Deubiquitinase USP9X stabilizes RNA m6A demethylase ALKBH5 and promotes acute myeloid leukemia cell survival.

Post-translational modifications including protein ubiquitination regulate a plethora of cellular processes in distinct manners. RNA N6-methyladenosine is the most abundant post-transcriptional modification on mammalian mRNAs and plays important roles in various physiological and pathological conditions including hematologic malignancies. We previously determined that the RNA N6-methyladenosine eraser ALKBH5 is necessary for the maintenance of acute myeloid leukemia (AML) stem cell function, but the post-translational modifications involved in ALKBH5 regulation remain elusive. Here, we show that deubiquitinase ubiquitin-specific peptidase 9X (USP9X) stabilizes ALKBH5 and promotes AML cell survival. Through the use of mass spectrometry as an unbiased approach, we identify USP9X and confirm that it directly binds to ALKBH5. USP9X stabilizes ALKBH5 by removing the K48-linked polyubiquitin chain at K57. Using human myeloid leukemia cells and a murine AML model, we find that genetic knockdown or pharmaceutical inhibition of USP9X inhibits leukemia cell proliferation, induces apoptosis, and delays AML development. Ectopic expression of ALKBH5 partially mediates the function of USP9X in AML. Overall, this study uncovers deubiquitinase USP9X as a key for stabilizing ALKBH5 expression and reveals the important role of USP9X in AML, which provides a promising therapeutic strategy for AML treatment in the clinic.

Psychometric Properties of the Brief Pain Inventory Among Patients With Osteoarthritis Undergoing Total Knee Arthroplasty Surgery.

BACKGROUND: Knee osteoarthritis (OA) is characterized by pain and functional restrictions, necessitating precise and reliable pain evaluation for effective disease surveillance and postoperative treatment appraisal. METHODS: This investigation recruited 110 participants who were slated to receive unilateral total knee arthroplasty (TKA) and administered 3 self-reported questionnaires: the Brief Pain Inventory (BPI), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 5-level EuroQoL Group's 5-dimension questionnaire (EQ-5D-5L), at baseline and 1 year after surgery. Using standard statistical methods and indicators, the BPI was subjected to a battery of psychometric evaluations, including assessments of reliability, validity, and responsiveness. RESULTS: At baseline, there were no significant ceiling or floor effects observed. Additionally, the internal consistency reliability (Cronbach's alpha) of the BPI was above 0.8, suggesting that the questionnaire items are adequately related to one another. The study found moderate to very strong correlations between the pain and physical function domains of the BPI and Western Ontario and McMaster Universities Osteoarthritis Index, as well as a strong correlation between the functional interference dimension of the BPI and the EQ-5D, supporting the construct validity of the BPI. Also, the BPI was found to be responsive to changes in pain over time, with a responsiveness index ranging from 2.55 to 3.19. CONCLUSION: The BPI assessment tool demonstrated good reliability, validity, and responsiveness in knee osteoarthritis patients who have undergone TKA and can be a useful measurement tool in clinical research to evaluate the effectiveness of pain management strategies and surgical interventions.

Nuclear receptor coactivator 3 transactivates proinflammatory cytokines in collagen-induced arthritis.

Rheumatoid arthritis (RA) is an autoimmune disorder in which the immune system mistakenly attacks joints. The molecular mechanisms underlying RA pathology are still under investigation. In this study, we discovered overexpression of nuclear receptor coactivator 3 (NCOA3) in the joint tissues of type II collagen-induced arthritis (CIA) mice, an important autoimmune model of human RA. Administration of two NCOA3 inhibitors, gossypol (GSP) and SI-2 hydrochloride (SHC), significantly alleviated inflammation and improved the outcomes of CIA mice. In vivo and in vitro experiments revealed that NCOA3 assembled a transcriptional complex with a histone acetyltransferase p300 and two subunits of nuclear factor kappa B (NF-κB). This complex specifically controlled the expression of proinflammatory cytokine genes by binding to their promoters. Knockdown of NCOA3 or in vitro treatments with GSP and SHC impaired the assembly of NCOA3-p300-NF-κB complex and decreased the expression of proinflammatory cytokine genes. Taken together, our results demonstrated that NCOA3 acts as a mediator of proinflammatory cytokine genes in CIA mice and that inhibition of the NCOA3-p300-NF-κB complex may represent a new avenue for improving RA outcomes.

