1.Thyroid Hormone Network Regulation in MASLD: Mechanisms and Targeted Therapies
Wen-Ping XIAO ; Yang MA ; Heng GUAN ; Sha WAN ; Wen HAN ; Bing-Bing LUO ; Wu-Feng WANG ; Fang LIU
Progress in Biochemistry and Biophysics 2026;53(3):643-661
Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide, affecting approximately 32%-38% of the adult population and posing a growing public health burden. MASLD represents a continuous disease spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), progressive hepatic fibrosis, cirrhosis, and ultimately hepatocellular carcinoma (HCC). The pathological core of MASLD lies in disruption of hepatic lipid metabolic homeostasis, characterized by an imbalance among de novo lipogenesis, fatty acid β-oxidation, and very-low-density lipoprotein (VLDL)-mediated lipid export. This metabolic disequilibrium subsequently drives inflammatory injury and fibrotic progression. Among the multiple regulatory pathways involved, thyroid hormone (TH) signaling has emerged as a central regulator of hepatic metabolic homeostasis. The liver is a major peripheral target organ of TH action, where TH predominantly exerts its metabolic effects through thyroid hormone receptor β (TRβ). Large-scale epidemiological studies and meta-analyses have demonstrated that hypothyroidism is significantly associated with increased MASLD prevalence, more severe histological injury, and advanced hepatic fibrosis, suggesting that dysregulation of TH signaling may participate throughout the entire MASLD disease spectrum. At the molecular level, TH regulates hepatic lipid metabolism by coordinating suppression of lipogenesis, enhancement of mitochondrial fatty acid oxidation, and promotion of VLDL assembly and secretion through integrated genomic actions of the T3-TRβ axis and non-genomic signaling pathways. Across different stages of MASLD, TH signaling exerts stage-dependent protective effects. In the steatosis stage, TH improves metabolic flexibility by modulating insulin sensitivity, glucose metabolism, and lipid droplet clearance, thereby alleviating early lipotoxic stress. During progression to MASH, TH attenuates inflammatory amplification by improving mitochondrial homeostasis, suppressing activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and modulating the gut-liver axis microenvironment. In advanced stages, TH signaling influences hepatic stellate cell activation and extracellular matrix deposition, partly through interaction with the transforming growth factor-β (TGF-β)/SMAD pathway, while alterations in intrahepatic TH availability, mediated by dynamic changes in iodothyronine deiodinase 1 (DIO1), contribute to fibrosis progression and hepatocellular dedifferentiation. In hepatocellular carcinoma, coordinated downregulation of TRβ and DIO1 establishes a tumor-associated hypothyroid state that promotes metabolic reprogramming and tumor progression. The clinical relevance of TH signaling in MASLD has been underscored by the recent approval of Resmetirom, a liver-targeted TRβ‑selective agonist, for the treatment of non-cirrhotic MASH with moderate-to-severe fibrosis (F2-F3). This approval represents a landmark transition from mechanistic understanding to metabolism-centered precision therapy in MASLD. Clinical trials have demonstrated that Resmetirom not only improves key histological endpoints, including MASH resolution and fibrosis regression, but also favorably modulates atherogenic lipid profiles, highlighting the therapeutic potential of selectively targeting hepatic TH pathways. This review systematically summarizes the multidimensional regulatory roles of TH across the MASLD disease spectrum and discusses emerging diagnostic and therapeutic implications of TH-based interventions, aiming to inform future mechanistic research and optimize clinical management strategies.
2.Protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on a yorkshire model of brain injury after traumatic blood loss.
Xiang-Yu SONG ; Yang-Hui DONG ; Zhi-Bo JIA ; Lei-Jia CHEN ; Meng-Yi CUI ; Yan-Jun GUAN ; Bo-Yao YANG ; Si-Ce WANG ; Sheng-Feng CHEN ; Peng-Kai LI ; Heng CHEN ; Hao-Chen ZUO ; Zhan-Cheng YANG ; Wen-Jing XU ; Ya-Qun ZHAO ; Jiang PENG
Chinese Journal of Traumatology 2025;28(6):469-476
PURPOSE:
To investigate the protective effect of sub-hypothermic mechanical perfusion combined with membrane lung oxygenation on ischemic hypoxic injury of yorkshire brain tissue caused by traumatic blood loss.
