Reversine inhibits proliferation and induces apoptosis of human osteosarcoma cells through targeting MEK1.

Reversine, or 2-(4-morpholinoanilino)-6-cyclohexylaminopurine, is a 2,6-disubstituted purine derivative. This small molecule shows anti-tumor potential by playing a central role in the inhibition of several kinases related to cell cycle regulation and cytokinesis. In this study, systematic review demonstrated the feasibility and pharmacological mechanism of anti-tumor effect of reversine. Firstly, we grafted MNNG/HOS, U-2 OS, MG-63 osteosarcoma cell aggregates onto chicken embryonic chorioallantoic membrane (CAM) to examine the tumor volume of these grafts after reversine treatment. Following culture, reversine inhibited the growth of osteosarcoma cell aggregates on CAM significantly. In vitro experiment, reversine suppressed osteosarcoma cell viability, colony formation, proliferation, and induced apoptosis and cell cycle arrest at G0-G1 phase. Scratch wound assay demonstrated that reversine restrained cell migration. Reversine increased the protein expression of E-cadherin. The mRNA expression of Rac1, RhoA, CDC42, PTK2, PXN, N-cadherin, Vimentin in MNNG/HOS, U-2 OS and MG-63 cells were suppressed and PTEN increased after reversine treatment. Network pharmacology prediction, molecular docking and systematic review revealed MEK1 can be used as an effective target for reversine to inhibit osteosarcoma. Western blot results show the regulation of MEK1 and ERK1/2 by reversine was not consistent in different osteosarcoma cell lines, but we found that reversine significantly inhibited the protein expression of MEK1 in MNNG/HOS, U-2 OS and MG-63. All these suggested that reversine can exert its anti-tumor effect by targeting the expression of MEK1.

Preliminary study of short-term outcomes and learning curves of robotic-assisted THA: comparison between closed platform robotic system and open platform robotic system.

BACKGROUND: Both closed platform and open platform robotic-assisted total hip arthroplasty (THA) have recently been recommended as a viable treatment option for achieving accurate positioning of components. Yet, limited studies paid attention to the differences between the closed platform robotic system and the open platform robotic system. Hence, this study aimed to investigate clinical outcomes, radiographic outcomes, complication rates and learning curve of two systems. MATERIALS AND METHODS: We retrospectively included 62 patients (31 closed robotic system and 31 open robotic system) who underwent THA between February 2021 and January 2023. The demographics, operating time, cup positioning, complications and hip Harris score were evaluated. Learning curves of operation time was conducted using cumulative sum (CUSUM) analysis. RESULTS: There were no differences in surgical time (76.7 ± 12.1 min vs. 72.3 ± 14.8 min), estimated blood loss (223.2 ± 13.2 ml vs. 216.9 ± 17 ml) and Harris Hip score (HHS) between closed platform robotic system and the open platform robotic system. The closed robotic system and the open robotic system were associated with a learning curve of 9 cases and 7 cases for surgical time respectively, based on the satisfying rate of Lewinnek's safe zone outliers (1/31, 96.8%) and no occurrence of complication. Both robotic systems had significant reduction in overall surgical time, the duration of acetabulum registration, and estimated blood loss between learning phase and proficiency phase. CONCLUSION: The authors suggest that the surgical outcomes and safe zone outlier rate of the open robotic-assisted THA were similar to those of the closed robotic-assisted THA. These two robotic-assisted are associated with comparable learning curves and both have the precise positioning of acetabular component. From learning phase to proficiency phase, the rate of positions within the safe zone differed only marginally (88.9-100% vs. 85.7-100%) based on a rather low number of patients. This is not a statistically significant difference. Therefore, we suggest that THA undergoing with the robotic-assisted system is the relatively useful way to achieve planned acetabular cup position so far.

A novel machine learning-based programmed cell death-related clinical diagnostic and prognostic model associated with immune infiltration in endometrial cancer.