Plantar Pressure Distribution and Posture Balance During Walking in Individuals with Unilateral Chronic Ankle Instability: An Observational Study.

BACKGROUND Patients with chronic ankle instability (CAI) can present with abnormal gait. The purpose of this study was to evaluate plantar pressure distributions and posture balance during walking in unilateral CAI patients. MATERIAL AND METHODS We recruited 24 unilateral CAI patients and 24 healthy individuals; plantar pressure analysis was conducted using the Footscan® 3D pressure system. The following parameters were assessed and recorded: peak force/weight (PF/W), time to peak force (TPF), time to boundary (TTB), and COP velocity. The differences between the affected and unaffected side of the CAI group and control group were determined. Pearson correlation analysis and univariate analysis was used to investigate the correlation between plantar pressure parameters and related factors. RESULTS The comparison of PF/W showed that the plantar pressure of both sides in the CAI group were laterally distributed. The comparison of TPF, TTB, and COP velocity in different groups showed that the posture balance on the affected side of CAI patient was more impaired than the unaffected side and the control group. Male patients with CAI tend to have better posture balance than females, and a low CAIT score is correlated with poor posture balance. CONCLUSIONS The plantar pressure on both sides in unilateral CAI patients was laterally distributed and their balance function was impaired. It is necessary for CAI patients to receive functional training of both sides during rehabilitation, and plantar pressure analysis is promising for diagnosis and evaluation of CAI.

Evaluation of relationship between KEAP1 gene and genetic susceptibility of deep vein thrombosis after orthopedic surgery in Han Chinese population.

Deep vein thrombosis (DVT) is the blood clot formed in a vein deep in body, mostly occurred in the lower leg or thigh. Early studies indicate that DVT is a complex disorder affected by both environmental and genetic factors. Previous biological evidence have indicated that KEAP1 gene may play an important role in the pathogenesis of DVT. In the present study, we aimed to investigate the genetic association between genetic polymorphisms of KEAP1 gene and the risk of DVT in Han Chinese population. A total of 2558 study subjects comprised of 660 DVT following orthopedics surgery cases and 1898 controls were recruited as discovery sample. In addition, we have also recruited another independent sample sets including 704 DVT following orthopedics surgery cases and 1056 controls for replication. Ten tag SNPs located on KEAP1 gene were selected for genotyping. Single marker based association analyses were conducted at both allelic and genotypic levels. SNPs that passed the Bonferroni correction in the discovery stage were genotyped in the replication dataset. Bioinformatics tools including PolymiRTS, GTEx, STRING and Gene Ontology database were utilized to investigate the functional consequences of the significant SNPs. SNP rs3177696 was identified to be significantly associated with risk of DVT in the study subjects. The G allele of SNP rs3177696 was significantly related to decreased risk of DVT. Functional consequences of SNP rs3177696 were obtained based on bioinformatics analyses. The G allele of SNP rs3177696 was related to the increased gene expression level of KEAP1. In summary, we have identified KEAP1 gene to be a potential susceptible locus for DVT in Han Chinese population. Further bioinformatics analyses have provided supportive evidence for the functional consequence of the significant SNP.

Identification of Novel Target for Osteosarcoma by Network Analysis.

