Trauma diagnostic-related target proteins and their detection techniques.

Trauma is a significant health issue that not only leads to immediate death in many cases but also causes severe complications, such as sepsis, thrombosis, haemorrhage, acute respiratory distress syndrome and traumatic brain injury, among trauma patients. Target protein identification technology is a vital technique in the field of biomedical research, enabling the study of biomolecular interactions, drug discovery and disease treatment. It plays a crucial role in identifying key protein targets associated with specific diseases or biological processes, facilitating further research, drug design and the development of treatment strategies. The application of target protein technology in biomarker detection enables the timely identification of newly emerging infections and complications in trauma patients, facilitating expeditious medical interventions and leading to reduced post-trauma mortality rates and improved patient prognoses. This review provides an overview of the current applications of target protein identification technology in trauma-related complications and provides a brief overview of the current target protein identification technology, with the aim of reducing post-trauma mortality, improving diagnostic efficiency and prognostic outcomes for patients.

Quasi-Chromophores Segregated by Single-Chain Nanoparticles of Fluorinated Zwitterionic Random Copolymers Showing Remarkably Enhanced Fluorescence Emission Capable of Fluorescent Cell Imaging.

Organic and polymer fluorescent nanomaterials are a frontier research focus. Here in this work, a series of fluorinated zwitterionic random copolymers end-attached with a quasi-chromophoric group of pyrene or tetraphenylethylene (TPE) are well synthesized via atom transfer radical polymerization with activators regenerated by electron transfer (ARGET ATRP). Those random copolymers with total degree of polymerization 100 or 200 are able to produce fluorescent single-chain nanoparticles (SCNPs) through intra-chain self-folding assembly with quite uniform diameters in the range of 10-20 nm as characterized by dynamic light scattering and transmission electron microscopy. By virtue of the segregation or confinement effect, both SCNPs functionalized with pyrene or TPE group are capable of emitting fluorescence, with pyrene tethered SCNPs exhibiting stronger fluorescence emission reaching the highest quantum yield ≈20%. Moreover, such kind of fluorescent SCNPs manifest low cytotoxicity and good cell imaging performance for Hela cells. The creation of fluorescent SCNPs through covalently attached one quasi-chromophore to the end of one fluorinated zwitterionic random copolymer provides an alternative strategy for preparing polymeric luminescence nanomaterials, promisingly serving as a new type of fluorescent nanoprobes for biological imaging applications.

Predictors of mortality in patients with isolated gastrointestinal perforation.

Gastrointestinal (GI) perforation is common in the emergency department and has a high mortality rate. The present study aimed to identify risk factors for mortality in patients with GI perforation. The objective was to assess and prognosticate the surgical outcomes of patients, aiming to ascertain the efficacy of the procedure for individual patients. A retrospective cohort study of patients with GI perforation who underwent surgery in a public tertiary hospital in China from January 2012 to June 2022 was performed. Demographics, clinical characteristics, laboratory and imaging results, and outcomes were collected from electronic medical records. The primary outcome measure was in-hospital mortality, and patients were divided into survivor and non-survivor groups based on this measure. Univariate and multivariable logistic regression analyses were performed to obtain independent factors associated with mortality. A total of 529 patients with GI perforation were eligible for inclusion. The in-hospital mortality rate after emergency surgery was 10.59%. The median age of the patients was 60 years (interquartile range, 44-72 years). Multivariable logistic regression analysis indicated that age, shock on admission, elevated serum creatinine (sCr) and white blood cell (WBC) count <3.5x109 or >20x109 cells/l were predictors of in-hospital mortality. In conclusion, advanced age, shock on admission, elevated sCr levels and significantly abnormal WBC count are associated with higher in-hospital mortality following emergency laparotomy.

Molecular Mechanism of Mutational Disruption of DCLK1 Autoinhibition Provides a Rationale for Inhibitor Screening.