Background: To explore the underlying mechanism of programmed cell death (PCD)-related genes in patients with endometrial cancer (EC) and establish a prognostic model. Methods: The RNA sequencing data (RNAseq), single nucleotide variation (SNV) data, and corresponding clinical data were downloaded from TCGA. The prognostic PCD-related genes were screened and subjected to consensus clustering analysis. The two clusters were compared by weighted correlation network analysis (WGCNA), immune infiltration analysis, and other analyses. The least absolute shrinkage and selection operator (LASSO) algorithm was used to construct the PCD-related prognostic model. The biological significance of the PCD-related gene signature was evaluated through various bioinformatics methods. Results: We identified 43 PCD-related genes that were significantly related to prognoses of EC patients, and classified them into two clusters via consistent clustering analysis. Patients in cluster B had higher tumor purity, higher T stage, and worse prognoses compared to those in cluster A. The latter generally showed higher immune infiltration. A prognostic model was constructed using 11 genes (GZMA, ASNS, GLS, PRKAA2, VLDLR, PRDX6, PSAT1, CDKN2A, SIRT3, TNFRSF1A, LRPPRC), and exhibited good diagnostic performance. Patients with high-risk scores were older, and had higher stage and grade tumors, along with worse prognoses. The frequency of mutations in PCD-related genes was correlated with the risk score. LRPPRC, an adverse prognostic gene in EC, was strongly correlated with proliferation-related genes and multiple PCD-related genes. LRPPRC expression was higher in patients with higher clinical staging and in the deceased patients. In addition, a positive correlation was observed between LRPPRC and infiltration of multiple immune cell types. Conclusion: We identified a PCD-related gene signature that can predict the prognosis of EC patients and offer potential targets for therapeutic interventions.

Genome-wide transcriptomics and microRNAomics analyses uncover multi-faceted mechanisms to cope with copper stress in ancient macrobenthos amphioxus.

The mechanisms underlying the toxicity of environmental stress are unclear for marine macrobenthos. Copper/Cu has posed the most serious threats to amphioxus, an ancient and model benthic cephalochordate. Herein, a dynamic change in the physiological parameters (GR, SOD, ATP, and MDA) was detected with ROS accumulation in Branchiostoma belcheri exposed to 0.3 mg·L-1 Cu. Transcriptomes and microRNAomes of B. belcheri were generated to investigate the molecular mechanisms by which this amphioxus copes with Cu exposure. Time-specific genes identified at different time points after exposure were involved in the stimulus and immune response, detoxification and ionic homeostasis, aging and the nervous system, sequentially, with prolongation of exposure time, forming a dynamic process of molecular response to Cu stress. In total, 57 differentially expressed miRNAs were identified under Cu stress. Transcriptomics-miRNAomics analyses indicate that these miRNAs targeted genes associated with many key biological processes such as xenobiotics degradation, oxidative stress, and energy metabolism. The constructed miRNA-mRNA-pathway network uncovered a broad post-transcriptional regulatory mechanism in B. belcheri to cope with Cu stress. Overall, this integrated analyses show that enhanced defense response, accelerated ROS elimination, and repressed ATP production constitute a comprehensive strategy to cope with Cu toxicity in the ancient macrobenthos.

Polyp-Canal Reconstruction Reveals Evolution Toward Complexity in Corals.

Modern scleractinian corals are classified into robust, complex, and basal clades through comparative molecular studies. However, only few morphological or biological criteria can systematically determine the evolutionary trajectories of these major scleractinian coral clades. Here, we obtained the structural information of 21 scleractinian coral species representing robust and complex clades: High-resolution micro-computed tomography was used to reconstruct the polyp-canal systems in their colonies and to visualize the dynamic polyp growth processes. We found that the emergence of mesh-like canals may distinguish representatives of complex and robust clades. The differences in polyp-canal connections suggest distinct evolutionary trajectories among coral species: The formation of the canal network promoted the development of more complex coral structures, and coral polyps within this network formed calices of very similar volume, following precise axial growth directions. The influence of individual polyps on the coral colony becomes less significant as coral structures become more complex, and coral species with more complicated polyp-canal systems occupied niches more efficiently. This work supplements current evolutionary studies on reef-building corals, providing insight for further studies on coral growth patterns.

