Does a Video-Based and 3D Animation Hybrid Learning System Improve Teaching Outcomes in Orthopedic Surgery? A Randomized Controlled Trial.

OBJECTIVE: This study aims to evaluate the instructional efficacy of a 3D Surgical Training System (3DSTS), which combines real surgical footage with high-definition 3D animations, against conventional surgical videos and textbooks in the context of orthopedic proximal humerus fracture surgeries. DESIGN: Before the experiment, 89 participants completed a pre-educational knowledge assessment. They were then randomized into 3 groups: the 3DSTS group (n = 30), the surgical video (SV) group (n = 29), and the textbook group (n = 30). After their respective teaching courses, all participants took a posteducational assessment and completed a perceived cognitive load test. The 3DSTS group also filled out a satisfaction survey. Once all assessments were finished, the SV and textbook groups were introduced to the 3DSTS course and subsequently completed a satisfaction survey. All statistical analyses were executed using IBM SPSS version 24 (IBM Corp., Armonk, NY). For data fitting normal distribution, we employed one-way analysis of variance (one-way ANOVA) and Tukey HSD tests, whereas, for non-normally distributed data, we used Kruskal-Wallis H tests and Dunn's tests. The significance level for all tests was set at p < 0.05. SETTING: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, P. R. China. PARTICIPANTS: About 89 doctors who undergoing standardized residents training. RESULT: The initial assessment scores among the three groups were comparable, showing no significant statistical difference. Post-education revealed a marked difference in the scores, with the 3DSTS group outperforming both the SV and textbook groups. Specifically, the 3DSTS group exhibited statistically greater improvement in areas such as procedural steps, and specialized surgical techniques compared to the SV and textbook groups. During the 3DSTS teaching process, participants reported the least perceived cognitive load and expressed strong satisfaction, highlighting that the instructional materials are well-prepared, and considering this teaching method superior and more innovative than previous courses they had encountered. CONCLUSION: The 3D Surgical Training System, integrating real videos with 3D animations, significantly enhances orthopedic surgery education over conventional methods, providing improved comprehension, lower cognitive load, and standardized learning outcomes. Its efficacy and high participant satisfaction underscore its potential for broader adoption in surgical disciplines. This study is registered with ClinicalTrials. gov ID: ChiCTR2300074730.

New augmented reality remote for virtual guidance and education of fracture surgery: a retrospective, non-inferiority, multicenter cohort study.

BACKGROUND: The demand for telesurgery is rapidly increasing. Augmented reality (AR) remote surgery is a promising alternative, fulfilling a worldwide need in fracture surgery. However, previous AR endoscopic and Google Glass remotes remain unsuitable for fracture surgery, and the application of remote fracture surgery has not been reported. We aimed to evaluated the safety and clinical effectiveness of a new AR remote in fracture surgery. MATERIALS AND METHODS: This retrospective non-inferiority cohort study was conducted at three centres. Between January 1, 2018, and March 31, 2022, 800 patients who underwent fracture surgery were eligible for participation. The study enrolled 551 patients with fractures (132 patellae, 128 elbows, 126 tibial plateaus, and 165 ankles) divided into an AR group (specialists used AR to remotely guide junior doctors to perform surgeries) and a traditional non-remote group (specialists performed the surgery themselves). RESULTS: Among 364 patients (182 per group) matched by propensity score, seven (3.8%) in the AR group and four (3%) in the non-remote group developed complications. The 0.005 risk difference (95% confidence interval: -0.033 to 0.044) was below the pre-defined non-inferiority margin of a 10% absolute increase. A similar distribution in the individual components of all complications was found between the groups. Hierarchical analysis following propensity score matching revealed no statistical difference between the two groups regarding functional results at 1-year follow-up, operative time, amount of bleeding, number of fluoroscopies, and injury surgery interval. A Likert scale questionnaire showed positive results (median scores: 4-5) for safety, efficiency, and education. CONCLUSION: This study is the first to report that AR remote surgery can be as safe and effective as that performed by a specialist in person for fracture surgery, even without the physical presence of a specialist, and is associated with improving the skills and increasing the confidence of junior surgeons. This technique is promising for remote fracture surgery and other open surgeries, offering a new strategy to address inadequate medical care in remote areas.

Isolation, identification, and induced differentiation of satellite cells from skeletal muscle of adult tree shrews.