BACKGROUND Osteosarcoma (OS) is a highly complicated bone cancer involving imbalance of signaling transduction networks in cells. Development of new anti-osteosarcoma drugs is very challenging, mainly due to lack of known key targets. MATERIAL AND METHODS In this study, we attempted to reveal more promising targets for drug design by "Target-Pathway" network analysis, providing the new therapeutic strategy of osteosarcoma. The potential targets used for the treatment of OS were selected from 4 different sources: DrugBank, TCRD database, dbDEMC database, and recent scientific literature papers. Cytoscape was used for the establishment of the "Target-Pathway" network. RESULTS The obtained results suggest that tankyrase 2 (TNKS2) might be a very good potential protein target for the treatment of osteosarcoma. An in vitro MTT assay proved that it is an available option against OS by targeting the TNKS2 protein. Subsequently, cell cycle and apoptosis assay by flow cytometry showed the TNKS2 inhibitor can obviously induce cell cycle arrest, apoptosis, and mitotic cell death. CONCLUSIONS Tankyrase 2 (TNKS2), a member of the multifunctional poly(ADP-ribose) polymerases (PARPs), could be a very useful protein target for the treatment of osteosarcoma.

Bibliometric and visual analysis of research on analgesia and total knee arthroplasty from 1990 to 2022.

Background: In recent decades, there have been notable advancements in the field of analgesia and total knee arthroplasty (TKA). This study aims to employ bibliometric analysis to elucidate the prevailing research focal points and trends within analgesia and TKA from 1990 to 2022. Material and methods: Relevant publications were retrieved from the Web of Science Core Collection. CiteSpace, VOSviewer, and Scimago Graphica were used for visualization and bibliometric analysis of countries, institutions, authors, journals, references, and keywords. Results: A total of 2776 publications on analgesia and TKA were identified, with the United States having the highest number of publications. The University of Copenhagen was the most productive institution, and Kehlet, Henrik was the most prolific author. The Journal of Arthroplasty had the most publications and citations. The most common keywords were "TKA," "pain management," "postoperative pain," "Total hip arthroplasty (THA)," and "postoperative management." Keyword burst detection demonstrated that adductor canal block (ACB) was a recent research hotspot. Conclusion: Our study revealed a sharp increase in global publications on analgesia and TKA, and this trend is expected to continue. Further research is necessary to determine the optimal regimen for multimodal analgesia, the ideal location and volume of ACB, and their clinical significance.

Translation, Cross-Cultural Adaptation and Validation of the Chinese Version of the High Activity Arthroplasty Score.

Background: The High Activity Arthroplasty Score (HAAS) is a validated score that assesses functional outcomes after lower limb arthroplasty, with fewer ceiling effects than other scores. The aim is to translate and cross-culturally adapt the HAAS into a Chinese version (HAAS-C) and to evaluate the psychometric properties of HAAS-C in patients after primary total knee arthroplasty (TKA). Methods: A total of 104 patients diagnosed with knee osteoarthritis who had undergone TKA at least 12 months prior were recruited. A forward and backward translation procedure was performed for developing a culturally acceptable HAAS-C. Internal consistency was assessed using Cronbach's α, and test-retest reliability was measured using the intraclass correlation coefficient (ICC) within a 10-day interval. Construct validity was assessed by examining the correlations between HAAS-C and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQoL Group's five-dimension questionnaire (EQ-5D-5L), and Oxford knee score (OKS). Results: HAAS-C demonstrated adequate Internal consistency reliability, as indicated by Cronbach's α coefficient of 0.75. Test-retest reliability yielded excellent results, with an ICC value of 0.98. Content validity indices were high, with a scale-level validity index of 0.9 and item-level validity indices greater than or equal to 0.8. HAAS-C showed a strong correlation with WOMAC (r = 0.69), a moderate correlation with EQ-5D-5L (r = 0.43), and OKS (r = 0.53) while exhibiting no floor or ceiling effects. Conclusion: The validated HAAS-C questionnaire is a valid instrument for assessing patients undergoing TKA in mainland China.

Reprogramming of RNA m6A Modification Is Required for Acute Myeloid Leukemia Development.

