average age of 59±12 years (range, 15-87 years). All patients underwent separation surgery. Based on the chest CT within 1 month after surgery, the volume of pleural effusion was measured individually by reconstruction software. Pleural effusion was defined as small volume (0-500 ml), moderate volume (500-1 000 ml), and large volume (above 1 000 ml). Baseline data and perioperative clinical outcomes were compared between the groups, and indicators with statistically significant differences were included in a binary logistic regression analysis to determine the independent risk factors for the development of pleural effusion after isolation of spinal metastatic cancer. Receiver operating characteristic (ROC) curves were conducted to calculate the area under the curve (AUC) for each independent risk factor.Results:All patients successfully completed the operation. Among the 427 patients, there were 35 cases of large pleural effusion, 42 cases of moderate pleural effusion, and 350 cases of small pleural effusion. There were significant differences in tumor size (χ 2=9.485, P=0.013), intraoperative blood loss ( Z=-2.503, P=0.011), blood transfusion ( Z=-2.983, P=0.003), preoperative total protein ( Z=2.681, P=0.007), preoperative albumin ( Z=1.720, P= 0.085), postoperative hemoglobin ( t=2.950, P=0.008), postoperative total protein ( Z=4.192, P<0.001), and postoperative albumin ( t=2.268, P=0.032) in the large pleural effusion group versus the small and moderate pleural effusion group. Logistic regression analysis showed that decreased preoperative albumin ( OR=0.89, P=0.045) and metastases located in the thoracic spine ( OR=4.01, P=0.039) were independent risk factors for the occurrence of large pleural effusion after separation surgery. The ROC curve showed that the AUC and 95% CI for preoperative albumin, lesion location, and the combined model were 0.637 (0.54, 0.74), 0.421 (0.36, 0.48), and 0.883 (0.81, 0.92). The combined predictive model showed good predictive value. Conclusion:The volume of pleural effusion can be measured individually and quantitatively based on chest CT. Decreased preoperative albumin and metastases located in the thoracic spine are independent risk factors for the occurrence of large pleural effusion after separation surgery. The combined prediction of the two factors has better predictive efficacy.
3.Mini-open excision of osteoid osteoma using burrs with the guidance of O-arm navigation
Hengyuan LI ; Xiaobo YAN ; Xin HUANG ; Meng LIU ; Peng LIN ; Hao QU ; Xiumao LI ; Binghao LI ; Shengdong WANG ; Jiadan WU ; Zhaonong YAO ; Keyi WANG ; Nong LIN ; Zhaoming YE
Chinese Journal of Orthopaedics 2023;43(3):164-171
Objective:To investigate the surgical method and clinical effect of O-arm navigation mini-open burring for osteoid osteoma.Methods:Eighteen patients with osteoid osteoma were treated with O-arm guided grinding drill from June 2021 to May 2022, including 15 males and 3 females, the age was (18.4 ±10.9) years (range 2 to 44 years), and the course of disease ranged from 1 week to 3 years (mean 14.2 months). The lesions sites included 6 cases of proximal femur, 3 cases of distal femur, 4 cases of proximal tibia, 1 case of distal tibia, 2 cases of proximal fibula and 1 case of distal and proximal humerus. During the operation, the O-arm navigation was used to determine the location of the focus, the muscle and soft tissue was peeled off to the bone surface through a 1-4 cm small incision, the channel retractor was placed, and the burr was registered as a navigation recognition device to gradually remove the bone on the surface of the tumor nest, and the tumor nest was scraped with a curette for pathological examination; according to the navigation image, the focus was enlarged removed with burr and the grinding range was confirmed by the O-arm X-ray machine before the end of the operation. The patients were followed up for 6 to 15 months (mean 9.5 months). CT scans were performed before and after surgery for imaging comparison in order to figure out whether it had residual lesions or recurrence. The visual analogue score (VAS) of pain was used as a parameter for evaluating the clinical efficacy.Results:The operation time of 18 cases was 40-175 min, with an average of 89.3 min. The time required to establish navigation image was 18.0 ±4.1 min (range 13 ~ 22 min). The length of the incision was 2.7±1.1 cm (range 1-4 cm). All patients achieved complete curettage of the lesions, and osteoid osteoma was confirmed by pathology after operation. All the patients could move to the ground 24 hours after operation, and the pain was significantly relieved from 3 to 7 d after operation, and the pain almost disappeared 3 months after operation. The VAS score of 18 cases was 5.33±1.24 before surgery, 2.79±1.32 on the 3rd day, 1.86±1.21 on the 7th day, 0.86±0.93 on the 1st month, 0.33±0.48 on the 3rd month, and 0.09±0.29 on the 6th month after operation, and the difference was statistically significant ( F=58.50, P<0.001). There were no serious complications during and after operation, and the success rate of treatment (no recurrence of symptoms, no residual recurrence of imaging lesions, no serious complications after operation) was 100%. Conclusion:Treatment of osteoid osteoma with mini-open excision using burrs under the navigation of O-arm is a simple, safe, minimally invasive and efficient technique. Intraoperative precise positioning and the use of burr with navigation to remove a larger area than the tumor nest are the keys to successful treatment.