A method for the in vitro isolation, purification, identification, and induced differentiation of satellite cells from adult tree shrew skeletal muscle was established. The mixed enzyme digestion method and differential adhesion method were used to obtain skeletal muscle satellite cells, which were identified and induced to differentiate to verify their pluripotency. The use of a mixture of collagenase II, hyaluronidase IV, and DNase I is an efficient method for isolating adult tree shrew skeletal muscle satellite cells. The P3 generation of cells had good morphology, rapid proliferation, high viability, and an "S"-shaped growth curve. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence staining indicated that marker genes or proteins were expressed in skeletal muscle satellite cells. After myogenic differentiation was induced, multiple-nucleated myotubes were observed, and the MyHC protein was expressed. The expression of myogenic marker genes changed with the differentiation process. After the induction of adipogenic differentiation, orange-red lipid droplets were observed, and the expression of adipogenic marker genes increased gradually with the differentiation process. In summary, satellite cells from adult tree shrew skeletal muscle were successfully isolated using a mixed enzyme digestion method, and their potential for differentiation into myogenic and adipogenic cells was confirmed, laying a foundation for further in vitro study of tree shrew muscle damage.

Synthesis and biological evaluation of capsaicin analogues as antioxidant and neuroprotective agents.

Capsaicin and its analogues 3a-3q were designed and synthesized as potential new antioxidant and neuroprotective agents. Many analogues exhibited good antioxidant effects, and some showed more potent free radical scavenging activities than the positive drug quercetin (IC50 = 8.70 ± 1.75 µM for DPPH assay and 13.85 ± 2.87 µM for ABTS assay, respectively). The phenolic hydroxyl of capsaicin analogues was critical in determining antioxidant activity. Among these compounds, 3k displayed the most potent antioxidant activity. Cell vitality tests revealed that the representative compound 3k was good at protecting cells from H2O2-induced oxidative damage at low concentrations (cell viability increased to 90.0 ± 5.5% at 10 µM). In addition, the study demonstrated that 3k could reduce intracellular ROS accumulation and increase GSH levels to prevent H2O2-induced oxidative stress in SY5Y cells. In the mitochondrial membrane potential assay, 3k significantly increased the MMP level of SY5Y cells treated with H2O2 and played an anti-neuronal cell death role. These results provide a promising strategy to develop novel capsaicin analogues as potential antioxidant and neuroprotective agents.

Deep learning assisted diagnosis system: improving the diagnostic accuracy of distal radius fractures.

Objectives: To explore an intelligent detection technology based on deep learning algorithms to assist the clinical diagnosis of distal radius fractures (DRFs), and further compare it with human performance to verify the feasibility of this method. Methods: A total of 3,240 patients (fracture: n = 1,620, normal: n = 1,620) were included in this study, with a total of 3,276 wrist joint anteroposterior (AP) X-ray films (1,639 fractured, 1,637 normal) and 3,260 wrist joint lateral X-ray films (1,623 fractured, 1,637 normal). We divided the patients into training set, validation set and test set in a ratio of 7:1.5:1.5. The deep learning models were developed using the data from the training and validation sets, and then their effectiveness were evaluated using the data from the test set. Evaluate the diagnostic performance of deep learning models using receiver operating characteristic (ROC) curves and area under the curve (AUC), accuracy, sensitivity, and specificity, and compare them with medical professionals. Results: The deep learning ensemble model had excellent accuracy (97.03%), sensitivity (95.70%), and specificity (98.37%) in detecting DRFs. Among them, the accuracy of the AP view was 97.75%, the sensitivity 97.13%, and the specificity 98.37%; the accuracy of the lateral view was 96.32%, the sensitivity 94.26%, and the specificity 98.37%. When the wrist joint is counted, the accuracy was 97.55%, the sensitivity 98.36%, and the specificity 96.73%. In terms of these variables, the performance of the ensemble model is superior to that of both the orthopedic attending physician group and the radiology attending physician group. Conclusion: This deep learning ensemble model has excellent performance in detecting DRFs on plain X-ray films. Using this artificial intelligence model as a second expert to assist clinical diagnosis is expected to improve the accuracy of diagnosing DRFs and enhance clinical work efficiency.

Deep learning system assisted detection and localization of lumbar spondylolisthesis.