Hematopoietic homeostasis is maintained by hematopoietic stem cells (HSCs), and it is tightly controlled at multiple levels to sustain the self-renewal capacity and differentiation potential of HSCs. Dysregulation of self-renewal and differentiation of HSCs leads to the development of hematologic diseases, including acute myeloid leukemia (AML). Thus, understanding the underlying mechanisms of HSC maintenance and the development of hematologic malignancies is one of the fundamental scientific endeavors in stem cell biology. N  6-methyladenosine (m6A) is a common modification in mammalian messenger RNAs (mRNAs) and plays important roles in various biological processes. In this study, we performed a comparative analysis of the dynamics of the RNA m6A methylome of hematopoietic stem and progenitor cells (HSPCs) and leukemia-initiating cells (LICs) in AML. We found that RNA m6A modification regulates the transformation of long-term HSCs into short-term HSCs and determines the lineage commitment of HSCs. Interestingly, m6A modification leads to reprogramming that promotes cellular transformation during AML development, and LIC-specific m6A targets are recognized by different m6A readers. Moreover, the very long chain fatty acid transporter ATP-binding cassette subfamily D member 2 (ABCD2) is a key factor that promotes AML development, and deletion of ABCD2 damages clonogenic ability, inhibits proliferation, and promotes apoptosis of human leukemia cells. This study provides a comprehensive understanding of the role of m6A in regulating cell state transition in normal hematopoiesis and leukemogenesis, and identifies ABCD2 as a key factor in AML development.

Five-Factor Personality Dimensions Mediated the Relationship between Parents' Parenting Style Differences and Mental Health among Medical University Students.

BACKGROUND: Previous studies have identified the relationships between parental parenting style, personality, and mental health. However, the interactive influences between mother's and father's parenting styles on personality have been examined less often. To fill the gaps, the first aim of this study was to build the relationships between parental parenting style differences (PDs) and five-factor personality dimensions. The second aim was to test the mediating effect of five-factor personality dimensions on the relationships between parental parenting style differences and mental health. METHODS: This is a cross-sectional study conducted among medical university students, and 2583 valid participants were analyzed. Mental health was measured by the Kessler-10 scale. The Chinese Big Five Personality Inventory brief version (CBF-PI-B) was used to access five-factor personality dimensions. PD was calculated by the short form of Egna Minnen av Barndoms Uppfostran. Linear regressions were conducted to analyze the associations between PD and five-factor personality dimensions. The SPSS macros program (PROCESS v3.3) was performed to test the mediating effect of five-factor personality dimensions on the associations between PD and mental health. RESULTS: Linear regressions found that worse mental health was positively associated with PD (ß = 0.15, p < 0.001), higher neuroticism (ß = 0.61, p < 0.001), lower conscientiousness (ß = -0.11, p < 0.001), lower agreeableness (ß = -0.10, p < 0.01), and lower openness (ß = -0.05, p < 0.05). The results also supported that PD was positively associated with lower conscientiousness (ß = -0.15, p < 0.01), lower agreeableness (ß = -0.09, p < 0.001), lower openness (ß = -0.15, p < 0.001), and lower extraversion (ß = -0.08, p < 0.001), respectively. The mediating effect of agreeableness or openness was supported for the relationships between PD and mental health. CONCLUSION: These findings remind us of the importance of consistent parenting styles between mother and father, and they also can be translated into practices to improve mental health among medical university students.

Consequences of using poly-ether-ether-ketone versus traditional implant on tibial cement penetration and short-term clinical outcomes during total knee arthroplasty: a randomized controlled trial.