4.Association between muscle mass and quality of life in Shaanxi adults.
Zi Ping WANG ; Hui JING ; Yu Xin TENG ; Yan HUANG ; Samuel CHACHA ; Ye Zhou LIU ; Bin Yan ZHANG ; Yuan SHEN ; Qiang LI ; Bai Bing MI ; Jiao Mei YANG ; Hong YAN ; Shao Nong DANG
Chinese Journal of Epidemiology 2023;44(6):877-884
Objective: To investigate the association between muscle mass and quality of life in adults in Shaanxi adults. Methods: The data in this analysis were part of the baseline survey of the Regional Ethnic Cohort Study in Northwest China from June 2018 to May 2019 in Shaanxi Province. The participants' quality of life, including physical component summary (PCS) and mental component summary (MCS), was assessed by the 12-Item Short Form Survey, and the Body Fat Determination System measured muscle mass. A logistic regression model with adjustment for confounding factors was established to analyze the association between muscle mass and quality of life in different genders. Further, sensitivity and subgroup analyses were conducted to explore its stability. Finally, a restricted cubic spline was employed to investigate the dose-response relationship between muscle mass and quality of life in different genders. Results: A total of 20 595 participants were included, with an average age of 55.0, and 33.4% were male. After controlling for potential confounders, compared with the Q1 group, the risk of low PCS was reduced by 20.6% (OR=0.794, 95%CI: 0.681-0.925) and the risk of low MCS was lower reduced by 20.1% (OR=0.799, 95%CI: 0.689-0.926) in female Q5 groups. Compared with the Q1 group, the risk of low PCS was reduced by 24.4% (OR=0.756, 95%CI: 0.644-0.888) in the male Q2 group. However, no significant association between muscle mass and MCS in males has been found. In females, restricted cubic spline analysis showed a significant linear dose-response relationship between muscle mass and PCS and MCS. Conclusions: There is a positive association between muscle mass and quality of life in Shaanxi adults, especially females. With the increase in muscle mass, the physical and mental functions of the population continue to improve.
Humans
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Female
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Adult
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Male
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Quality of Life
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Cohort Studies
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Adipose Tissue
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China
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Muscles
5.Expression of LINC01152 in glioma and its effect on malignant biological behavior of glioma cells
Xin Li ; Chang Liu ; Chunhong Xue ; Ping Wang ; Feng Li ; Yingying Ge ; Weixia Nong ; Qingmei Zhang ; Xiaoxun Xie ; Bin Luo
Acta Universitatis Medicinalis Anhui 2023;58(4):622-629
Objective:
To study the expression of long non-coding RNA LINC01152 in glioma and its influence on the malignant biological behavior of glioma cells.
Methods:
LINC01152 expression in glioma was analyzed by LncSpA V2.0 and GEPIA database.qRT-PCR was applied to detect the expression of LINC01152 mRNA in 10 samples of human normal brain tissues,40 samples of glioma tissues and 5 glioma cell lines.GO and KEGG enrichment analysis of LINC01152 co-expressed genes were performed using the DAVID database to predict the related functions. The AnoLnc2,TargetScan,LinkedOmics and miRDB databases were used to predict the LINC01152 related miRNAs and target genes to construct a ceRNA regulatory network.LINC01152 expression was knocked down in glioma cell lines by small interfering RNA (siRNA) transfection.The CCK-8 test,scratch healing experiments,Transwell,flow cytometry and Western blot experiments were used to measure the influence of LINC01152 on the proliferation,migra- tion,invasion and apoptosis of glioma cells.
Results :
Database analysis showed that compared with other tumor types,LINC01152 was highly expressed in glioblastoma (GBM) and low grade glioma (LGG) ,and was higher than normal brain tissue.qRT-PCR showed that the expression of LINC01152 mRNA in glioma tissues was significantly higher than that in normal brain tissues (P<0. 01).The expression of LINC01152 was correlated with Ki-67 (P < 0. 05) ,but not with clinical parameters such as gender,age,tumor size,P53 protein,glial fibrillary acidic protein (GFAP) ,O-6-methylguanine-DNAmethyltransferase ( MGMT) and WHO grade of glioma patients. Functional enrichment analysis of co-expressed genes indicated that the LINC01152 was mainly involved in biological processes such as cell adhesion and synaptic signaling.LINC01152-miRNA-mRNA regulatory network was constructed according to predicted target genes.After down-regulation of LINC01152 expression,the proliferation,migration and invasion abilities of A172 and U87 cells decreased(P<0. 01) ,while the apoptosis of glioma cells significantly increased (P<0. 001) .