METHODS:
This article performed a random controlled trial. Brain tissue of 7 yorkshire was selected and divided into the sub-low temperature anterograde machine perfusion group (n = 4) and the blank control group (n = 3) using the random number table method. A yorkshire model of brain tissue injury induced by traumatic blood loss was established. Firstly, the perfusion temperature and blood oxygen saturation were monitored in real-time during the perfusion process. The number of red blood cells, hemoglobin content, NA+, K+, and Ca2+ ions concentrations and pH of the perfusate were detected. Following perfusion, we specifically examined the parietal lobe to assess its water content. The prefrontal cortex and hippocampus were then dissected for histological evaluation, allowing us to investigate potential regional differences in tissue injury. The blank control group was sampled directly before perfusion. All statistical analyses and graphs were performed using GraphPad Prism 8.0 Student t-test. All tests were two-sided, and p value of less than 0.05 was considered to indicate statistical significance.
RESULTS:
The contents of red blood cells and hemoglobin during perfusion were maintained at normal levels but more red blood cells were destroyed 3 h after the perfusion. The blood oxygen saturation of the perfusion group was maintained at 95% - 98%. NA+ and K+ concentrations were normal most of the time during perfusion but increased significantly at about 4 h. The Ca2+ concentration remained within the normal range at each period. Glucose levels were slightly higher than the baseline level. The pH of the perfusion solution was slightly lower at the beginning of perfusion, and then gradually increased to the normal level. The water content of brain tissue in the sub-low and docile perfusion group was 78.95% ± 0.39%, which was significantly higher than that in the control group (75.27% ± 0.55%, t = 10.49, p < 0.001), and the difference was statistically significant. Compared with the blank control group, the structure and morphology of pyramidal neurons in the prefrontal cortex and CA1 region of the hippocampal gyrus were similar, and their integrity was better. The structural integrity of granulosa neurons was destroyed and cell edema increased in the perfusion group compared with the blank control group. Immunofluorescence staining for glail fibrillary acidic protein and Iba1, markers of glial cells, revealed well-preserved cell structures in the perfusion group. While there were indications of abnormal cellular activity, the analysis showed no significant difference in axon thickness or integrity compared to the 1-h blank control group.
CONCLUSIONS
Mild hypothermic machine perfusion can improve ischemia and hypoxia injury of yorkshire brain tissue caused by traumatic blood loss and delay the necrosis and apoptosis of yorkshire brain tissue by continuous oxygen supply, maintaining ion homeostasis and reducing tissue metabolism level.
Animals
;
Perfusion/methods*
;
Disease Models, Animal
;
Brain Injuries/etiology*
;
Swine
;
Male
;
Hypothermia, Induced/methods*
3.Clinical Significance of XPO1 High Expression in Diffuse Large B-Cell Lymphoma and Its Mechanism.
Jing ZHANG ; Yan GU ; Jia-Heng GUAN ; Xue WU ; Bao-An CHEN
Journal of Experimental Hematology 2025;33(2):393-406
OBJECTIVE:
To explore the expression and clinical significance of XPO1 in newly diagnosed adult diffuse large B-cell lymphoma (DLBCL), and further investigate its functional mechanism.
METHODS:
Immunohistochemical testing was conducted for XPO1 expression in 93 cases of DLBCL and 30 cases of reactive lymphoid hyperplasia. A risk model was construed to find survival related genes in DLBCL patients. Cell proliferation, apoptosis, and cell cycle assays were performed to explore the effect of XPO1 inhibitor (KPT-8602) and XPO1 knockdown. Differential expression gene (DEG) was examined based on the transcriptomes.