BACKGROUND: The use of poly-ether-ether-ketone (PEEK) prosthesis during total knee arthroplasty (TKA) is a relatively new concept. Several studies have suggested that the thickness of cement penetration during TKA may affect the stability of the implants. The present study aimed to compare the cement penetration and clinical performance between PEEK and traditional cobalt chromium molybdenum (CoCrMo) prosthesis during TKA. METHODS: This study was a randomized controlled trial with level I of evidence. A total of 48 patients were randomly assigned to either the PEEK group (n = 24) or the CoCrMo group (n = 24). Mean bone cement penetration under the tibial baseplate was assessed radiographically in four zones in the anteroposterior view and two zones in the lateral view, in accordance with the Knee Society Scoring System. Furthermore, parameters such as the Knee Society Score (KSS), visual analogue scale (VAS) scores, complications and survivorship at 1 year postoperatively were also compared. RESULTS: According to the results of this study, the mean bone cement penetration exhibited no significant difference between PEEK and CoCrMo groups (2.49 ± 0.61 mm vs. 2.53 ± 0.68 mm, p = 0.85). Additionally, there were no remarkable differences in the KSS clinical score, functional score, and VAS score between the two groups. Moreover, complications and survivorship were also statistically compared between the groups and presented no significant differences. CONCLUSIONS: Based on the current findings, it can be concluded that PEEK implant present similar bone cement penetration, short-term clinical outcomes, and survivorship with traditional CoCrMo implant in TKA without added complications. Trial registration Chinese Clinical Trial Registry (ChiCTR2100047563).

Cost, time savings and effectiveness of wearable devices for remote monitoring of patient rehabilitation after total knee arthroplasty: study protocol for a randomized controlled trial.

BACKGROUND: Total knee arthroplasty (TKA) is a surgical procedure primarily used to treat patients with end-stage knee osteoarthritis (KOA). Postoperative physical exercise is a critical part of the overall treatment of KOA and can bring significant benefits to the patients' recovery. Wearable devices can monitor patients' exercise data and upload it to the physician's workstation. This allows the rehabilitation physician to make timely adjustments based on the patients' movement feedback, and the surgeon can be informed of the patients' functional status. Overall, this study aims to evaluate the effectiveness of using wearable monitoring devices for rehabilitation exercise after TKA, with a focus on cost, time savings, and patient outcomes. METHOD/DESIGN: This is a single-center, single-blinded, parallel randomized controlled trial conducted at Xi'an Honghui Hospital, a regional orthopedic medical center. Eligible patients will be recruited to participate in the study, and baseline data collection and clinical assessments will be conducted at the time of admission. Using the principle of random allocation, recruited patients will be divided into either the experimental or control group. Both groups will undergo a standard, widely promoted rehabilitation program. The patients in the experimental group will wear equipment to detect and track mobility in the lower limbs. All patients will return to the outpatient clinic for follow-up assessments at 2 weeks, 12 weeks, and 24 weeks after discharge, where outcome indicators will be measured. The primary outcome will be the cost and time after discharge, while secondary outcomes will include the 6-min walk test (6MWT), range of motion (ROM), visual analog scale (VAS), American Knee Society Score (KSS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). DISCUSSION: We should encourage the adoption of novel, easy-to-use, supervised devices if they prove to be beneficial for patients in terms of cost, time, and effectiveness after TKA. This type of device is particularly important for people in remote rural areas, those with limited financial resources, and those who are reluctant to return to hospitals for follow-up care. Trial registration Chinese Clinical Trial Registry ChiCTR2300068418. Registered on 17 February 2023.

Cross-cultural adaptation and validation for central sensitization inventory: based on Chinese patients undergoing total knee arthroplasty for knee osteoarthritis.

BACKGROUND: This study was conducted to develop a simplified Chinese version of the central sensitization inventory (CSI-CV) and to evaluate its reliability and validity. METHODS: The CSI-CV was developed through a process involving the translation and back translation of the original CSI. Subsequently, experts reviewed and revised the content of the items to ensure their appropriateness. A total of 325 patients with knee osteoarthritis (KOA), who were scheduled to undergo total knee arthroplasty (TKA), completed the CSI-CV at a prominent orthopedic center in Xi'an, China. Afterward, a random selection of 100 participants was chosen for retesting after one week. The reliability and validity of the inventory were evaluated through exploratory factor analysis, correlation coefficient calculation and other methods. RESULTS: The CSI-CV consists of 25 items in five dimensions (emotional distress, headache and jaw symptoms, physical symptoms, urological symptoms, and fatigue and sleep problems). The cumulative variance contribution rate was 75.3%, the Cronbach's α coefficient was 0.83, the Guttman split-half reliability coefficient was 0.88 and the intraclass correlation coefficient was 0.965. The CSI-CV scores correlated moderately with the total scores of the brief pain inventory (r = 0.506), Western Ontario and McMaster Universities Osteoarthritis Index (r = 0.466) and EuroQoL Group's five-dimension questionnaire (r = 0.576). CONCLUSIONS: The findings demonstrate that the CSI was successfully trans-culturally adapted into a simplified Chinese version (CSI-CV) that was reliable and valid for Chinese-speaking patients who awaiting TKA for KOA.