Doublecortin-like kinase 1 (DCLK1) is a prominent kinase involved in carcinogenesis, serving as a diagnostic marker for early cancer detection and prevention, as well as a target for cancer therapy. Extensive research efforts have been dedicated to understanding its role in cancer development and designing selective inhibitors. In our previous work, we successfully determined the crystal structure of DCLK1 while it was bound to its autoinhibitory domain (AID) at the active site. By analyzing this structure, we were able to uncover the intricate molecular mechanisms behind specific cancer-causing mutations in DCLK1. Utilizing molecular dynamics simulations, we discovered that these mutations disrupt the smooth assembly of the AID, particularly affecting the R2 helix, into the kinase domain (KD). This disruption leads to the exposure of the D533 residue of the DFG (Asp-Phe-Gly) motif in the KD, either through steric hindrance, the rearrangement of electrostatic interactions, or the disruption of local structures in the AID. With these molecular insights, we conducted a screening process to identify potential small-molecule inhibitors that could bind to DCLK1 through an alternative binding mode. To assess the binding affinity of these inhibitors to the KD of DCLK1, we performed calculations on their binding energy and conducted SPR experiments. We anticipate that our study will contribute novel perspectives to the field of drug screening and optimization, particularly in targeting DCLK1.

Multimodal analysis of cell-free DNA whole-methylome sequencing for cancer detection and localization.

Multimodal epigenetic characterization of cell-free DNA (cfDNA) could improve the performance of blood-based early cancer detection. However, integrative profiling of cfDNA methylome and fragmentome has been technologically challenging. Here, we adapt an enzyme-mediated methylation sequencing method for comprehensive analysis of genome-wide cfDNA methylation, fragmentation, and copy number alteration (CNA) characteristics for enhanced cancer detection. We apply this method to plasma samples of 497 healthy controls and 780 patients of seven cancer types and develop an ensemble classifier by incorporating methylation, fragmentation, and CNA features. In the test cohort, our approach achieves an area under the curve value of 0.966 for overall cancer detection. Detection sensitivity for early-stage patients achieves 73% at 99% specificity. Finally, we demonstrate the feasibility to accurately localize the origin of cancer signals with combined methylation and fragmentation profiling of tissue-specific accessible chromatin regions. Overall, this proof-of-concept study provides a technical platform to utilize multimodal cfDNA features for improved cancer detection.

Multidimensional Analysis of a Cell-Free DNA Whole Methylome Sequencing Assay for Early Detection of Gastric Cancer: Protocol for an Observational Case-Control Study.

BACKGROUND: Commonly used noninvasive serological indicators serve as a step before endoscope diagnosis and help identify the high-risk gastric cancer (GC) population. However, they are associated with high false positives and high false negatives. Alternative noninvasive approaches, such as cancer-related features in cell-free DNA (cfDNA) fragments, have been gradually identified and play essential roles in early cancer detection. The integrated analysis of multiple cfDNA features has enhanced detection sensitivity compared to individual features. OBJECTIVE: This study aimed to develop and validate an assay based on assessing genomic-scale methylation and fragmentation profiles of plasma cfDNA for early cancer detection, thereby facilitating the early diagnosis of GC. The primary objective is to evaluate the overall specificity and sensitivity of the assay in predicting GC within the entire cohort, and subsequently within each clinical stage of GC. The secondary objective involved investigating the specificity and sensitivity of the assay in combination with possible serological indicators. METHODS: This is an observational case-control study. Blood samples will be prospectively collected before gastroscopy from 180 patients with GC and 180 nonmalignant control subjects (healthy or with benign gastric diseases). Cases and controls will be randomly divided into a training and a testing data set at a ratio of 2:1. Plasma cfDNA will be isolated and extracted, followed by bisulfite-free low-depth whole methylome sequencing. A multidimensional model named Thorough Epigenetic Marker Integration Solution (THEMIS) will be constructed in the training data set. The model includes features such as the methylated fragment ratio, chromosomal aneuploidy of featured fragments, fragment size index, and fragment end motif. The performance of the model in distinguishing between patients with cancer and noncancer controls will then be evaluated in the testing data set. Furthermore, GC-related biomarkers, such as pepsinogen, gastrin-17, and Helicobacter pylori, will be measured for each patient, and their predictive accuracy will be assessed both independently and in combination with the THEMIS model. RESULTS: Recruitment began in November 2022 and will be ended in April 2024. As of August 2022,250 patients have been enrolled. The final data analysis is anticipated to be completed by September 2024. CONCLUSIONS: This is the first registered case-control study designed to investigate a stacked ensemble model integrating several cfDNA features generated from a bisulfite-free whole methylome sequencing assay. These features include methylation patterns, fragmentation profiles, and chromosomal copy number changes, with the aim of identifying the GC population. This study will determine whether multidimensional analysis of cfDNA will prove to be an effective strategy for distinguishing patients with GC from nonmalignant individuals within the Chinese population. We anticipate the THEMIS model will complement the standard-of-care screening and aid in identifying high-risk patients for further diagnosis. TRIAL REGISTRATION: ClinicalTrial.gov NCT05668910; https://www.clinicaltrials.gov/study/NCT05668910. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48247.