RESULTS
The expression of XPO1 in DLBCL patients was higher than that of the controls. Compared with XPO1 low-expression group, XPO1 high-expression group had a worse prognosis. The constructed risk model indicated that XPO1 and 14 genes in nucleocytoplasmic transport pathway (NTP) might be potential prediction marker of adverse outcome in DLBCL. Moreover, KPT-8602 as well as the XPO1 knockdown could inhibit cell proliferation, promote apoptosis, and induce cell cycle arrest in two DLBCL cell lines, Farage and SU-DHL-4. Based on the gene expression profiling in the datasets of DLBCL, patients were classified into XPO1 high and XPO1 low expression groups, and the MYBL1 was identified as the down-stream effector of XPO1. Inhibiting the function of XPO1 or reducing its expression can significantly decrease the expression of MYBL1 Conclusion: XPO1 is highly expressed in DLBCL, which is associated with poor prognosis. The oncogenic roles of the new XPO1/MYBL1 signaling are identified in DLBCL and XPO1 inhibitor may be a potential option for newly-diagnosed DLBCL patients.
Humans
;
Lymphoma, Large B-Cell, Diffuse/pathology*
;
Exportin 1 Protein
;
Karyopherins/metabolism*
;
Receptors, Cytoplasmic and Nuclear/metabolism*
;
Cell Proliferation
;
Apoptosis
;
Prognosis
;
Cell Line, Tumor
;
Clinical Relevance
4.The treatment of distal tibial giant cell tumor by local arthroplasty: a pilot study and a case report
Jiansheng ZHOU ; Jianzhong GUAN ; Heng ZHANG ; Hongyuan CHENG ; Zhonglian ZHU ; Kunzheng WANG
Chinese Journal of Orthopaedics 2025;45(14):954-959
A 20-year old female patient diagnosed with right distal tibial giant cell tumor underwent a surgery of resection of distal tibial giant cell tumor, residual cavity liquid nitrogen and electrocauterization inactivation and local arthroplasty on March 17, 2023. Preoperatively a life-size distal tibia model was 3D printed using polylactic acid (PLA) material based on the CT data of patient's distal tibia. Tumor resection was simulated on the model, preserving the surrounding normal bone and articular cartilage unaffected by the tumor. The residual cavity was filled with bone cement and the distal tibial articular surface was shaped using the talar articular surface as a template. The 3D CT data of bone cement was collected and reconstructed. The irregular bone and cartilage defect data were trimmed to form a regular arc shape, which was used as the data for fabricating local arthroplasty prosthesis. The local arthroplasty prosthesis composed of a titanium base and a VE polyethylene liner was 3D printed. During the operation, the test models of titanium alloy base and VE polyethylene liner were used to test the matching degree with the bone and cartilage defect. Minor adjustments were made by removing a portion of the lateral wall of the residual cavity and modifying the base height to achieve proper alignment of the distal tibial articular surface with the talar surface. After confirming a satisfactory fit, the local arthroplasty prosthesis was implanted. Intraoperative fluoroscopic confirmed accurate placement of the prosthesis, good anatomical match with the defect, and restoration of the joint line. The postoperative follow-up was conducted at 2, 4, 12, 20, 48, 72 and 92 weeks. Wound healing was closely monitored, along with radiologic assessment for prosthesis bone ingrowth and local tumor recurrence. Functional evaluations were performed using the AOFAS and Kofoed scoring systems. Postoperatively, the patient experienced plantar numbness and sensory disturbance, which gradually resolved after three weeks. Assisted ambulation began at two weeks postoperatively, and the patient resumed a normal gait by 12 weeks. The Mayo ankle arthroplasty evaluation criteria at postoperative at 48 weeks were excellent. The AOFAS score and Kofoed score were 97 points and 94 points respectively, indicating excellent functional outcomes. Postoperative X-ray indicated that no bone ingrowth was observed at 2 weeks and 4 weeks after the operation, minor ingrowth at 12 weeks postoperatively, significant bone ingrowth at 20 weeks, and complete osseointegration by 48 to 64 weeks. Postoperative CT imaging at 92 weeks confirmed full prosthesis osseointegration, while MRI at 72 weeks showed no evidence of tumor recurrence.