Objective: Explore a new deep learning (DL) object detection algorithm for clinical auxiliary diagnosis of lumbar spondylolisthesis and compare it with doctors' evaluation to verify the effectiveness and feasibility of the DL algorithm in the diagnosis of lumbar spondylolisthesis. Methods: Lumbar lateral radiographs of 1,596 patients with lumbar spondylolisthesis from three medical institutions were collected, and senior orthopedic surgeons and radiologists jointly diagnosed and marked them to establish a database. These radiographs were randomly divided into a training set (n = 1,117), a validation set (n = 240), and a test set (n = 239) in a ratio of 0.7 : 0.15: 0.15. We trained two DL models for automatic detection of spondylolisthesis and evaluated their diagnostic performance by PR curves, areas under the curve, precision, recall, F1-score. Then we chose the model with better performance and compared its results with professionals' evaluation. Results: A total of 1,780 annotations were marked for training (1,242), validation (263), and test (275). The Faster Region-based Convolutional Neural Network (R-CNN) showed better precision (0.935), recall (0.935), and F1-score (0.935) in the detection of spondylolisthesis, which outperformed the doctor group with precision (0.927), recall (0.892), f1-score (0.910). In addition, with the assistance of the DL model, the precision of the doctor group increased by 4.8%, the recall by 8.2%, the F1-score by 6.4%, and the average diagnosis time per plain X-ray was shortened by 7.139 s. Conclusion: The DL detection algorithm is an effective method for clinical diagnosis of lumbar spondylolisthesis. It can be used as an assistant expert to improve the accuracy of lumbar spondylolisthesis diagnosis and reduce the clinical workloads.

Traumatic brain injury stimulates sympathetic tone-mediated bone marrow myelopoiesis to favor fracture healing.

Traumatic brain injury (TBI) accelerates fracture healing, but the underlying mechanism remains largely unknown. Accumulating evidence indicates that the central nervous system (CNS) plays a pivotal role in regulating immune system and skeletal homeostasis. However, the impact of CNS injury on hematopoiesis commitment was overlooked. Here, we found that the dramatically elevated sympathetic tone accompanied with TBI-accelerated fracture healing; chemical sympathectomy blocks TBI-induced fracture healing. TBI-induced hypersensitivity of adrenergic signaling promotes the proliferation of bone marrow hematopoietic stem cells (HSCs) and swiftly skews HSCs toward anti-inflammation myeloid cells within 14 days, which favor fracture healing. Knockout of ß3- or ß2-adrenergic receptor (AR) eliminate TBI-mediated anti-inflammation macrophage expansion and TBI-accelerated fracture healing. RNA sequencing of bone marrow cells revealed that Adrb2 and Adrb3 maintain proliferation and commitment of immune cells. Importantly, flow cytometry confirmed that deletion of ß2-AR inhibits M2 polarization of macrophages at 7th day and 14th day; and TBI-induced HSCs proliferation was impaired in ß3-AR knockout mice. Moreover, ß3- and ß2-AR agonists synergistically promote infiltration of M2 macrophages in callus and accelerate bone healing process. Thus, we conclude that TBI accelerates bone formation during early stage of fracture healing process by shaping the anti-inflammation environment in the bone marrow. These results implicate that the adrenergic signals could serve as potential targets for fracture management.

The regulation of expression and splicing of transcription factors are related to the muscle damage caused by radiation in tree shrews.

Radiotherapy-induced muscle injury (RIMI) is a major complication of radiotherapy for nasopharyngeal carcinoma. Transcription factor (TF) expression and alternative splicing are crucial events in transcriptional and posttranscriptional regulation, respectively, and are known to be involved in key signaling pathways contributing to a variety of human disorders, including radiation injury. To investigate the TFs and alternative splicing events involved in RIMI, we constructed a tree shrew model as described previously in which the RIMI group received 20 Gy of irradiation on the tensor veli palatini (TVP) muscles. The irradiated muscles were evaluated by RNA sequencing (RNA-seq) 6 months later, and the results compared with those for normal TVP muscles. The alt5p and alt3p events were the two main types of differentially regulated alternative splicing events (RASEs) identified via the Splice sites Usage Variation Analysis (SUVA) software, and these RASEs were highly conserved in RIMI. According to functional enrichment analysis, the differentially RASEs were primarily enriched in pathways related to transcriptional regulation. Furthermore, we identified 16 alternative splicing TFs (ASTFs) in ASTF-differentially expressed gene (DEG) networks based on co-expression analysis, and the regulatory networks were chiefly enriched in pathways linked to cell proliferation and differentiation. This study revealed that RASEs and ASTF-DEG networks may both play important regulatory roles in gene expression network alteration in RIMI. Future studies on the targeting mechanisms and early interventions directed at RASEs and ASTF-DEG networks may aid in the treatment of RIMI.