Conclusion
LINC01152 is highly expressed in glioma,which can promote the malignant biological behavior of glioma cells by enhancing proliferation,migration as well as invasion and inhibition of apoptosis.
6.Study on knowledge, attitudes and practices of pulse oximetry among pediatric healthcare providers in China and their influencing factors
Fengxia XUE ; Yuejie ZHENG ; Adong SHEN ; Hanmin LIU ; Xing CHEN ; Lili ZHONG ; Guangmin NONG ; Xin SUN ; Gen LU ; Shenggang DING ; Yuanxun FANG ; Jiahua PAN ; Zhiying HAN ; Yun SUN ; Qiang CHEN ; Yi JIANG ; Xiaoping ZHU ; Suping TANG ; Xiufang WANG ; Changshan LIU ; Shaomin REN ; Zhimin CHEN ; Deyu ZHAO ; Yong YIN ; Rongfang ZHANG ; Ming LI ; Yunxiao SHANG ; Yaping MU ; Shuhua AN ; Yangzom YESHE ; Peiru XU ; Yan XING ; Baoping XU ; Jing ZHAO ; Shi CHEN ; Wei XIANG ; Lihong LI ; Enmei LIU ; Yuxin SONG ; Yonghong YANG ; Kunling SHEN
Chinese Journal of Applied Clinical Pediatrics 2022;37(23):1807-1812
Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.
7.Preventive strategy of economy class syndrome.
Xin Nong LIU ; Tong ZHANG ; Yu Long JIA
Chinese Journal of Preventive Medicine 2022;56(8):1150-1153
Economy class syndrome (ECS) refers to a series of symptoms, such as lower limb swelling, chest pain, dyspnea, and sudden death, that occur during or after a long-distance flight. Its essence is venous thromboembolism. ECS, as a preventable syndrome, is one of the causes of sudden death in long-distance travelers. Medical assistance to the African region is a very important diplomatic matter of China. It often takes medical workers more than 10 hours of long-distance flight to reach the recipient country. Therefore, it is essential to improve the understanding of ECS and corresponding prevention strategies among the long-distance traveling people including medical workers assisting Africa, which could guarantee their health and ensure the smooth implementation of the work of assisting Africa.
Africa
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China
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Death, Sudden
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Humans
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Syndrome
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Travel
8.Analysis of the new WHO guideline to accelerate the progress towards elimination of schistosomiasis in China.
Zhao Yu GUO ; Jia Xin FENG ; Li Juan ZHANG ; Yi Biao ZHOU ; Jie ZHOU ; Kun YANG ; Yang LIU ; Dan Dan LIN ; Jian Bing LIU ; Yi DONG ; Tian Ping WANG ; Li Yong WEN ; Min Jun JI ; Zhong Dao WU ; Qing Wu JIANG ; Song LIANG ; Jia Gang GUO ; Chun Li CAO ; Jing XU ; Shan LÜ ; Shi Zhu LI ; Xiao Nong ZHOU
Chinese Journal of Schistosomiasis Control 2022;34(3):217-222
On February 2022, WHO released the evidence-based guideline on control and elimination of human schistosomiasis, with aims to guide the elimination of schistosomiasis as a public health problem in disease-endemic countries by 2030 and promote the interruption of schistosomiasis transmission across the world. Based on the One Health concept, six evidence-based recommendations were proposed in this guideline. This article aims to analyze the feasibility of key aspects of this guideline in Chinese national schistosomiasis control program and illustrate the significance to guide the future actions for Chinese national schistosomiasis control program. Currently, the One Health concept has been embodied in the Chinese national schistosomiasis control program. Based on this new WHO guideline, the following recommendations are proposed for the national schistosomiasis control program of China: (1) improving the systematic framework building, facilitating the agreement of the cross-sectoral consensus, and building a high-level leadership group; (2) optimizing the current human and livestock treatments in the national schistosomiasis control program of China; (3) developing highly sensitive and specific diagnostics and the framework for verifying elimination of schistosomiasis; (4) accelerating the progress towards elimination of schistosomiasis and other parasitic diseases through integrating the national control programs for other parasitic diseases.