5.The treatment of distal tibial giant cell tumor by local arthroplasty: a pilot study and a case report
Jiansheng ZHOU ; Jianzhong GUAN ; Heng ZHANG ; Hongyuan CHENG ; Zhonglian ZHU ; Kunzheng WANG
Chinese Journal of Orthopaedics 2025;45(14):954-959
A 20-year old female patient diagnosed with right distal tibial giant cell tumor underwent a surgery of resection of distal tibial giant cell tumor, residual cavity liquid nitrogen and electrocauterization inactivation and local arthroplasty on March 17, 2023. Preoperatively a life-size distal tibia model was 3D printed using polylactic acid (PLA) material based on the CT data of patient's distal tibia. Tumor resection was simulated on the model, preserving the surrounding normal bone and articular cartilage unaffected by the tumor. The residual cavity was filled with bone cement and the distal tibial articular surface was shaped using the talar articular surface as a template. The 3D CT data of bone cement was collected and reconstructed. The irregular bone and cartilage defect data were trimmed to form a regular arc shape, which was used as the data for fabricating local arthroplasty prosthesis. The local arthroplasty prosthesis composed of a titanium base and a VE polyethylene liner was 3D printed. During the operation, the test models of titanium alloy base and VE polyethylene liner were used to test the matching degree with the bone and cartilage defect. Minor adjustments were made by removing a portion of the lateral wall of the residual cavity and modifying the base height to achieve proper alignment of the distal tibial articular surface with the talar surface. After confirming a satisfactory fit, the local arthroplasty prosthesis was implanted. Intraoperative fluoroscopic confirmed accurate placement of the prosthesis, good anatomical match with the defect, and restoration of the joint line. The postoperative follow-up was conducted at 2, 4, 12, 20, 48, 72 and 92 weeks. Wound healing was closely monitored, along with radiologic assessment for prosthesis bone ingrowth and local tumor recurrence. Functional evaluations were performed using the AOFAS and Kofoed scoring systems. Postoperatively, the patient experienced plantar numbness and sensory disturbance, which gradually resolved after three weeks. Assisted ambulation began at two weeks postoperatively, and the patient resumed a normal gait by 12 weeks. The Mayo ankle arthroplasty evaluation criteria at postoperative at 48 weeks were excellent. The AOFAS score and Kofoed score were 97 points and 94 points respectively, indicating excellent functional outcomes. Postoperative X-ray indicated that no bone ingrowth was observed at 2 weeks and 4 weeks after the operation, minor ingrowth at 12 weeks postoperatively, significant bone ingrowth at 20 weeks, and complete osseointegration by 48 to 64 weeks. Postoperative CT imaging at 92 weeks confirmed full prosthesis osseointegration, while MRI at 72 weeks showed no evidence of tumor recurrence.
6.Drug resistance and genetic diversity of clinical strains of Helicobacter pylori in the Qiannan Prefecture and Guiyang City,and their relationships with diseases
Yuan-Yuan ZHANG ; Ke PAN ; Meng-Heng MI ; Yu-Zhu GUAN ; Qiu-Dan LU ; Juan ZHENG ; Jin ZHANG ; Tian-Shu WANG ; Qi LIU ; Zheng-Hong CHEN
Chinese Journal of Zoonoses 2024;40(1):46-55
To understand Helicobacter pylori's drug resistance,genetic diversity,and relationship with clinical diseases in the Guiyang and Qiannan minority areas of Guizhou Province,we collected samples through endoscopy,and isolated and cul-tured H.pylori.The drug resistance and genotype characteristics were determined.The differences in different regions and dis-ease types were compared,and the structural characteristics of H.pylori and mixed infections with different strains of H.py-lori in Qiannan Prefecture were analyzed.A difference in the composition ratio of EPYIA typing in the cagA variable region was observed between the two areas(P=0.012),and the composition ratio of the vacA genotype differed(P=0.000).A total of 94.6%(53/56)new sequences of H.pylori strains from two regions were obtained by MLST.The rate of infection by H.pylori mixed with different strains was 44.4%in Qiannan Pre-fecture,and no significant difference was observed in the com-position of H.pylori mixed infections among patients with dif-ferent clinical diseases(P=0.349).Differences in EPI YA typ-ing and the vacA genotype composition ratio in the cagA varia-ble region of H.pylori were observed between the Qiannan Prefecture and Guiyang City.