Biomechanical comparison of intramedullary nail and plate osteosynthesis for extra-articular proximal tibial fractures with segmental bone defect.

Purpose: Proximal tibial fractures are common, but the current available internal fixation strategies remain debatable, especially for comminuted fractures. This study aimed to compare the biomechanical stability of three internal fixation strategies for extra-articular comminuted proximal tibial fractures. Methods: A total of 90 synthetic tibiae models of simulated proximal tibial fractures with segmental bone defects were randomly divided into three groups: Single lateral plating (LP), double plating (DP) and intramedullary nailing (IN). Based on the different number of fixed screws, the above three groups were further divided into nine subgroups and subjected to axial compression, cyclic loading and static torsional testing. Results: The subgroup of intramedullary nailing with five proximal interlocking screws showed the highest axial stiffness of 384.36 ± 35.00 N/mm. The LP group obtained the lowest axial stiffness performance with a value of 96.59 ± 16.14 N/mm. As expected, the DP group offered significantly greater biomechanical stability than the LP group, with mean static axial stiffness and mean torque increasing by approximately 200% and 50%, respectively. According to static torsional experiments, the maximum torque of the DP subgroup was 3,308.32 ± 286.21 N mm, which outperformed all other groups in terms of torsional characteristics. Conclusion: Utilizing more than four distal screws did not provide improved biomechanical stability in the LP or DP groups, while a substantial increase in the biomechanical stability of DP was obtained when an additional medial plate was used. For the intramedullary nailing group, increasing the number of proximal interlocking screws could significantly improve biomechanical stability, and the intramedullary nailing with three proximal interlocking screws had similar static and cyclic stiffness as the DP group. The intramedullary nailing with five proximal screws had better axial stability, whereas DP had better torsional stability.

Laminin α1 as a target for the treatment of epidural fibrosis by regulating fibrotic mechanisms.

Excessive proliferation and migration of fibroblasts in the lumbar laminectomy area can lead to epidural fibrosis, eventually resulting in failed back surgery syndrome. It has been reported that laminin α1, a significant biofunctional glycoprotein in the extracellular matrix, is involved in several fibrosis­related diseases, such as pulmonary, liver and keloid fibrosis. However, the underlying mechanism of laminin α1 in epidural fibrosis remains unknown. The present study aimed to explore the effect and mechanism of laminin α1 in fibroblast proliferation, apoptosis and migration, and epidural fibrosis. Following the establishment of a laminectomy model, hematoxylin and eosin, Masson's trichrome and immunohistochemical staining were performed to determine the degree of epidural fibrosis, the number of fibroblasts, collagen content and the epidural expression levels of laminin α1, respectively. Furthermore, a stable small interfering RNA system was used to knock down the expression of laminin α1 in fibroblasts. The transfection efficiency was confirmed by reverse transcription­quantitative PCR and immunofluorescence staining. Western blot analysis, scratch wound assay, EdU incorporation assay, flow cytometric analysis and Cell Counting Kit 8 assay were performed to assess the proliferation, apoptosis, migration and viability of fibroblasts, as well as the expression levels of the AKT/mechanistic target of rapamycin (mTOR) signaling­related proteins. In vivo experiments revealed that laminin α1 was positively and time­dependently associated with epidural fibrosis. In addition, laminin α1 knockdown attenuated cell proliferation, viability and migration, and promoted apoptosis. Furthermore, the results revealed that the activation of the AKT/mTOR signaling pathway was involved in the aforementioned processes. Overall, the current study illustrated the positive association between laminin α1 and epidural fibrosis, and also verified the effect of laminin α1 on fibroblast proliferation, apoptosis and migration. Furthermore, the results suggested that the AKT/mTOR signaling pathway may serve a significant role in regulating the behavior of laminin α1­induced fibroblasts.

Artificial intelligence to detect the femoral intertrochanteric fracture: The arrival of the intelligent-medicine era.