Researching the application of virtual reality in medical education: one-year follow-up of a randomized trial.

BACKGROUND: Compared with traditional tendon repair teaching methods, using a virtual reality (VR) simulator to teach tendon suturing can significantly improve medical students' exercise time, operation flow and operation knowledge. At present, the purpose of this study is to explore the long-term influence of VR simulator teaching on the practice performance of medical students. METHOD: This is a one-year long-term follow-up study of a randomized controlled study. A total of 117 participants who completed the initial study were invited to participate in the follow-up study. Participants in the VR group and the control group were required to complete a questionnaire developed by the authors and the teachers in the teaching and research department and to provide their surgical internship scores and Objective Structure Clinical Examination(OSCE) graduation scores. RESULTS: Of the 117 invitees, 108 completed the follow-up. The answers to the questions about career choice and study habits were more positive in the VR group than in the control group (p < 0.05). The total score for clinical practice in the VR group was better than that in the control group, and the difference was statistically significant (p < 0.05). In the OSCE examination, the scores for physical examination, suturing and knotting and image reading were higher in the VR group than in the control group, and the difference was statistically significant (p < 0.05). CONCLUSION: The results of the one-year long-term follow-up indicated that compared with medical students experiencing the traditional teaching mode, those experiencing the VR teaching mode had more determined career pursuit and active willingness to learn, better evaluations from teachers in the process of surgical clinical practice, and better scores in physical examination, suturing and knotting and image reading in the OSCE examination. In the study of nonlinear dynamics to cultivate a good learning model for medical students, the VR teaching model is expected to become an effective and stable initial sensitive element. TRIAL REGISTRATION: Chinese Clinical Trial Registry(25/05/2021, ChiCTR2100046648); http://www.chictr.org.cn/hvshowproject.aspx?id=90180 .

Behind the Silence of the Professional Classroom in Universities: Formation of Cognition-Practice Separation among University Students-A Grounded Theory Study in China.

Classroom silence is a negative form of classroom performance that is particularly prominent in the Chinese learner population. Existing research has mainly explored the silence phenomenon among Chinese university students in two types of learning contexts: overseas university classrooms and foreign language classrooms at local universities, without focusing on the Chinese undergraduates' reticence in courses mediated by native language at domestic universities. However, the last type is the most common habitat for Chinese university students' learning in higher education. Therefore, a sample of Chinese undergraduates majoring in education (n = 394) was recruited to determine the mechanisms of silence formation in professional classrooms. This study was based on grounded theory and in-depth interviews, and the recorded material was processed using NVivo 12. After a series of steps including open coding, axial coding, selective coding, and theoretical saturation testing, the core feature of the phenomenon of silence in professional classrooms of Chinese university students majoring in education was found to be the separation of students' cognition and speaking practice. Then, a theoretical model of the formation and development of the phenomenon of classroom silence in professional classrooms of these undergraduates was constructed. The study showed that these university students had professional perceptions of classroom silence and displayed strong opposition to it, but they continued to maintain silent classroom behavior under the combined influence of individual characteristics, classroom experience, and learning adjustment. Following this, implications for existing research and suggestions for future practice are discussed.

Construction and validation of web-based nomograms for detecting and prognosticating in prostate adenocarcinoma with bone metastasis.