[MinerVa: A high performance bioinformatic algorithm for the detection of minimal residual disease in solid tumors].

How to improve the performance of circulating tumor DNA (ctDNA) signal acquisition and the accuracy to authenticate ultra low-frequency mutation are major challenges of minimal residual disease (MRD) detection in solid tumors. In this study, we developed a new MRD bioinformatics algorithm, namely multi-variant joint confidence analysis (MinerVa), and tested this algorithm both in contrived ctDNA standards and plasma DNA samples of patients with early non-small cell lung cancer (NSCLC). Our results showed that the specificity of multi-variant tracking of MinerVa algorithm ranged from 99.62% to 99.70%, and when tracking 30 variants, variant signals could be detected as low as 6.3 × 10 -5 variant abundance. Furthermore, in a cohort of 27 NSCLC patients, the specificity of ctDNA-MRD for recurrence monitoring was 100%, and the sensitivity was 78.6%. These findings indicate that the MinerVa algorithm can efficiently capture ctDNA signals in blood samples and exhibit high accuracy in MRD detection.

Identification of genetic and immune signatures for the recurrence of HER2-positive breast cancer after trastuzumab-based treatment.

PURPOSE: To determine the genetic and immune features associated with the recurrence of human epidermal growth factor receptor2-positive (HER2 +) breast cancer (BC) after trastuzumab-based treatment. METHODS: A retrospective cohort study of 48 patients who received trastuzumab-based treatment was divided into recurrent and non-recurrent groups according to clinical follow-up. Baseline samples from all 48 patients were analyzed for genetic variation, HLA allele type, gene expression, and immune features, which were linked to HER2 + BC recurrence. Statistics included logistic regression models, Kaplan-Meier plots, and Univariate Cox proportional hazards models. RESULTS: Compared with the non-recurrent group, the extracellular matrix-related pathway and 3 Hallmark gene sets were enriched in the recurrent group. The infiltration levels of immature B cells and activated B cells were significantly increased in the non-recurrent group, which correlated remarkably with improved overall survival (OS) in two other published gene expression datasets, including TCGA and METABRIC. In the TCGA cohort (n = 275), activated B cells (HR 0.23, 95%CI 0.13-0.43, p < 0.0001), and immature B cells (HR 0.26, 95%CI 0.12-0.59, p < 0.0001). In the METABRIC cohort (n = 236), activated B cells (HR 0.60, 95%CI 0.43-0.83, p = 0.002), and immature B cells (HR 0.65, 95%CI 0.47-0.91, p = 0.011). Cox regression suggested that immature B cells and activated B cells were protective factors for outcome OS. CONCLUSIONS: Aberrant activation of multiple pathways and low baseline tumor-infiltrating B cells are related to HER2 + BC trastuzumab-based recurrence, which primarily affects the antitumor activity of trastuzumab.