7.Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome (version 2024)
Junyu WANG ; Hai JIN ; Danfeng ZHANG ; Rutong YU ; Mingkun YU ; Yijie MA ; Yue MA ; Ning WANG ; Chunhong WANG ; Chunhui WANG ; Qing WANG ; Xinyu WANG ; Xinjun WANG ; Hengli TIAN ; Xinhua TIAN ; Yijun BAO ; Hua FENG ; Wa DA ; Liquan LYU ; Haijun REN ; Jinfang LIU ; Guodong LIU ; Chunhui LIU ; Junwen GUAN ; Rongcai JIANG ; Yiming LI ; Lihong LI ; Zhenxing LI ; Jinglian LI ; Jun YANG ; Chaohua YANG ; Xiao BU ; Xuehai WU ; Li BIE ; Binghui QIU ; Yongming ZHANG ; Qingjiu ZHANG ; Bo ZHANG ; Xiangtong ZHANG ; Rongbin CHEN ; Chao LIN ; Hu JIN ; Weiming ZHENG ; Mingliang ZHAO ; Liang ZHAO ; Rong HU ; Jixin DUAN ; Jiemin YAO ; Hechun XIA ; Ye GU ; Tao QIAN ; Suokai QIAN ; Tao XU ; Guoyi GAO ; Xiaoping TANG ; Qibing HUANG ; Rong FU ; Jun KANG ; Guobiao LIANG ; Kaiwei HAN ; Zhenmin HAN ; Shuo HAN ; Jun PU ; Lijun HENG ; Junji WEI ; Lijun HOU
Chinese Journal of Trauma 2024;40(5):385-396
Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.
8.Relationship and clinical significance of ctDNA methylation and postoperative recurrence of thyroid cancer
Xin-Yu LIU ; Heng-Guan CUI ; Ting ZHOU ; Xiao-Liang WANG ; Wei-Xing SHEN
Chinese Journal of Current Advances in General Surgery 2024;27(8):618-621
Objective:To investigate the relationship and clinical significance of circulating tu-mor DNA(ctDNA)methylation with postoperative recurrence of thyroid cancer.Method:5 pa-tients with recurrent thyroid cancer in our hospital from March 2021 to April 2022 were selected as the observation group,and 2 healthy volunteers were selected as the control group.The level of ctDNA methylation in peripheral blood of the two groups was detected by Illumina high-throughput sequencing system.Gene ontology(GO)function analysis and Kyoto gene and genome encyclope-dia(KEGG)signal pathway analysis were carried out on the methylation region genes with signifi-cant differences through the DAVID gene function analysis platform.Result:There were 7787 dif-ferential ctDNA methylation sites between the two groups.2914(37.4%)were hypermethylation sites and 4873(62.6%)were low methylation sites.GO functional analysis showed that differentially methylated genes were enriched in molecular functions such as DNA-binding transcriptional acti-vation,cell-substrate adhesion,glycoprotein complex and other cellular components.KEGG path-way analysis showed that differentially methylated genes were enriched in thyroid carcinoma signal pathway,cell adhesion molecules,RAP1 signal pathway,RAS signal pathway,MAPK signal path-way and so on.Conclusion:ctDNA methylation may be involved in cancer recurrence in postop-erative patients with thyroid cancer.Monitoring the level of ctDNA methylation in peripheral blood may be an effective method to indicate the recurrence or metastasis of thyroid cancer and guide clinical diagnosis and treatment.