Bone metastasis (BM) is one of the most common sites of metastasis in prostate adenocarcinoma (PA). PA with BM can significantly diminish patients' quality of life and result in a poor prognosis. The objective of this study was to establish two web-based nomograms to estimate the risk and prognosis of BM in PA patients. From the Surveillance, Epidemiology, and End Results (SEER) database, data on 308,332 patients diagnosed with PA were retrieved retrospectively. Logistic and Cox regression, respectively, were used to determine independent risk and prognostic factors. Then, We constructed two web-based nomograms and the results were validated by receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA) , and the Kaplan-Meier analyses. The independent risk factors for BM in PA patients included race, PSA, ISUP, T stage, N stage, brain, liver, lung metastasis, surgery, radiation and chemotherapy. The independent prognostic predictors for overall survival (OS) were age, marital status, PSA, ISUP and liver metastasis. Both nomograms could effectively predict risk and prognosis of BM in PA patients according to the results of ROC curves, calibration, and DCA in the training and validation sets. And the Kaplan-Meier analysis illustrated that the prognostic nomogram could significantly distinguish the population with different survival risks. We successfully constructed the two web-based nomograms for predicting the incidence of BM and the prognosis of PA patients with BM, which may assist clinicians in optimizing the establishment of individualized treatment programs and enhancing patients' prognoses.

How to advance China's carbon emission peak?- A comparative analysis of energy transition in China and the USA.

This paper investigates carbon emission peak in China based on a comparative analysis of energy transition in China and the United States (US). The LMDI model is adopted to decompose carbon emissions into several driving factors in 2000-2018 for China and the US. Gray forecasting and NAR neural network are combined to predict peak time and identify optimal transition paths. The factor decomposition indicates that energy intensity is the main inhibitory factor for increased carbon emissions, while economic growth and population size are contributors for increased carbon emissions. There are significant differences in the impact of structure effect on carbon emissions in the two countries. The industry decomposition indicates that industry development is a critical inhibitor for increased carbon emissions after 2014 in China. The growth of transport and agriculture are basically contributing to increase carbon emissions in China and the US. The forecast results illustrate that China could complete carbon emission peak by 2030 under the baseline scenario, with a peak volume of 11354.72Mt CO2. Under the industrial structure adjustment scenario, the carbon peak year may be advanced to 2028. While adjusting industrial structure and energy consumption structure at the same time, China could achieve carbon emission peak at 9918.21Mt CO2 in 2025.

Molecular identification and lipid mobilization role of adipokinetic hormone receptor in Spodoptera litura (F.).

Energy homeostasis is essential for organisms to maintain fluctuation in energy accumulation, mobilization. Lipids as the main energy reserve in insects, their metabolism is under the control of many physiological program. This study aimed to determine whether the adipokinetic hormone receptor (AKHR) was involved in the lipid mobilization in the Spodoptera litura. A full-length cDNA encoding AKHR was isolated from S. litura. The SlAKHR protein has a conserved seven-transmembrane domain which is the character of a putative G protein receptor. Expression profile investigation revealed that SlAKHR mRNA was highly expressed in immatural stage and abundant in fat body in newly emerged female adults. Knockdown of SlAKHR expression was achieved through RNAi by injecting double-stranded RNA (dsRNA) into the 6th instar larvae. The content of triacylgycerol (TAG) in the fat body increased significantly after the SlAKHR gene was knockdown. And decrease of TAG releasing to hemolymph with increase of free fatty acid (FFA) in hemolymph were observed when the SlAKHR gene was knowned-down. In addition, lipid droplets increased in fat body was also found. These results suggested that SlAKHR is critical for insects to regulate lipids metabolism.

Curriculum Leadership of Rural Teachers: Status Quo, Influencing Factors and Improvement Mechanism-Based on a Large-Scale Survey of Rural Teachers in China.

Revealing the general status quo of teacher curriculum leadership has great theoretical, policy, and practical significance. However, large-scale empirical investigations in this area are rare, and there is even less attention to the current situation of rural teacher curriculum leadership. Based on the survey of 2,966 rural teachers in 20 provinces of China, this paper presented the status quo of rural teacher curriculum leadership and examined influencing factors through multiple linear regression analysis. It was found that curriculum leadership of rural teachers was at a low level with backward leadership views, lack of practical ability, and low sense of identity. Regression analysis demonstrated that individual field factors had a significant impact on teachers' curriculum leadership. Specifically, the higher the teachers' leadership willingness, trust in others, and self-efficacy, the higher the curriculum leadership. The school field was also an important influential aspect. In particular, the formation of a common vision and teacher community by the school and the appropriate empowerment of the principal had a significant positive impact on the curriculum leadership of rural teachers. Based on these key findings, several improvement suggestions are put forward at the end, which can be used as references for other countries to develop improvement plans on rural teacher curriculum leadership.