Detection of multiple types of cancer driver mutations using targeted RNA sequencing in non-small cell lung cancer.

BACKGROUND: DNA-based next-generation sequencing has been widely used in the selection of target therapies for patients with nonsmall cell lung cancer (NSCLC). RNA-based next-generation sequencing has been proven to be valuable in detecting fusion and exon-skipping mutations and is recommended by National Comprehensive Cancer Network guidelines for these mutation types. METHODS: The authors developed an RNA-based hybridization panel targeting actionable driver oncogenes in solid tumors. Experimental and bioinformatics pipelines were optimized for the detection of fusions, single-nucleotide variants (SNVs), and insertion/deletion (indels). In total, 1253 formalin-fixed, paraffin-embedded samples from patients with NSCLC were analyzed by DNA and RNA panel sequencing in parallel to assess the performance of the RNA panel in detecting multiple types of mutations. RESULTS: In analytical validation, the RNA panel achieved a limit of detection of 1.45-3.15 copies per nanogram for SNVs and 0.21-6.48 copies per nanogram for fusions. In 1253 formalin-fixed, paraffin-embedded NSCLC samples, the RNA panel identified a total of 124 fusion events and 26 MET exon 14-skipping events, in which 14 fusions and six MET exon 14-skipping mutations were missed by DNA panel sequencing. By using the DNA panel as the reference, the positive percent agreement and the positive predictive value of the RNA panel were 98.08% and 98.62%, respectively, for detecting targetable SNVs and 98.15% and 99.38%, respectively, for detecting targetable indels. CONCLUSIONS: Parallel DNA and RNA sequencing analyses demonstrated the accuracy and robustness of the RNA sequencing panel in detecting multiple types of clinically actionable mutations. The simplified experimental workflow and low sample consumption will make RNA panel sequencing a potentially effective method in clinical testing.

Light-Driven Self-Recruitment of Biomimetic Semiconducting Polymer Nanoparticles for Precise Tumor Vascular Disruption.

Tumor vascular disrupting therapy has offered promising opportunities to treat cancer in clinical practice, whereas the overall therapeutic efficacy is notably limited due to the off-target effects and repeated dose toxicity of vascular disrupting agents (VDAs). To tackle this problem, a VDA-free biomimetic semiconducting polymer nanoparticle (SPNP ) is herein reported for precise tumor vascular disruption through two-stage light manipulation. SPNP consists of a semiconducting polymer nanoparticle as the photothermal agent camouflaged with platelet membranes that specifically target disrupted vasculature. Upon the first photoirradiation, SPNP administered in vivo generates mild hyperthermia to trigger tumor vascular hemorrhage, which activates the coagulation cascade and recruits more SPNP to injured blood vessels. Such enhanced tumor vascular targeting of photothermal agents enables intense hyperthermia to destroy the tumor vasculature during the second photoirradiation, leading to complete tumor eradication and efficient metastasis inhibition. Intriguingly, the mechanism study reveals that this vascular disruption strategy alleviates splenomegaly and reverses the immunosuppressive tumor microenvironment by reducing myeloid-derived suppressor cells. Therefore, this study not only illustrates a light-driven self-recruitment strategy to enhance tumor vascular disruption via a single dose of biomimetic therapeutics but also deciphers the immunotherapeutic role of vascular disruption therapy that is conducive to clinical studies.

Deciphering the molecular mechanism of the THBS1 gene in the TNF signaling axis in glioma stem cells.