Objective: To explore a new artificial intelligence (AI)-aided method to assist the clinical diagnosis of femoral intertrochanteric fracture (FIF), and further compare the performance with human level to confirm the effect and feasibility of the AI algorithm. Methods: 700 X-rays of FIF were collected and labeled by two senior orthopedic physicians to set up the database, 643 for the training database and 57 for the test database. A Faster-RCNN algorithm was applied to be trained and detect the FIF on X-rays. The performance of the AI algorithm such as accuracy, sensitivity, miss diagnosis rate, specificity, misdiagnosis rate, and time consumption was calculated and compared with that of orthopedic attending physicians. Results: Compared with orthopedic attending physicians, the Faster-RCNN algorithm performed better in accuracy (0.88 vs. 0.84 ± 0.04), specificity (0.87 vs. 0.71 ± 0.08), misdiagnosis rate (0.13 vs. 0.29 ± 0.08), and time consumption (5 min vs. 18.20 ± 1.92 min). As for the sensitivity and missed diagnosis rate, there was no statistical difference between the AI and orthopedic attending physicians (0.89 vs. 0.87 ± 0.03 and 0.11 vs. 0.13 ± 0.03). Conclusion: The AI diagnostic algorithm is an available and effective method for the clinical diagnosis of FIF. It could serve as a satisfying clinical assistant for orthopedic physicians.

An Investigation of the Mechanisms of Radiation-Induced Muscle Injury in a Tree Shrew (Tupaia belangeri) Model.

Background: Animal models suitable for investigating mechanisms behind radiation-induced muscle injury are lacking. We developed a tree shrew model of such injury and investigated pathological changes and mechanisms. Methods: Animals were divided into control (n = 5), radiation-induced acute injury (n = 5), and radiation-induced chronic injury (n = 5) groups. Tensor veli palatini (TVP) muscles of acute injury and chronic injury groups were dissected under a microscope at 1 and 24 weeks after radiation therapy, respectively. TVP muscles were stained with HE and Masson to visualize pathological changes. ELISA was performed to measure oxidative injury. RT-qPCR and immunohistochemical staining was performed to measure expression levels of miR-206 and histone deacetylase 4 (HDAC4). Results: Compared to the control group, acute injury group showed a significant decrease in miR-206 expression (.061 ± .38, P < .05) and a significant increase in HDAC4 expression (37.05 ± 20.68, P < .05). Chronic injury group showed a significant decrease in miR-206 expression (.23 ± .19, P < .05) and a significant increase in HDAC4 expression (9.66 ± 6.12, P < .05). Discussion: A tree shrew model of radiation-induced muscle injury was established by exposing TVP muscle region to radiation of 20-Gy. Experimental results indicated that injury caused by radiation persisted despite gradual healing of the TVP muscle and miR-206 regulatory pathway plays a key role in regulating radiation-induced muscle injury.

Applications of Mixed Reality Technology in Orthopedics Surgery: A Pilot Study.

Objective: The aim of this study is to explore the potential of mixed reality (MR) technology in the visualization of orthopedic surgery. Methods: The visualization system with MR technology is widely used in orthopedic surgery. The system is composed of a 3D imaging workstation, a cloud platform, and an MR space station. An intelligent segmentation algorithm is adopted on the 3D imaging workstation to create a 3D anatomical model with zooming and rotation effects. This model is then exploited for efficient 3D reconstruction of data for computerized tomography (CT) and magnetic resonance imaging (MRI). Additionally, the model can be uploaded to the cloud platform for physical parameter tuning, model positioning, rendering and high-dimensional display. Using Microsoft's HoloLens glasses in combination with the MR system, we project and view 3D holograms in real time under different clinical scenarios. After each procedure, nine surgeons completed a Likert-scale questionnaire on communication and understanding, spatial awareness and effectiveness of MR technology use. In addition to that, the National Aeronautics and Space Administration Task Load Index (NASA-TLX) is also used to evaluate the workload of MR hologram support. Results: 1) MR holograms can clearly show the 3D structures of bone fractures, which improves the understanding of different fracture types and the design of treatment plans; 2) Holograms with three-dimensional lifelike dynamic features provide an intuitive communication tool among doctors and also between doctors and patients; 3) During surgeries, a full lesion hologram can be obtained and blended in real time with a patient's virtual 3D digital model in order to give surgeons superior visual guidance through novel high-dimensional "perspectives" of the surgical area; 4) Hologram-based magnetic navigation improves the accuracy and safety of the screw placement in orthopaedics surgeries; 5) The combination of mixed reality cloud platform and telemedicine system based on 5G provides a new technology platform for telesurgery collaboration. Results of qualitative study encourage the usage of MR technology for orthopaedics surgery. Analysis of the Likert-scale questionnaire shows that MR adds significant value to understanding and communication, spatial awareness, learning and effectiveness. Based on the NASA TLX-scale questionnaire results, mixed reality scored significantly lower under the "mental," "temporal," "performance," and "frustration" categories compared to usual 2D. Conclusion: The integration of MR technology in orthopaedic surgery reduces the dependence on surgeons' experience and provides personalized 3D visualization models for accurate diagnosis and treatment of orthopaedic abnormalities. This integration is clearly one of the prominent future development directions in medical surgery.