Diverse and complex developmental mechanisms of early Ediacaran embryo-like fossils from the Weng'an Biota, southwest China.

The origin and early evolution of animal development remain among the many deep, unresolved problems in evolutionary biology. As a compelling case for the existence of pre-Cambrian animals, the Ediacaran embryo-like fossils (EELFs) from the Weng'an Biota (approx. 609 Myr old, Doushantuo Formation, South China) have great potential to cast light on the origin and early evolution of animal development. However, their biological implications can be fully realized only when their phylogenetic positions are correctly established, and unfortunately, this is the key problem under debate. As a significant feature of developmental biology, the cell division pattern (CDP) characterized by the dynamic spatial arrangement of cells and associated developmental mechanisms is critical to reassess these hypotheses and evaluate the diversity of the EELFs; however, their phylogenetic implications have not been fully realized. Additionally, the scarcity of fossil specimens representing late developmental stages with cell differentiation accounts for much of this debate too. Here, we reconstructed a large number of EELFs using submicron resolution X-ray tomographic microscopy and focused on the CDPs and associated developmental mechanisms as well as features of cell differentiation. Four types of CDPs and specimens with cell differentiation were identified. Contrary to the prevailing view, our results together with recent studies suggest that the diversity and complexity of developmental mechanisms documented by the EELFs are much higher than is often claimed. The diverse CDPs and associated development features including palintomic cleavage, maternal nutrition, asymmetric cell divisions, symmetry breaking, establishment of polarity or axis, spatial cell migration and differentiation constrain some, if not all, EELFs as total-group metazoans. This article is part of the theme issue 'The impact of Chinese palaeontology on evolutionary research'.

Outcomes of dual mobility articulation total hip arthroplasty in ipsilateral residual poliomyelitis.

BACKGROUND: Patients with poliomyelitis underwent total hip arthroplasty (THA) are known to be at higher risk of dislocation on account of muscular atrophy. This study aimed to investigate clinical outcomes, radiographic outcomes, complication rates, and survivorship of dual mobility THA in displaced femoral neck fractures of elderly with poliomyelitis. MATERIALS AND METHODS: We retrospectively included 17 patients (17 hips) with residual poliomyelitis who underwent THA with dual mobility articulation. Clinical outcomes were assessed with the visual analog scale (VAS) pain score, Oxford hip score, and University of California Los Angeles activity (UCLA) score. Radiographic outcomes were examined by radiographs. Complications and re-operations following THA were recorded. RESULTS: The mean follow-up period was 77.05 months. The mean VAS, Oxford hip score, and UCLA score were improved significantly. In all but one patient, no complications were occurred. Re-operation was carried out in one patient due to posterior dislocation. The Kaplan-Meier survivorship with an end point of re-operation for any reason was 94.1%. CONCLUSIONS: THA with dual mobility system is proved to be effective in strengthening stability and reducing the risk of dislocation, which is suitable for patients with neuromuscular disease. Hence, in elderly with residual poliomyelitis, dual mobility THA is a valid choice as a treatment for displaced femoral neck fractures.

Construction and Validation of Two Novel Nomograms for Predicting the Overall Survival and Cancer-Specific Survival of NSCLC Patients with Bone Metastasis.