Glioma stem cells (GSCs) are thought to be responsible for the initiation and progression of glioblastoma (GBM). GBM presents highly invasive growth with a very high recurrence rate, so it has become a clinical problem to be solved urgently. RNAseq demonstrates that thrombospondin 1 (THBS1) acts not only in the angiogenic core of glioma but also with a high degree of invasiveness and infiltration. Nevertheless, defects in the signaling pathway research lead to a poor prognosis in glioma patients. To investigate the relevant molecular mechanism and signal pathway of glioma stem cell behavior mediated by THBS1, U251 astroglioma cells and GSCs were taken as model cells for in vitro experiments. The biological effects of THBS1 on glioma proliferation, migration, and adhesion were evaluated using Cell Counting Kit-8(CCK8) assays, EdU incorporation assays, migration assays, Transwell assays, Western blotting, and RNAseq. We found that the knockout of the THBS1 gene by CRISPR/Cas9 promoted proliferation and migration in U251 cells and GSCs, as well as influencing cell cycle progression by regulating the TNF/MAPK/NF-κB and TGF-ß/Smad signaling pathways. Moreover, U251 cells and GSCs showed different responses to THBS1 knockout, suggesting specific and potential targets for GSCs in signaling pathways mediated by THBS1.

Optimal treatment options for uterine submucosal fibroids: Percutaneous microwave ablation versus transcervical resection of myoma.

OBJECTIVES: To compare the efficacy and safety of percutaneous microwave ablation (PMWA) and transcervical resection of myoma (TCRM) for submucosal fibroids. METHODS: From January 2019 to January 2021, we conducted a randomized controlled study involving patients with symptomatic uterine submucosal fibroids. Questionnaires were also used to measure the uterine fibroid symptom (UFS) scores and quality of life (QoL) scores before and after treatment at 3, 6, and 12 months. Outcomes, adverse events, hemoglobin recovery, and submucosal fibroid volume of both groups were also compared. Operation time, amount of bleeding, hospital stay time, and occurrence of complications were compared in groups with fibroids of different lengths. RESULTS: Follow-up after surgery showed that UFS scores at 3, 6, and 12 months were significantly lower in each group, while QoL scores increased significantly. For fibroids less than 3 cm, surgical time was 34.2 ± 9.9 min, incidence of perioperative complications was 4.2%, and both decreased significantly, compared to the surgical time of the PMWA group (40.0 ± 8.1 min) and incidence of perioperative complications (24%; p < .05 for both). For uterine submucosal fibroids >5 cm, the operation time in the PMWA group was 92.7 ± 16.0 min, intraoperative bleeding volume was 22.7 ± 6.4 mL, and hospital stay was 2.7 ± 1.1 days, which were significantly less than the procedural time (107 ± 11.9 min), intraoperative bleeding loss (45.9 ± 12.8 mL), and length of hospital stay (5.0 ± 1.1 days) in the TCRM group. The differences were statistically significant (p < .05). CONCLUSIONS: PMWA and TCRM were both effective treatments for uterine submucosal fibroids. For fibroids shorter than 3 cm in length, especially pedicled submucosal fibroids, TCRM has absolute advantages; however, for uterine submucosal fibroids >5 cm, PMWA avoids perioperative complications, such as uterine perforation, water poisoning syndrome, and the need for repeat surgery, and is considered the preferred mode of treatment. Therefore, personalized treatment should be used for different patients with uterine submucosal fibroids.

Structural and functional characterization of novel F7 mutations identified in Chinese factor VII-deficient patients.

Hereditary factor VII (FVII) deficiency is a rare recessive bleeding disorder with an estimated prevalence of 1/500 000. We had investigated 50 unrelated Chinese patients with FVII deficiency and identified, in total, 25 mutations, including 18 missense mutations and 5 splicing mutations, on the F7 gene. The nucleotide transition c.1224T>G (p.His408Gln) in exon 9 constitutes a hotspot of mutation, with 19 patients harbouring this genetic variance. Few patients were homozygous or compound heterozygous for deleterious mutations, such as non-sense mutations, large insertion or deletions, indicating that complete deficiency of FVII may not be compatible with life. The eight novel mutations identified in the study, including one small deletion (p.Glu49GlyfsTer101), three type I missense mutations, p.Cys238Phe, p.Gly420Asp, p.Ala252Val and four type II missense mutations, p.Val336Met, p.Ser342Gly, p.Gly432Ser and p.Ile213Asn, were further analysed by in vitro expression and functional studies. The laboratory phenotype and structural analysis confirmed the functional consequence of p.Ile213Asn mutation involving cleavage and activation site. The molecular dynamic simulations and binding energy calculations along with functional probing of p.Gly432Ser mutation revealed the critical role of residue Gly432 in the binding between activated factor VII (factor VIIa) and tissue factor.