Identification and functional characterization of potential oncofetal targets in human hepatocellular carcinoma.

Here, we present a detailed protocol for the identification of potential oncofetal targets for hepatocellular carcinoma (HCC) patients through a hepatocyte differentiation model and a sorafenib refractory cell-line-derived xenograft model. We describe the procedures of tumor sphere formation, organoid generation, and subcutaneous tumor formation for functional studies. We then detail the procedures of immunohistochemistry and immunofluorescence for examination of changes in lineage-specific markers. Finally, we describe the development of antibody-based therapeutics targeting tumor lineage plasticity in HCC. For complete details on the use and execution of this protocol, please refer to Kong et al. (2021).1.

Clinical effects of the combination of Traditional Chinese and Western Medicines on coronavirus disease 2019: a systematic review and Meta-analysi.

OBJECTIVE: To explore the clinical efficacy of the combination of Traditional Chinese and Western Medicines for the treatment of coronavirus disease 2019 (COVID-19). METHODS: Studies were identified in six popular medical databases. RESULTS: Thirteen studies were included. The results showed that combined treatment with Traditional Chinese and Western Medicines can reduce the probability of progression from mild to severe disease [RR = 0.34, 95% confidence interval (CI) (0.18, 0.65)] (P = 0.001) and improve the clinical cure rate [RR = 0.17, 95% CI (0.05, 0.28)] (P = 0.004). The use of an integrated treatment strategy shortened the time to the remission of fever [WMD = －1.27, 95% CI (－1.67, －0.92)](P < 0.001) and improved the incidences of the disappearance of fever and fatigue [RR = 1.25, 95% CI (1.06, 1.47) (P = 0.007); RR = 1.49, 95% CI (1.13, 1.97) (P = 0.004)]. CONCLUSION: A combined treatment strategy is effective for COVID-19.

Mixed reality assists the fight against COVID-19.

Coronavirus disease 2019 (COVID-19) made a huge effect globally. With the assistance of mixed reality (MR) technology, complicated clinical works became easier to carry out and the condition had been greatly improved with high-tech advantages such as improved convenience, better understanding and communication, higher security, and medical resource saving. This study aimed to introduce one kind of MR application in the fight against COVID-19 and anticipate more feasible smart healthcare applications to enhance our strength for the final victory.

A 3D Hologram With Mixed Reality Techniques to Improve Understanding of Pulmonary Lesions Caused by COVID-19: Randomized Controlled Trial.