BACKGROUND: Bone metastasis (BM) is the most common site of metastasis in non-small cell lung carcinoma (NSCLC). We aimed to construct and validate 2 novel nomograms predicting the 3-, 6-, and 12-months overall survival (OS) and cancer-specific survival (CSS). METHODS: The clinical data of 7480 patients between 2010 and 2016 were enrolled from the Surveillance, Epidemiology, and End Results database (SEER). The patients were allocated randomly to training and validation cohorts in a 7:3 ratio. Cox proportional hazards regression models were used to identify prognostic risk factors and establish 2 nomograms. The prediction accuracy of nomograms was assessed by C-index, the area under the ROC curve (AUC), and calibration curves. RESULTS: A total of 244998 NSCLC patients were identified between 2010 and 2016, with 7480 found with BM, accounting for 3.1%. Overall, 7480 patients were enrolled in the OS nomogram construction and were randomized to the training set (n = 5236) and the validation set (n = 2244). Age, sex, race, marital status, histology, grade, primary site, T stage, N stage, liver metastasis, surgery, radiotherapy, and chemotherapy were found to correlate with OS. A total of 7422 samples were included in the CSS nomogram construction, randomly grouped into training set (n = 5195) and the validation set (n = 2227). Age, sex, race, histology, grade, primary site, T stage, N stage, brain metastasis, liver metastasis, surgery, radiotherapy, and chemotherapy were associated with CSS. Two nomograms were conducted to predict the 3-, 6-, and 12-months OS and CSS. The ROC curves and exhibited good performance for predicting OS and CSS. CONCLUSION: We established and validated 2 high-performance nomograms to assist clinical doctors in making personalized treatment decisions.

Micro-CT reconstruction reveals the colony pattern regulations of four dominant reef-building corals.

Colonies are the basic geometric building blocks of coral reefs. However, the forming regulations of both colonies and reefs are still not understood adequately. Therefore, in this study, we reconstructed 25 samples using high-resolution micro-computed tomography to investigate coral growth patterns and parameters. Our skeleton and canal reconstructions revealed the characteristics of different coral species, and we further visualized the growth axes and growth rings to understand the coral growth directions. We drew a skeleton grayscale map and calculated the coral skeleton void ratios to ascertain the skeletal diversity, devising a method to quantify coral growth. On the basis of the three-dimensional (3D) reconstructions and growth parameters, we investigated the growth strategies of different coral species. This research increases the breadth of knowledge on how reef-building corals grow their colonies, providing information on reef-forming regulations. The data in this paper contain a large amount of coral growth information, which can be used in further research on reef-forming patterns under different conditions. The method used in this study can also be applied to animals with porous skeletons.

The role of routine postoperative laboratory tests following hip hemiarthroplasty for an elderly femoral neck fracture.

BACKGROUND: Performing postoperative laboratory tests following joint arthroplasty is a regular practice. However, the role of routine postoperative laboratory tests in primary hip arthroplasty is currently in doubt. This study aimed to assess the role of routine postoperative laboratory tests for femoral neck fractures in elderly patients who underwent hip hemiarthroplasty and to evaluate the risk factors for postoperative laboratory testing abnormalities and related interventions. METHODS: This retrospective study reviewed 735 consecutive patients with femoral neck fractures (FNFs) who underwent hip hemiarthroplasty at a single tertiary academic organization. Patient characteristic features and laboratory testing values were recorded. Logistic regression models were calculated to identify risk factors. RESULTS: A total of 321 elderly patients (> 75 years of age) were ultimately enrolled for analysis. Abnormal postoperative laboratory tests were found in 265 patients (82.6%). Only a minority of the included patients (7.5%) needed medical intervention to treat postoperative laboratory testing abnormalities. Multivariate logistic regression analysis reported that a higher Charlson comorbidity index (CCI) (P = 0.03), abnormal preoperative haemoglobin level (P < 0.01), higher intraoperative blood loss (P < 0.01) and less frequent tranexamic acid use (P = 0.05) were risk factors for abnormal postoperative laboratory tests. Furthermore, a higher CCI has been identified as a risk factor for patients needing clinical interventions related to laboratory abnormalities. CONCLUSIONS: Because 92.5% of laboratory tests did not influence postoperative management, the authors suggest that routine laboratory tests after hip hemiarthroplasty for FNFs are less instructive for the majority of elderly patients. Nevertheless, for patients with identified risk factors, postoperative laboratory tests are still required to identify the abnormalities that need to be managed.

