1.The Role of Lysosomal Dysfunction in Hepatocellular Carcinoma: From Pathogenesis to Targeted Therapies
Yue-Yan WU ; Xin CHEN ; Ce-Fan ZHOU ; Jing-Feng TANG ; Rui ZHANG
Progress in Biochemistry and Biophysics 2026;53(3):609-622
Hepatocellular carcinoma (HCC) is a lethal cancer with high morbidity rates worldwide. It is a major threat to public health in China, due to the combination of known and new risk factors, such as endemic hepatitis B virus (HBV), dietary aflatoxin exposure, and the occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD). Although many methods for surveillance and multimodal therapies, such as surgery, local ablation, transarterial therapy, and new systemic agents, have been available, the survival rates of HCC remains poor. They have very limited durable responses, long post-treatment recurrence rates, and high resistance to treatment. This reflects an imperfect picture of the biological cause of the disease and a need for new mechanistic or targeted techniques. A significant characteristic of HCC, in common with other aggressive cancers, is the presence of reprogrammed, hyperactive cell metabolism. Tumor cells hijack metabolic pathways to promote their uncontrolled growth, stress survival, invasion and metastasis. While classical mechanisms such as the Warburg effect, lipid metabolism and glutamine utilization have been understood, the lysosome, which was once viewed as a static “waste disposal unit” to remove old organelles and proteins, is instead a dynamic signaling and metabolic core. The lysosomes incorporate nutrients, energy and stress signals by master regulators such as mTORC1 (activated on its surface) that balance anabolic growth and catabolic recycling to the cellular demands. In HCC, lysosomes are not passive, but are highly active and dysregulated. HCC cells upregulate lysosomes, which scavenge intracellular components via enhanced autophagy and engulf extracellular proteins via macropinocytosis, crucial for survival in the nutrient-poor, hypoxic tumor microenvironment. In addition to metabolism, lysosomes exhibit pro-invasive functions by secreting hydrolases to remodel the extracellular matrix, promote angiogenesis, and suppress stromal immune cells to foster a pro-tumor microenvironment. In a clinical context, lysosomes play an important role in therapeutic resistance: they sequester and inactivate chemotherapeutics via lysosomal sequestration, and enhanced autophagic flux protects the cell from therapy-induced damage, contributing to relapse, as lysosomal dysfunction is a key cause of treatment failure. This makes lysosomes promising yet challenging therapeutic targets in HCC. Recent preclinical and early clinical studies investigate multiple strategies to exploit the susceptibility of lysosomes: lysosome-specific agents, alkalinizing the lysosome lumen or inducing membrane permeabilization and lysosome-dependent cell death; pharmacological inhibition of key lysosomal enzymes or autophagy to impair nutrient recycling and stress adaptation; smart nanotherapeutic agents or antibody-drug conjugates, specifically activated in the acidic lysosomal environment or utilizing lysosomal pathways for efficient intracellular drug release; and combination strategies of lysosome-targeting agents with tyrosine kinase inhibitors or immunotherapy to overcome resistance and achieve synergistic antitumor effects. In summary, our review systematically presents the role of lysosomes in HCC, from metabolic reprogramming and microenvironmental adaptation to therapeutic resistance. By synthesizing the latest mechanistic insights and preclinical advances, this review highlights the indispensable role of lysosomes in the complex HCC biological network, emphasizing that an in-depth understanding of this dynamic organelle holds great promise for developing innovative, targeted therapies, offering new hope for improving the poor prognosis of global HCC patients.
2.Expert consensus on early orthodontic treatment of class III malocclusion.
Xin ZHOU ; Si CHEN ; Chenchen ZHOU ; Zuolin JIN ; Hong HE ; Yuxing BAI ; Weiran LI ; Jun WANG ; Min HU ; Yang CAO ; Yuehua LIU ; Bin YAN ; Jiejun SHI ; Jie GUO ; Zhihua LI ; Wensheng MA ; Yi LIU ; Huang LI ; Yanqin LU ; Liling REN ; Rui ZOU ; Linyu XU ; Jiangtian HU ; Xiuping WU ; Shuxia CUI ; Lulu XU ; Xudong WANG ; Songsong ZHU ; Li HU ; Qingming TANG ; Jinlin SONG ; Bing FANG ; Lili CHEN
International Journal of Oral Science 2025;17(1):20-20
The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans
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Malocclusion, Angle Class III/classification*
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Orthodontics, Corrective/methods*
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Consensus
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Child
3.Application of OpenSim musculoskeletal model in biomechanics research of orthopedics and traumatology.