Validation of the Chinese version of the Brief Pain Inventory in patients with knee osteoarthritis.

BACKGROUND: Knee osteoarthritis (KOA) primarily presents with symptoms of pain and compromised functionality. Pain is a subjective manifestation that necessitates the employment of reliable evaluation tools for practical assessment, thereby enabling the formulation of appropriate interventional strategies. The Brief Pain Inventory (BPI) is a widely utilized questionnaire for evaluating the status of chronic pain. The purpose of the present study is to translate the short form of BPI into Chinese version (BPI-CV) and conduct cross-cultural adaptation to evaluate the psychometric characteristics of BPI-CV in KOA patients. METHODS: BPI-CV was translated and cross-culturally adapted according to internationally recognized guidelines. A cohort comprising 150 patients diagnosed with KOA successfully completed the demographic questionnaire, BPI-CV, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the EuroQoL Group's five-dimension questionnaire (EQ-5D). Internal consistency and test-retest analysis were used to evaluate the reliability. The internal consistency of the scale items was evaluated by calculating the Cronbach's α value (> 0.7). We chose to employ two scales commonly used in the evaluation of KOA patients: the disease-specific WOMAC scale and the universal EQ-5D scale. Construct validity was determined through Pearson correlation analysis, comparing BPI scores with those obtained from the WOMAC and EQ-5D scales. Exploratory factor analysis was used to structural validity. RESULTS: The BPI-CV was well accepted with no ceiling or floor effect. Cronbach's α for assessing internal consistency was 0.894. Test-retest reliability was excellent with an ICC of 0.852 (95%CI 0.785-0.905). The BPI-CV showed moderate to strong correlations with the pain dimension (r = 0.496-0.860) and the functional interference dimension (r = 0.517-0.712) of the WOMAC and the EQ-5D (r = 0.527-0.743). Three factors resulted using exploratory factor analysis: pain severity, activity interference, and emotional interference, accounting for 79.0% of the total variance. Standard error of measurement was 0.539. CONCLUSION: BPI-CV has good feasibility, reliability, and validity. It can be recommended for KOA patients in mainland China.

Translation and validation of the Chinese version of the Japan Frailty Scale.

Purpose: Frailty is a difficult-to-measure condition that is susceptible to adverse outcomes. The Japan Frailty Scale (JFS) is a tool for assessing frailty status in older adults. This study aimed to translate and culturally adapt the JFS into a Chinese version (JFS-C). Materials and methods: The study included 160 older adults as participants. Internal consistency was assessed using Cronbach's alpha, and test-retest reliability was conducted using the intraclass correlation coefficient (ICC). Convergent validity was evaluated by assessing the correlation between JFS-C and the Barthel Index, the Frail scale, and the 36-item Short-Form Health Survey (SF-36). Criterion validity was assessed by comparing JFS-C scores with the Frail scale. Results: JFS-C demonstrated adequate internal consistency (Cronbach's alphas = 0.711) and excellent test-retest reliability over a 7 to 10-day interval (ICC = 0.949). Correlation analysis showed a strong positive correlation between JFS-C and the Frail scale (r = 0.786, p < 0.001), a moderate negative correlation with the Barthel Index (r = -0.598, p < 0.001), and moderate correlations with various subscales of SF-36 (r = -0.574 to -0.661). However, no significant correlations were found between JFS-C and SF-36 mental health (r = -0.363, p < 0.001) or role emotional (r = -0.350, p < 0.001). Based on the reference standard of the Frail scale phenotype (score ≥ 2), the cutoff value for JFS-C was determined to be 3. Conclusion: JFS-C demonstrates good reliability and validity in assessing frailty among the older population in China.