Genome-Wide Expression Difference of MicroRNAs in Basal Cell Carcinoma.

Distinct expression of the miRNAs has rarely been explored in basal cell carcinoma (BCC) of skin, and the regulatory role of miRNAs in BCC development remains quite opaque. Here, we collected control tissues from adjacent noncancerous skin (n = 15; control group) and tissues at tumor centers from patients with cheek BCC (n = 15; BCC group) using punch biopsies. After six small RNA sequencing- (sRNA-seq-) based miRNA expression profiles were generated for both BCC and controls, including three biological replicates, we conducted comparative analysis on the sRNA-seq dataset, discovering 181 differentially expressed miRNAs (DEMs) out of the 1,873 miRNAs in BCCs. In order to validate the sRNA-seq data, expression of 15 randomly selected DEMs was measured using the TaqMan probe-based quantitative real-time PCR. Functional analysis of predicted target genes of DEMs in BCCs shows that these miRNAs are primarily involved in various types of cancers, immune response, epithelial growth, and morphogenesis, as well as energy production and metabolism, indicating that BCC development is caused, at least in part, by changes in miRNA regulation for biological and disease processes. In particular, the "basal cell carcinoma pathways" were found to be enriched by predicted DEM targets, and regulatory relationships between DEMs and their targeted genes in this pathway were further uncovered. These results revealed the association between BCCs and abundant miRNA molecules that regulate target genes, functional modules, and signaling pathways in carcinogenesis.

Diabetes mellitus accelerates the progression of osteoarthritis in streptozotocin-induced diabetic mice by deteriorating bone microarchitecture, bone mineral composition, and bone strength of subchondral bone.

BACKGROUND: The purpose of this study was to develop an optimal diabetes-osteoarthritis (DM-OA) mouse model to validate that diabetes aggravates osteoarthritis (OA) and to evaluate the microarchitecture, chemical composition, and biomechanical properties of subchondral bone (SB) as a consequence of the DM-OA-induced damage induced. METHODS: Mice were randomly divided into three groups: DM-OA group, OA group, and sham group. Blood glucose levels, body weight, and food intake of all animals were recorded. Serum calcium (Ca) and osteocalcin (OCN) levels were compared in the three groups. The messenger ribonucleic acid (mRNA) and protein expression of key regulators for bone metabolism were detected. A semi-quantitative grading system [Osteoarthritis Research Society International (OARSI)] was used to evaluate cartilage and SB degeneration. Microspectroscopy, microindentations, micro-computed tomography (CT) imaging, and fracture load of compression testing were also used to evaluate trabecular SB properties. RESULTS: Glycemic monitoring and pancreas pathological results indicated stable high blood glucose and massive destruction of pancreas and islet cells in the DM-OA group. Serum levels of bone specific alkaline phosphatase (ALP-B) and tartrate-resistant acid phosphatase 5b (TRACP-5b) in the DM-group were higher than those of the other two groups while levels of serum Ca and OCN were lower. Meanwhile, the protein and mRNA expression of osteoblast-specific biomarkers [osteoprotegerin/receptor activator of nuclear factor kappa-B ligand (OPG/RANKL) ratio, collagen type I (COL-I), Runt-related transcription factor 2 (RUNX-2), OCN] were suppressed, and osteoclast-specific biomarkers [sclerostin (SOST)] was elevated in the DM-OA group. The mineral-to-collagen ratio, microindentation elastic modulus, hardness, micro-architectural parameters, bone mineral density, and fracture load of SB trabecular bone of the DM-OA group joint were lower than those of the other two groups. On the other hand, The OARSI score, trabecular spacing, and structural model index of the DM-OA group joint were higher than those of the other two groups. CONCLUSIONS: The glycemic and pancreatic pathological results indicated that the DM-OA model was a simple and reliable model induced by streptozotocin (STZ) and surgery. The results revealed the mechanisms through which diabetes accelerates OA; that is, by damaging and deteriorating the functions of SB, including its microarchitecture, chemical composition, and biomechanical properties.