Advanced Biomaterials with Intrinsic Immunomodulation Effects for Cancer Immunotherapy.

In recent years, tumor immunotherapy has achieved significant success in tumor treatment based on immune checkpoint blockers and chimeric antigen receptor T-cell therapy. However, about 70-80% of patients with solid tumors do not respond to immunotherapy due to immune evasion. Recent studies found that some biomaterials have intrinsic immunoregulatory effects, except serve as carriers for immunoregulatory drugs. Moreover, these biomaterials have additional advantages such as easy functionalization, modification, and customization. In this review, the recent advances of these immunoregulatory biomaterials in cancer immunotherapy and their interaction with cancer cells, immune cells, and the immunosuppressive tumor microenvironment are summarized. Finally, the opportunities and challenges of immunoregulatory biomaterials used in the clinic and the prospect of their future in cancer immunotherapy are discussed.

Subtype-DCC: decoupled contrastive clustering method for cancer subtype identification based on multi-omics data.

Due to the high heterogeneity and complexity of cancers, patients with different cancer subtypes often have distinct groups of genomic and clinical characteristics. Therefore, the discovery and identification of cancer subtypes are crucial to cancer diagnosis, prognosis and treatment. Recent technological advances have accelerated the increasing availability of multi-omics data for cancer subtyping. To take advantage of the complementary information from multi-omics data, it is necessary to develop computational models that can represent and integrate different layers of data into a single framework. Here, we propose a decoupled contrastive clustering method (Subtype-DCC) based on multi-omics data integration for clustering to identify cancer subtypes. The idea of contrastive learning is introduced into deep clustering based on deep neural networks to learn clustering-friendly representations. Experimental results demonstrate the superior performance of the proposed Subtype-DCC model in identifying cancer subtypes over the currently available state-of-the-art clustering methods. The strength of Subtype-DCC is also supported by the survival and clinical analysis.

MDDI-SCL: predicting multi-type drug-drug interactions via supervised contrastive learning.

The joint use of multiple drugs may cause unintended drug-drug interactions (DDIs) and result in adverse consequence to the patients. Accurate identification of DDI types can not only provide hints to avoid these accidental events, but also elaborate the underlying mechanisms by how DDIs occur. Several computational methods have been proposed for multi-type DDI prediction, but room remains for improvement in prediction performance. In this study, we propose a supervised contrastive learning based method, MDDI-SCL, implemented by three-level loss functions, to predict multi-type DDIs. MDDI-SCL is mainly composed of three modules: drug feature encoder and mean squared error loss module, drug latent feature fusion and supervised contrastive loss module, multi-type DDI prediction and classification loss module. The drug feature encoder and mean squared error loss module uses self-attention mechanism and autoencoder to learn drug-level latent features. The drug latent feature fusion and supervised contrastive loss module uses multi-scale feature fusion to learn drug pair-level latent features. The prediction and classification loss module predicts DDI types of each drug pair. We evaluate MDDI-SCL on three different tasks of two datasets. Experimental results demonstrate that MDDI-SCL achieves better or comparable performance as the state-of-the-art methods. Furthermore, the effectiveness of supervised contrastive learning is validated by ablation experiment, and the feasibility of MDDI-SCL is supported by case studies. The source codes are available at https://github.com/ShenggengLin/MDDI-SCL .

Dendritic lipopeptide liposomes decorated with dual-targeted proteins.