Mapping knowledge landscapes and emerging trends of robotic-assisted knee arthroplasty: A bibliometric analysis.

The robotic-assisted knee arthroplasty has gained increasing attention in the research field. To date, no comprehensive bibliometric analysis has been carried out on this topic. The present study aimed to introduce the research status and hotspots and explore the field of robotic-assisted knee arthroplasty from a bibliometric perspective. The Web of Science Core Collection database was utilized to retrieve articles and reviews on robotic-assisted knee arthroplasty published between 1993 and 2023. CiteSpace, VOSviewer, Scimago Graphica, Pajek, and a bibliometric online analysis platform (http://bibliometric.com/) were employed to analyze the regions, institutions, journals, authors, and keywords, aiming to predict the latest trends in research related to robotic-assisted knee arthroplasty. This study encompasses 697 records. The annual publication count pertaining to robotic-assisted knee arthroplasty demonstrates consistent growth. The United States leads with the highest number of studies (298), trailed by the United Kingdom (110) and France (49). The Hospital for Special Surgery emerges as the most prolific institution, while Professor Mont, Michael A holds significant author influence. The Journal of Arthroplasty reigns supreme in this field, boasting the highest publication and citation figures. Funding sources predominantly include Stryker (34), Smith Nephew (19), and the National Natural Science Foundation of China (17). Noteworthy research themes within robotic-assisted knee arthroplasty encompass patient satisfaction, kinematic alignment, and clinical benefits. The landscape of robotic-assisted knee arthroplasty research is thriving. Anticipated trajectories of research will be geared toward refining the precision of robotic technology and enhancing clinical outcomes within the realm of robotic-assisted knee arthroplasty.

Decoding m6A RNA methylome identifies PRMT6-regulated lipid transport promoting AML stem cell maintenance.

N6-methyladenosine (m6A) is a common chemical modification for mammalian mRNA and exhibits high dynamics in various biological processes. However, dynamics of m6A RNA methylome during leukemogenesis remains unknown. Here, we delineate a comprehensive m6A landscape during acute myeloid leukemia (AML) development and identify PRMT6 as a key for maintaining AML stem cells. We observe an obvious change in m6A methylome during leukemogenesis and find that protein arginine methyltransferase PRMT6 and m6A reader IGF2BP2 maintain the function of human and murine leukemia stem cells (LSCs). Genetic deletion or pharmacological inhibition of PRMT6 damages AML development and LSC function. Mechanistically, IGF2BP2 stabilizes PRMT6 mRNA via m6A-mediated manner, which catalyzes H3R2me2a and suppresses lipid transporter MFSD2A expression. PRMT6 loss upregulates MFSD2A expression that increases docosahexaenoic acid levels and impairs LSC maintenance. Collectively, our findings reveal a critical role of PRMT6-MFSD2A signaling axis in AML development and provide a therapeutic strategy for targeting LSCs.

The optimal angle of screw for using cement-screw technique to repair tibial defect in total knee arthroplasty: a finite element analysis.