Use of a Virtual Reality Simulator for Tendon Repair Training: Randomized Controlled Trial.

BACKGROUND: Virtual reality (VR) simulators have become widespread tools for training medical students and residents in medical schools. Students using VR simulators are provided with a 3D human model to observe the details by using multiple senses and they can participate in an environment that is similar to reality. OBJECTIVE: The aim of this study was to promote a new approach consisting of a shared and independent study platform for medical orthopedic students, to compare traditional tendon repair training with VR simulation of tendon repair, and to evaluate future applications of VR simulation in the academic medical field. METHODS: In this study, 121 participants were randomly allocated to VR or control groups. The participants in the VR group studied the tendon repair technique via the VR simulator, while the control group followed traditional tendon repair teaching methods. The final assessment for the medical students involved performing tendon repair with the "Kessler tendon repair with 2 interrupted tendon repair knots" (KS) method and the "Bunnell tendon repair with figure 8 tendon repair" (BS) method on a synthetic model. The operative performance was evaluated using the global rating scale. RESULTS: Of the 121 participants, 117 participants finished the assessment and 4 participants were lost to follow-up. The overall performance (a total score of 35) of the VR group using the KS method and the BS method was significantly higher (P<.001) than that of the control group. Thus, participants who received VR simulator training had a significantly higher score on the global rating scale than those who received traditional tendon repair training (P<.001). CONCLUSIONS: Our study shows that compared with the traditional tendon repair method, the VR simulator for learning tendon suturing resulted in a significant improvement of the medical students in the time in motion, flow of operation, and knowledge of the procedure. Therefore, VR simulator development in the future would most likely be beneficial for medical education and clinical practice. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100046648; http://www.chictr.org.cn/hvshowproject.aspx?id=90180.

Whole-genome resequencing reveals the pleistocene temporal dynamics of Branchiostoma belcheri and Branchiostoma floridae populations.

Global climatic fluctuations governed the ancestral demographic histories of species and contributed to place the current population status into a more extensive ecological and evolutionary context. Genetic variations will leave unambiguous signatures in the patterns of intraspecific genetic variation in extant species since the genome of each individual is an imperfect mosaic of the ancestral genomes. Here, we report the genome sequences of 20 Branchiostoma individuals by whole-genome resequencing strategy. We detected over 140 million genomic variations for each Branchiostoma individual. In particular, we applied the pairwise sequentially Markovian coalescent (PSMC) method to estimate the trajectories of changes in the effective population size (N e) of Branchiostoma population during the Pleistocene. We evaluated the threshold of sequencing depth for proper inference of demographic histories using PSMC was ≥25×. The PSMC results highlight the role of historical global climatic fluctuations in the long-term population dynamics of Branchiostoma. The inferred ancestral N e of the Branchiostoma belcheri populations from Zhanjiang and Xiamen (China) seawaters was different in amplitude before the first (mutation rate = 3 × 10-9) or third glaciation (mutation rate = 9 × 10-9) of the Pleistocene, indicating that the two populations most probably started to evolve in isolation in their respective seas after the first or third glaciation of the Pleistocene. A pronounced population bottleneck coinciding with the last glacial maximum was observed in all Branchiostoma individuals, followed by a population expansion occurred during the late Pleistocene. Species that have experienced long-term declines may be especially vulnerable to recent anthropogenic activities. Recently, the industrial pollution and the exploitation of sea sand have destroyed the harmonious living environment of amphioxus species. In the future, we need to protect the habitat of Branchiostoma and make full use of these detected genetic variations to facilitate the functional study of Branchiostoma for adaptation to local environments.