9.Primary central nervous system T-cell lymphoma in children and adolescents: a clinicopathological analysis of five cases.
Pei Zhu HU ; Heng Yan ZHANG ; Guan Nan WANG ; Wu Gan ZHAO ; Dan Dan ZHANG ; Wen Cai LI
Chinese Journal of Pathology 2023;52(1):37-42
Objective: To study the clinicopathological characteristics, and further understand primary central nervous system T-cell lymphoma (PCNSTCL) in children and adolescents. Methods: Five cases of PCNSTCL in children and adolescents were collected from December 2016 to December 2021 at the First Affiliated Hospital of Zhengzhou University. The clinicopathological characteristics, immunophenotypic, and molecular pathologic features were analyzed, and relevant literatures reviewed. Results: There were two male and three female patients with a median age of 14 years (range 11 to 18 years). There were two peripheral T-cell lymphomas, not otherwise specified, two anaplastic large cell lymphoma, ALK-positive and one NK/T cell lymphoma. Pathologically, the tumor cells showed a variable histomorphologic spectrum, including small, medium and large cells with diffuse growth pattern and perivascular accentuation. Immunohistochemistry and in situ hybridization showed CD3 expression in four cases, and CD3 was lost in one case. CD5 expression was lost in four cases and retained in one case. ALK and CD30 were expressed in two cases. One tumor expressed CD56 and Epstein-Barr virus-encoded RNA. All cases showed a cytotoxic phenotype with expression of TIA1 and granzyme B. Three cases had a high Ki-67 index (>50%). T-cell receptor (TCR) gene rearrangement was clonal in two cases. Conclusions: PCNSTCL is rare, especially in children and adolescents. The morphology of PCNSTCL is diverse. Immunohistochemistry and TCR gene rearrangement play important roles in the diagnosis.
Female
;
Humans
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Male
;
Central Nervous System/pathology*
;
Central Nervous System Neoplasms/pathology*
;
Epstein-Barr Virus Infections
;
Herpesvirus 4, Human
;
Lymphoma, T-Cell/pathology*
;
Lymphoma, T-Cell, Peripheral/genetics*
;
Receptor Protein-Tyrosine Kinases/genetics*
;
Receptors, Antigen, T-Cell
;
Child
;
Adolescent
10.Application and research progress of artificial intelligence technology in trauma treatment.
Heng ZHANG ; Xiaodong MA ; Jiaqin WANG ; Jianzhong GUAN ; Kuanxin LI ; Jianning ZHAO ; Jiansheng ZHOU
Chinese Journal of Reparative and Reconstructive Surgery 2023;37(11):1431-1437
OBJECTIVE:
To review the application and research progress of artificial intelligence (AI) technology in trauma treatment.
METHODS:
The recent research literature on the application of AI and related technologies in trauma treatment was reviewed and summarized in terms of prehospital assistance, in-hospital emergency care, and post-traumatic stress disorder risk regression prediction, meanwhile, the development trend of AI technology in trauma treatment were outlooked.
RESULTS:
The AI technology can rapidly analyze and manage large amount of clinical data to help doctors identify patients' situation of trauma and predict the risk of possible complications more accurately. The application of AI technology in surgical assistance and robotic operations can achieve precise surgical plan and treatment, reduce surgical risks, and shorten the operation time, so as to improve the efficiency and long-term effectiveness of the trauma treatment.
CONCLUSION
There is a promising future for the application of AI technology in the trauma treatment. However, it is still in the stage of exploration and development, and there are many difficulties of historical data bias, application condition limitations, as well as ethical and moral issues need to be solved.
Humans
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Artificial Intelligence
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Operative Time
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Robotic Surgical Procedures
;
Technology

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