BACKGROUND: The cement-screw technique is a convenient method to repair tibial plateau defects in primary and revision total knee arthroplasty (TKA). However, the optimal angle of screw insertions is unknown. This study aimed to perform a finite element analysis (FEA) to determine the optimal screw angle for the repair of tibial plateau defects in TKA. METHODS: Seven FEA models were set and two common different defects (defect 1: area < 12%, depth < 12 mm; defect 2: area > 12%, depth > 12 mm) were simulated. One screw was used in defect 1, and one or two screws were used in defect 2. Screws were parallel to the proximal cortical bone (oblique screw) or perpendicular to the upper surface (vertical screw) of the tibia. Contact stresses on cancellous bone in different areas were determined. Maximum principal stress on the cancellous bone around each screw was also compared. RESULTS: The FEA models showed that stresses on the surface of cancellous bone in tibial defect (0.13-0.39 MPa) and stress focus spot (0.45 MPa) around the screw were lower when one vertical screw was used in defect 1. The stresses on the surface of cancellous bone in tibial defect (0.09-0.44 MPa), stresses in the medial tibial plateau (0.14-0.21 MPa), and stress focus spot around the screws were lowest (0.42 MPa and 1.37 MPa) when two vertical screws were used in defect 2, followed by of one vertical and one oblique (0.16-0.48 MPa; 0.15-0.21 MPa; 1.63 MPa and 1.11 MPa). No other statistically significant differences were found. CONCLUSIONS: Either for one or two screws, those perpendicular to the upper surface achieve better stability than those parallel to the proximal cortical bone of the tibia. If two vertical screws cannot be performed, one vertical and one oblique is also acceptable.

One-Year Prevalence of Perceived Medical Errors or Near Misses and Its Association with Depressive Symptoms among Chinese Medical Professionals: A Propensity Score Matching Analysis.

Objective: Medical errors or near misses (MENM) may cause serious negative outcomes for the patients. However, medical professionals with MENM may also be secondary victims. Although the association between MENM and depression among medical professionals has been explored in several previous studies, the possible causal relationship has been explored less, especially in China. In this study, our first aim was to determine the prevalence of MENM among Chinese medical professionals. We also wanted to explore the causal effect of MENM on depressive symptoms based on a propensity-score matching analysis. Methods: A cross-sectional study was conducted among medical professionals in Chinese public general hospitals, and 3426 medical professionals were analyzed in this study. The Center for Epidemiologic Studies Depression (CES-D) scale was used to assess depressive symptoms. Social support was measured by the Multidimensional Scale of Perceived Social Support (MSPSS). MENM, social-demographic variables, occupational characteristics, and physical disease were also evaluated in this study. Results: The one-year prevalence of perceived MENM was 2.9% among medical professionals in Chinese public general hospitals. The results of logistic regressions showed that working hours/week (OR = 1.02, p < 0.05) and depressive symptoms (OR = 1.05, p < 0.001) were associated with MENM. After propensity score matching, depressive symptoms were associated with MENM (OR = 1.05, p < 0.001) among medical professionals. The associations between occupational characteristics, physical disease, social support, and MENM were not supported by this study. Conclusions: The one-year prevalence of MENM was low in Chinese public general hospitals, and based on our propensity score matching analyses, the occurrence of MENM may cause depressive symptoms in medical professionals. A bigger effort by health systems and organizations may be helpful for reducing MENM.

Epileptic Seizure Detection Based on Bidirectional Gated Recurrent Unit Network.

Visual inspection of long-term electroencephalography (EEG) is a tedious task for physicians in neurology. Based on bidirectional gated recurrent unit (Bi-GRU) neural network, an automatic seizure detection method is proposed in this paper to facilitate the diagnosis and treatment of epilepsy. Firstly, wavelet transforms are applied to EEG recordings for filtering pre-processing. Then the relative energies of signals in several particular frequency bands are calculated and inputted into Bi-GRU network. Afterwards, the outputs of Bi-GRU network are further processed by moving average filtering, threshold comparison and seizure merging to generate the discriminant results that the tested EEG belong to seizure or not. Evaluated on CHB-MIT scalp EEG database, the proposed seizure detection method obtained an average sensitivity of 93.89% and an average specificity of 98.49%. 124 out of 128 seizures were correctly detected and the achieved average false detection rate was 0.31 per hour on 867.14 h testing data. The results show the superiority of Bi-GRU network in seizure detection and the proposed detection method has a promising potential in the monitoring of long-term EEG.