Due to their homing effects, cell and cell membrane-derived nanocarriers have been widely used to enhance drug target delivery. Inspired by the protein-anchored cell membrane architecture, we here report a tumor-targeted liposome, dtDLP, which was constructed through the electrostatic interaction between dendritic lipopeptide liposomes and a dual-targeted recombinant protein, achieving superior tumor homing, cellular endocytotic and penetration abilities. The dual-targeted recombinant protein consists of an anti-epidermal growth factor receptor single domain antibody and a peptide ligand for the integrin αvß3. dtDLPs substantially reduced macrophage phagocytosis and increased drug internalization in both 4T1 cells and HeLa cells by providing more endocytic pathways. In addition, the dtDLPs showed great penetration ability in both multicellular spheroids and tumor tissues. Due to the improved cancer cellular uptake and tumor penetration, the dtDLPs exhibited a superior anticancer effect in both HeLa and 4T1 tumor-bearing mice. This work will be helpful for the design of cell-specific liposomes with admirable tumor targeting, endocytotic and penetration abilities.

Medium Activity Prevents Periprosthetic Bone Mass Loss in the Medial Metaphyseal Region of the Tibia after Posterior-Stabilized TKA: A 5-Year Follow-up Study of 110 Knees.

OBJECTIVE: The bone mass around the prosthesis plays an important role in the stability of the prosthesis. This study aimed to assess the effect of postoperative activity on bone mineral density (BMD) in the proximal tibia 5 years after total knee arthroplasty (TKA). To provide a scientific guidance for postoperative functional exercise. METHODS: 110 patients underwent unilateral primary TKA were divided into three groups based on the University of California Los Angeles (UCLA) activity scale: low activity group (LA group, UCLA = 4, 5); medium activity group (MA group, UCLA = 6, 7); and high activity group (HA group, UCLA = 8, 9). The primary observation was a comparison of the BMD and BMD change percentage (ΔBMD (%)) in the periprosthetic tibia among the LA, MA and HA groups at 1 year, 3 years and 5 years. The secondary observations were radiographic evaluation (prosthetic stability, periprosthetic fractures, aseptic loosening and periprosthetic joint infection) and clinical evaluation (Knee Society Score (KSS), visual analogue score scores and range of motion (ROM)). A one-way ANOVA was used to compare the clinical scores and BMD among the three groups. RESULTS: The BMD of medial region decreased by 10.80%, 12.64%, 13.61% at 1, 3, and 5 years respectively; these were 5.72%, 6.26%, 7.83% in lateral region and 1.42%, 1.78%, 3.28% in diaphyseal region. For medial metaphyseal region, the BMD of the MA group was significantly greater than that of the LA and HA groups at 1 and 3 years (108.9 ± 5.2 vs. 106.1 ± 6.69 vs. 105.4 ± 5.2 and 108.5 ± 6.0 vs. 101.2 ± 6.76 vs. 103.0 ± 6.8, P < 0.01 and P < 0.001), and the BMD changes (ΔBMD (%)) in the MA group were significantly smaller than those in the LA and HA groups (8.75 ± 5.36 vs. 11.92 ± 5.49 vs. 12.70 ± 5.21 and 9.11 ± 5.11 vs. 16.04 ± 4.79 vs. 14.82 ± 4.26, P < 0.01 and P < 0.001). Regarding secondary observations, all of the prostheses were assessed as stable, without periprosthetic fractures, aseptic loosening and periprosthetic joint infection. Regarding KSS scores, there was no significant difference among the three groups. However, the VAS and ROM of the HA group were better than those of the MA and LA groups (1.65 ± 0.79 vs. 2.63 ± 0.77 vs. 3.00 ± 1.17, p < 0.001, and 111.90 ± 9.17 vs. 110.20 ± 6.78 vs. 102.90 ± 8.48, P < 0.001). CONCLUSION: Medium activity prevented periprosthetic bone loss in the medial metaphyseal region of the tibia after posterior-stabilized TKA, and moderate-intensity exercise is recommended for patients after TKA to reduce periprosthetic bone loss.