Rui LI ; Yang LIU ; Zhao-Jie ZHANG ; Xin-Wei ZHANG ; Yan-Zhen ZHANG ; Yan-Qi HU ; Can YANG ; Shu-Shi MAO ; Jia-Ming QIU
China Journal of Orthopaedics and Traumatology 2025;38(3):319-324
OpenSim is an open source, free motion simulation and gait analysis software, which can be used to dynamically simulate and analyze the complex motion of the human body, and is widely used in human biomechanical research. Since OpenSim can analyze multi-dimensional motion data such as muscle strength, joint torque, and muscle synergistic activation during human movement, it can be used to study the biomechanical mechanism of musculoskeletal imbalance diseases and various treatment methods in TCM orthopedics, and has a broad application prospect in the field of TCM orthopedics. By the analysis of the basic characteristics, elements, analysis process, and application prospects of OpenSim, it is concluded that OpenSim musculoskeletal model has a large application space in the field of traditional Chinese medicine orthopedic, which is helpful to explain the pathogenesis and mechanism of diseases, and promote the precision diagnosis and treatment of orthopedics diseases;the application of OpenSim musculoskeletal model can solve the problem that the previous research paid attention to the bone malalignment and not enough attention to the tendon, and provide a new method for the research of orthopedic diseases. At present, there are still problems in the promotion and application of OpenSim, such as large equipment requirements and high operation threshold. Therefore, multidisciplinary cooperation, clinical research, and data sharing are the basic research strategies in this field.
Humans
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Biomechanical Phenomena
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Orthopedics
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Traumatology
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Software
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Medicine, Chinese Traditional
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Musculoskeletal System
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Models, Biological
4.Study on the influence of the sY1192 gene locus in the AZFb/c region on sperm quality and pregnancy outcome.
Gang-Xin CHEN ; Yan SUN ; Rui YANG ; Zhi-Qing HUANG ; Hai-Yan LI ; Bei-Hong ZHENG
Asian Journal of Andrology 2025;27(2):231-238
Y chromosome microdeletions are an important cause of male infertility. At present, research on the Y chromosome is mainly focused on analyzing the loss of large segments of the azoospermia factor a/b/c (AZFa/b/c) gene, and few studies have reported the impact of unit point deletion in the AZF band on fertility. This study analyzed the effect of sperm quality after sY1192 loss in 116 patients. The sY1192-independent deletion accounted for 41.4% (48/116). Eight patterns were found in the deletions associated with sY1192. The rate of sperm detection was similar in the semen of patients with the independent sY1192 deletion and the combined sY1192 deletions (52.1% vs 50.0%). The patients with only sY1192 gene loss had a higher probability of sperm detection than the patients whose sY1192 gene locus existed, but other gene loci were lost (52.1% vs 32.0%). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus. After multiple intracytoplasmic sperm injection (ICSI) attempts, the pregnancy rate of spouses of men with sY1192-independent deletions was similar to that of other types of microdeletions, but the fertilization and cleavage rates were higher. We observed that eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. After ICSI, the fertilization rate and cleavage rate of the sY1192-independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no significant difference in pregnancy outcomes.
Humans
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Female
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Pregnancy
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Male
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Chromosomes, Human, Y/genetics*
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Adult
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Chromosome Deletion
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Pregnancy Outcome/genetics*
;
Infertility, Male/genetics*
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Spermatozoa/physiology*
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Semen Analysis
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Sex Chromosome Disorders of Sex Development/genetics*
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Sperm Injections, Intracytoplasmic
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Azoospermia/genetics*
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Sex Chromosome Aberrations
5.Explanation and interpretation of blood transfusion provisions for children with hematological diseases in the national health standard "Guideline for pediatric transfusion".