BACKGROUND: The COVID-19 outbreak has now become a pandemic and has had a serious adverse impact on global public health. The effect of COVID-19 on the lungs can be determined through 2D computed tomography (CT) imaging, which requires a high level of spatial imagination on the part of the medical provider. OBJECTIVE: The purpose of this study is to determine whether viewing a 3D hologram with mixed reality techniques can improve medical professionals' understanding of the pulmonary lesions caused by COVID-19. METHODS: The study involved 60 participants, including 20 radiologists, 20 surgeons, and 20 medical students. Each of the three groups was randomly divided into two groups, either the 2D CT group (n=30; mean age 29 years [range 19-38 years]; males=20) or the 3D holographic group (n=30; mean age 30 years [range 20=38 years]; males=20). The two groups completed the same task, which involved identifying lung lesions caused by COVID-19 for 6 cases using a 2D CT or 3D hologram. Finally, an independent radiology professor rated the participants' performance (out of 100). All participants in two groups completed a Likert scale questionnaire regarding the educational utility and efficiency of 3D holograms. The National Aeronautics and Space Administration Task Load Index (NASA-TLX) was completed by all participants. RESULTS: The mean task score of the 3D hologram group (mean 91.98, SD 2.45) was significantly higher than that of the 2D CT group (mean 74.09, SD 7.59; P<.001). With the help of 3D holograms, surgeons and medical students achieved the same score as radiologists and made obvious progress in identifying pulmonary lesions caused by COVID-19. The Likert scale questionnaire results showed that the 3D hologram group had superior results compared to the 2D CT group (teaching: 2D CT group median 2, IQR 1-2 versus 3D group median 5, IQR 5-5; P<.001; understanding and communicating: 2D CT group median 1, IQR 1-1 versus 3D group median 5, IQR 5-5; P<.001; increasing interest: 2D CT group median 2, IQR 2-2 versus 3D group median 5, IQR 5-5; P<.001; lowering the learning curve: 2D CT group median 2, IQR 1-2 versus 3D group median 4, IQR 4-5; P<.001; spatial awareness: 2D CT group median 2, IQR 1-2 versus 3D group median 5, IQR 5-5; P<.001; learning: 2D CT group median 3, IQR 2-3 versus 3D group median 5, IQR 5-5; P<.001). The 3D group scored significantly lower than the 2D CT group for the "mental," "temporal," "performance," and "frustration" subscales on the NASA-TLX. CONCLUSIONS: A 3D hologram with mixed reality techniques can be used to help medical professionals, especially medical students and newly hired doctors, better identify pulmonary lesions caused by COVID-19. It can be used in medical education to improve spatial awareness, increase interest, improve understandability, and lower the learning curve. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100045845; http://www.chictr.org.cn/showprojen.aspx?proj=125761.

A de novo mutation of the SOX10 gene associated with inner ear malformation in a Guangxi family with Waardenburg syndrome type II.

OBJECTIVE: Waardenburg syndrome type 2 (WS2) is a rare neural-crest disorder, characterized by heterochromic irides or blue eyes and sensorineural hearing loss. The aim of this study was to analyze the clinical features and investigate the genetic cause of WS2 in a small family from Guangxi Zhuang Autonomous region. METHODS: Whole-exome sequencing and mutational analysis were used to identify disease-causing genes in this family. RESULTS: A de novo missense mutation, C.355C > T (p. Arg119Cys), in exon 2 of SOX10 was related to inner ear malformation in the proband and identified by whole exon sequencing, but this mutation was absent in normal controls and any public databases. According to nucleic acid sequence and protein bioinformatic analysis, this mutation is considered the cause of WS2 without neurologic involvement in the proband. CONCLUSIONS: Our findings provide an accurate genetic diagnosis, counseling, and rehabilitation for family members and may contribute to further genotype-phenotype correlation studies of the SOX10 gene.

Targeting tumor lineage plasticity in hepatocellular carcinoma using an anti-CLDN6 antibody-drug conjugate.

Tumor lineage plasticity is emerging as a critical mechanism of therapeutic resistance and tumor relapse. Highly plastic tumor cells can undergo phenotypic switching to a drug-tolerant state to avoid drug toxicity. Here, we investigate the transmembrane tight junction protein Claudin6 (CLDN6) as a therapeutic target related to lineage plasticity for hepatocellular carcinoma (HCC). CLDN6 was highly expressed in embryonic stem cells but markedly decreased in normal tissues. Reactivation of CLDN6 was frequently observed in HCC tumor tissues as well as in premalignant lesions. Functional assays indicated that CLDN6 is not only a tumor-associated antigen but also conferred strong oncogenic effects in HCC. Overexpression of CLDN6 induced phenotypic shift of HCC cells from hepatic lineage to biliary lineage, which was more refractory to sorafenib treatment. The enhanced tumor lineage plasticity and cellular identity change were potentially induced by the CLDN6/TJP2 (tight junction protein 2)/YAP1 (Yes-associated protein 1) interacting axis and further activation of the Hippo signaling pathway. A de novo anti-CLDN6 monoclonal antibody conjugated with cytotoxic agent (Mertansine) DM1 (CLDN6-DM1) was developed. Preclinical data on both HCC cell lines and primary tumors showed the potent antitumor efficiency of CLDN6-DM1 as a single agent or in combination with sorafenib in HCC treatment.