China/epidemiology*
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Disease Eradication
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Humans
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Public Health
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Schistosomiasis/prevention & control*
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World Health Organization
9.The immune microenvironment of giant cell tumor of bone and its role as an indicator to denosumab administration
Binghao LI ; Xiaobo YAN ; Meng LIU ; Weibo PAN ; Xin HUANG ; Nong LIN ; Zhaoming YE
Chinese Journal of Orthopaedics 2021;41(16):1081-1089
Objective:To investigate the alteration of immune microenvironment in giant cell tumor of bone (GCTB) after denosumab treatment from the aspect of immune cellsat single-cell level.Methods:During Nov 2018 and May 2020, fresh tumor excision tissues from GCTB cases were collected and received CyTOF analyses. CyTOF datasets were analyzed and visualized by t-distributed stochastic neighbor embedding (TSNE) method of reduction dimension. The compositions of immune cells in GCTB with or without denosumab treatment were compared. The supernatant of culture medium of ex vivo inoculated primary tumor tissues was harvested to clarify if the culturing supernatant could affect cell growth.Results:A total of 15 primary GCTB cases and three denosumab-treated samples were included in this study and were sent for CyTOF and multicolor FACS assay. GCTB was featured of T-cell and macrophage-like myeloid cell-dominant immune microenvironment. After denosumab treatment, the percentage of T-cells was significantly elevated, while the number of macrophage-like myeloid cells were reduced. Furthermore, the ratio of macrophage-like myeloid cells in total live cells was associated with the treatment period of denosumab. The multinuclear osteoclast like giant cells were characterized by the expression of γδTCR, while most of the intratumoral CD8+ T-cells were activated PD-1+CD69+T-cells. The culturing supernatant of denosumab treatment-free GCTB tissues reinforced cell proliferation in vitro, while this phenomenon was not seen when using denosumab treated tissues.Conclusion:Illustrated the immune cell atlas of GCTB, and preliminarily investigated the potential effects of immune cells on tumor progression in GCTB, providing some theoretical clues for prolonged use of denosumab in unresectable GCTB cases.
10.3D printed hemipelvic prosthesis for treatment of pelvic malignant tumors resected via sacroiliac joint
Xin HUANG ; Hao QU ; Nong LIN ; Weibo PAN ; Xiaobo YAN ; Meng LIU ; Peng LIN ; Hengyuan LI ; Zhaoming YE
Chinese Journal of Orthopaedics 2021;41(16):1116-1124
Objective:To analyze the surgical techniques, surgical indications and early clinical effects of 3D printed hemipelvic prostheses in the reconstruction of pelvic malignant tumors resected by the sacroiliac joint.Methods:From January 2016 to March 2020, a retrospective analysis of 9 patients with malignant tumors involving pelvis I+II or I+II+III region were treated with sacroiliac joint osteotomy and 3D printed pelvic prosthesis reconstruction. There were 7 males and 2 females; their age was 51.1±10.5 years (range 27-66 years). Among them, 5 cases were chondrosarcoma, 1 case was pleomorphic undifferentiated sarcoma, 2 cases were metastatic renal cell carcinoma, and 1 case was metastatic primitive neuroectodermal tumor. Resection of pelvic area I+II or I+II+III were according to the extent of tumor involvement. During the resection of pelvic I region, osteotomy was done through sacroiliac joint surface, and 3D printed hemipelvic prosthesis that fits the sacral auricular surface was used for reconstruction. Postoperative imaging examination was used to evaluate the acetabular rotation center deviation of the pelvic prosthesis; the International Bone Tumor Society (Musculoskeletal Tumor Society, MSTS) function score was used for functional evaluation; the patient's oncology outcome and postoperative complications were evaluated.Results:All 9 patients successfully completed the operation. The operation time was 3.5-6 hours, with an average of 4.5 hours. The intraoperative blood loss was 800-3 000 ml, with an average of 1 400 ml. 3 patients underwent resection and reconstruction of pelvis I+II area, 4 patients underwent pelvic resection and reconstruction of I+II+III area, 2 patients underwent pelvic I+II+III area combined with proximal femur resection and reconstruction; all patients were followed up. The follow-up time was 6-50 months, with an average of 16 months. At the last follow-up of 9 patients, the MSTS score was 12-26, with an average of 20.2; the postoperative rotation center horizontal displacement distance was 10.67±7.12 mm, and the vertical displacement was 8.56±4.22 mm. One case of metastatic cancer was found to have multiple metastases throughout the body during chemotherapy 3 months after surgery, and died in 7 months after surgery; 1 case of pelvic metastatic renal cell carcinoma developed multiple metastases within one and a half years after surgery, controlled by targeted drugs, and survived with the tumor; the rest seven cases had no recurrence at the surgical site and no distant metastasis was found.Conclusion:The semipelvic prosthesis with 3D printed auricular surface has potential advantages in reconstructing the bone defect of the pelvis I+II or I+II+III area after the sacroiliac joint osteotomy. The short-term efficacy is relatively satisfactory, and the long-term efficacy remains to be further observed.


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