Ming-Yi ZHAO ; Rong HUANG ; Rong GUI ; Qing-Nan HE ; Ming-Yan HEI ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jin-Ping LIU ; Jing WANG ; Zhi-Li SHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Ming-Hua YANG
Chinese Journal of Contemporary Pediatrics 2025;27(1):18-25
To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura. This article presents the evidence and interpretation of the blood transfusion provisions for children with hematological diseases in the "Guideline for pediatric transfusion", aiming to assist in the understanding and implementing the blood transfusion section of this guideline.
Humans
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Child
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Hematologic Diseases/therapy*
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Blood Transfusion/standards*
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Practice Guidelines as Topic
6.Explanation and interpretation of the compilation of blood transfusion provisions for children undergoing hematopoietic stem cell transplantation in the national health standard "Guideline for pediatric transfusion".
Rong HUANG ; Qing-Nan HE ; Ming-Yan HEI ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jin-Ping LIU ; Jing WANG ; Zhi-Li SHAO ; Ming-Yi ZHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Rong GUI ; Ming-Hua YANG
Chinese Journal of Contemporary Pediatrics 2025;27(2):139-143
To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion for children undergoing hematopoietic stem cell transplantation is highly complex and challenging. This guideline provides recommendations on transfusion thresholds and the selection of blood components for these children. This article presents the evidence and interpretation of the transfusion provisions for children undergoing hematopoietic stem cell transplantation, with the aim of enhancing the understanding and implementation of the "Guideline for pediatric transfusion".
Humans
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Hematopoietic Stem Cell Transplantation
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Child
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Blood Transfusion/standards*
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Practice Guidelines as Topic
7.Explanation and interpretation of blood transfusion provisions for critically ill and severely bleeding pediatric patients in the national health standard "Guideline for pediatric transfusion".
Rong HUANG ; Qing-Nan HE ; Ming-Yan HEI ; Ming-Hua YANG ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jin-Ping LIU ; Jing WANG ; Zhi-Li SHAO ; Ming-Yi ZHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Rong GUI
Chinese Journal of Contemporary Pediatrics 2025;27(4):395-403
To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Critically ill children often present with anemia and have a higher demand for transfusions compared to other pediatric patients. This guideline provides guidance and recommendations for blood transfusions in cases of general critical illness, septic shock, acute brain injury, extracorporeal membrane oxygenation, non-life-threatening bleeding, and hemorrhagic shock. This article interprets the background and evidence of the blood transfusion provisions for critically ill and severely bleeding children in the "Guideline for pediatric transfusion", aiming to enhance understanding and implementation of this aspect of the guidelines. Citation:Chinese Journal of Contemporary Pediatrics, 2025, 27(4): 395-403.
Humans
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Critical Illness
;
Blood Transfusion/standards*
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Child
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Hemorrhage/therapy*
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Practice Guidelines as Topic
8.Explanation and interpretation of blood transfusion provisions for children undergoing cardiac surgery in the national health standard "Guideline for pediatric transfusion".
Rong HUANG ; Qing-Nan HE ; Ming-Yan HEI ; Ming-Hua YANG ; Xiao-Fan ZHU ; Jun LU ; Xiao-Jun XU ; Tian-Ming YUAN ; Rong ZHANG ; Xu WANG ; Jing WANG ; Zhi-Li SHAO ; Ming-Yi ZHAO ; Yong-Jian GUO ; Xin-Yin WU ; Jia-Rui CHEN ; Qi-Rong CHEN ; Jia GUO ; Rong GUI ; Jin-Ping LIU
Chinese Journal of Contemporary Pediatrics 2025;27(7):778-785
To guide clinical blood transfusion practices in pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Children undergoing cardiac surgery are at high risk of bleeding, and the causes of perioperative anemia and coagulation disorders in neonates and children are complex and varied, often necessitating the transfusion of allogeneic blood components. This guideline provides direction and recommendations for specific measures in blood management for children undergoing cardiac surgery before, during, and after surgery. This article interprets the background and evidence for the formulation of the blood transfusion provisions for children undergoing cardiac surgery, hoping to facilitate the understanding and implementation of this guideline.
Humans
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Cardiac Surgical Procedures
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Blood Transfusion/standards*
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Child
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Practice Guidelines as Topic
9.Clinical Features, Prognostic Analysis and Predictive Model Construction of Central Nervous System Invasion in Peripheral T-Cell Lymphoma.
Ya-Ting MA ; Yan-Fang CHEN ; Zhi-Yuan ZHOU ; Lei ZHANG ; Xin LI ; Xin-Hua WANG ; Xiao-Rui FU ; Zhen-Chang SUN ; Yu CHANG ; Fei-Fei NAN ; Ling LI ; Ming-Zhi ZHANG
Journal of Experimental Hematology 2025;33(3):760-768
OBJECTIVE:
To investigate the clinical features and prognosis of central nervous system (CNS) invasion in peripheral T-cell lymphoma (PTCL) and construct a risk prediction model for CNS invasion.
METHODS:
Clinical data of 395 patients with PTCL diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from 1st January 2013 to 31st December 2022 were analyzed retrospectively.
RESULTS:
The median follow-up time of 395 PTCL patients was 24(1-143) months. There were 13 patients diagnosed CNS invasion, and the incidence was 3.3%. The risk of CNS invasion varied according to pathological subtype. The incidence of CNS invasion in patients with anaplastic large cell lymphoma (ALCL) was significantly higher than in patients with angioimmunoblastic T-cell lymphoma (AITL) (P <0.05). The median overall survival was significantly shorter in patients with CNS invasion than in those without CNS involvement, with a median survival time of 2.4(0.6-127) months after diagnosis of CNS invasion. The results of univariate and multivariate analysis showed that more than 1 extranodal involvement (HR=4.486, 95%CI : 1.166-17.264, P =0.029), ALCL subtype (HR=9.022, 95%CI : 2.289-35.557, P =0.002) and ECOG PS >1 (HR=15.890, 95%CI : 4.409-57.262, P <0.001) were independent risk factors for CNS invasion in PTCL patients. Each of these risk factors was assigned a value of 1 point and a new prediction model was constructed. It could stratify the patients into three distinct groups: low-risk group (0-1 point), intermediate-risk group (2 points) and high-risk group (3 points). The 1-year cumulative incidence of CNS invasion in the high-risk group was as high as 50.0%. Further evaluation of the model showed good discrimination and accuracy, and the consistency index was 0.913 (95%CI : 0.843-0.984).
CONCLUSION
The new model shows a precise risk assessment for CNS invasion prediction, while its specificity and sensitivity need further data validation.
Humans
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Lymphoma, T-Cell, Peripheral/pathology*
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Prognosis
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Retrospective Studies
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Central Nervous System Neoplasms/pathology*
;
Neoplasm Invasiveness
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Male
;
Female
;
Central Nervous System/pathology*
;
Middle Aged
;
Adult
10.Risk factors and their diagnostic efficacy of perioperative lower limb deep venous thrombosis in polytrauma patients with predominant severe limb trauma
Xiao YANG ; Jimin CAI ; Xin GE ; Yan WANG ; Weiya ZHOU ; Yongjun RUI
Chinese Journal of Trauma 2025;41(8):764-772
Objective:To investigate the risk factors and their diagnostic efficacy of perioperative lower limb deep vein thrombosis (DVT) in polytrauma patients with predominant severe limb trauma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 155 polytrauma patients with predominant severe trauma who were admitted to Wuxi Ninth People′s Hospital from January 2021 to December 2024, including 64 males and 91 females, aged 13-95 years [(52.1±16.9)years]. Abbreviated injury scale (AIS) was 5-15 points [(7.4±2.1)points] and injury severity score (ISS) was 17-59 points [(21.3±6.5)points]. Based on the occurrence of DVT in the perioperative period, the patients were divided into preoperative DVT group with 17 patients (11.0%) and non-preoperative DVT group with 138 patients (89.0%) as well as postoperative DVT group with 24 patients (15.5%) and non-postoperative DVT group with 131 patients (84.5%). Basic clinical data were collected, including gender, age, body mass index (BMI), underlying diseases (hypertension, diabetes mellitus), hemoglobin level (Hb), platelet count (PLT), D-dimer, ISS, trauma site [cranial and brain trauma, thoracic and abdominal trauma, upper limb trauma, lower limb trauma (femoral fracture, patellar fracture, tibial or fibular fracture, foot fracture, vascular injury), and pelvic fracture], preoperative waiting time for surgery, surgical site (pelvis and lower limb, other areas), surgical protocols (pelvic and lower limb internal fixation, external fixation of lower limb, lower limb amputation), operation duration less or more than 2 hours, amount of intraoperative blood loss, intraoperative blood transfusion requirement, venous thromboembolism (VTE) prophylaxis (pharmacological and mechanical modalities) and length of hospital stay. Univariate analysis and multivariate binary Logistic regression analysis were conducted to investigate the correlation between the aforementioned indicators and incidence of perioperative lower limb DVT in polytrauma patients with predominant severe limb trauma and determine the independent risk factors. Receiver operating characteristic (ROC) curve and area under the curve (AUC) of the relevant risk factors were analyzed to evaluate and compare the diagnostic efficacy of the risk factors for perioperative lower limb DVT in polytrauma patients with predominant severe limb trauma.Results:Univariate analysis results showed that age, history of hypertension, D-dimer, thoracic and abdominal trauma, pelvic fracture, preoperative waiting time for surgery, and length of hospital stay were significantly correlated with preoperative of DVT of the lower limbs in the patients ( P<0.05). The results of multivariate binary Logistic regression analysis showed that age ( OR=1.05, 95% CI 1.00, 1.10, P<0.05), pelvic fracture ( OR=5.03, 95% CI 1.09, 23.20, P<0.05), preoperative waiting time for surgery ( OR=1.10, 95% CI 1.00, 1.22, P<0.05) and length of hospital stay ( OR=0.89,95% CI 0.81,0.98, P<0.05) were highly correlated with preoperative DVT of the lower limbs in the patients ( P<0.05). Univariate analysis results showed that age, D-dimer, ISS, foot fracture, and length of hospital stay were significantly correlated with postoperative DVT of the lower limbs in the patients ( P<0.05). The results of multivariate binary Logistic regression analysis showed that age ( OR=1.05, 95% CI 1.01, 1.08, P<0.01), D-dimer ( OR=1.05, 95% CI 1.00, 1.10, P<0.05), ISS ( OR=1.09, 95% CI 1.01, 1.17, P<0.05), and foot fracture ( OR=3.51 , 95% CI 1.25 , 9.87 , P<0.05) were significantly correlated with postoperative DVT of the lower limbs in the patients ( P<0.05). The results of the ROC curve analysis indicated that preoperative waiting time for surgery (AUC=0.83, 95% CI 0.75, 0.91) had the highest diagnostic efficacy for preoperative DVT of the lower limbs in the patients, with the diagnostic efficacies of pelvic fracture (AUC=0.75, 95% CI 0.65, 0.85) and age (AUC=0.70, 95% CI 0.59, 0.82) decreasing successively. For postoperative DVT of the lower limbs in the patients, D-dimer (AUC=0.71, 95% CI 0.61, 0.81) exhibited the highest diagnostic efficacy, followed by age (AUC=0.70, 95% CI 0.59, 0.81), ISS (AUC=0.64, 95% CI 0.51, 0.76) and foot fracture (AUC=0.62, 95% CI 0.49, 0.74), with diagnostic efficacy decreased successively. Conclusions:For polytrauma patients with predominant severe limb trauma, age, pelvic fracture and preoperative waiting time for surgery are independent risk factors for preoperative DVT, while age, D-dimer, ISS and foot fracture are independent risk factors for postoperative DVT. Additionally, preoperative waiting time for surgery has the best diagnostic efficacy for preoperative DVT, followed by pelvic fracture and age. D-dimer has the best diagnostic efficacy for postoperative DVT, followed by age, ISS and foot fracture.

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