KinomeMETA: meta-learning enhanced kinome-wide polypharmacology profiling.

Kinase inhibitors are crucial in cancer treatment, but drug resistance and side effects hinder the development of effective drugs. To address these challenges, it is essential to analyze the polypharmacology of kinase inhibitor and identify compound with high selectivity profile. This study presents KinomeMETA, a framework for profiling the activity of small molecule kinase inhibitors across a panel of 661 kinases. By training a meta-learner based on a graph neural network and fine-tuning it to create kinase-specific learners, KinomeMETA outperforms benchmark multi-task models and other kinase profiling models. It provides higher accuracy for understudied kinases with limited known data and broader coverage of kinase types, including important mutant kinases. Case studies on the discovery of new scaffold inhibitors for membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase and selective inhibitors for fibroblast growth factor receptors demonstrate the role of KinomeMETA in virtual screening and kinome-wide activity profiling. Overall, KinomeMETA has the potential to accelerate kinase drug discovery by more effectively exploring the kinase polypharmacology landscape.

Is 3D-printed self-stabilizing endoprosthesis reconstruction without supplemental fixation following total sacrectomy a viable approach for sacral tumours?

PURPOSE: The spinopelvic reconstruction poses significant challenges following total sacrectomy in patients with malignant or aggressive benign bone tumours encompassing the entire sacrum. In this study, we aim to assess the functional outcomes and complications of an integrated 3D-printed sacral endoprostheses featuring a self-stabilizing design, eliminating the requirement for supplemental fixation. METHODS: We retrospectively analyzed patients with sacral tumours who underwent total sacrectomy followed by reconstruction with 3D-printed self-stabilizing endoprosthesis. Clinically, we evaluated functional outcomes using the 1993 version of the musculoskeletal tumour society (MSTS-93) score. Perioperative and postoperative complications were also documented. RESULTS: 10 patients met final inclusion criteria. The median age was 49 years (range, 31-64 years). The median follow-up time was 26.5 months (range, 15-47 months). Median postoperative functional MSTS-93 was 22.5 (range, 13-25). The median operation time was 399.5 min (305-576 min), and the median intraoperative blood loss was and 3200 ml (2400-7800 ml). Complications include wound dehiscence in one patient, bowel, bladder, and sexual dysfunction in four patients, cerebrospinal fluid leak in one patient, and tumour recurrence in one patient. There were no mechanical complications related to the endoprosthesis at the last follow-up. CONCLUSION: The utilization of 3D-printed self-stabilizing endoprosthesis proved to be a viable approach, yielding satisfactory short-term outcomes in patients undergoing total sacral reconstruction without supplemental fixation.

3D-Printed custom-made hemipelvic endoprosthetic reconstruction following periacetabular tumor resection: utilizing a novel classification system.

BACKGROUND: Customized 3D-printed pelvic implants with a porous structure have revolutionized periacetabular pelvic defect reconstruction after tumor resection, offering improved osteointegration, long-term stability, and anatomical fit. However, the lack of an established classification system hampers implementation and progress. METHODS: We formulated a novel classification system based on pelvic defect morphology and 3D-printed hemipelvis endoprostheses. It integrates surgical approach, osteotomy guide plate and prosthesis design, postoperative rehabilitation plans, and perioperative processes. RESULTS: Retrospectively analyzing 60 patients (31 males, 29 females), we classified them into Type A (15 patients: Aa = 6, Ab = 9), Type B (27 patients: Ba = 15, Bb = 12), Type C (17 patients). All underwent customized osteotomy guide plate-assisted tumor resection and 3D-printed hemipelvic endoprosthesis reconstruction. Follow-up duration was median 36.5 ± 15.0 months (range, 6 to 74 months). The mean operating time was 430.0 ± 106.7 min, intraoperative blood loss 2018.3 ± 1305.6 ml, transfusion volume 2510.0 ± 1778.1 ml. Complications occurred in 13 patients (21.7%), including poor wound healing (10.0%), deep prosthesis infection (6.7%), hip dislocation (3.3%), screw fracture (1.7%), and interface loosening (1.7%). VAS score improved from 5.5 ± 1.4 to 1.7 ± 1.3, MSTS-93 score from 14.8 ± 2.5 to 23.0 ± 5.6. Implant osseointegration success rate was 98.5% (128/130), with one Type Ba patient experiencing distal prosthesis loosening. CONCLUSION: The West China classification may supplement the Enneking and Dunham classification, enhancing interdisciplinary communication and surgical outcomes. However, further validation and wider adoption are required to confirm clinical effectiveness.

Hierarchically Porous Few-Layer Carbon Nitride and Its High H+ Selectivity for Efficient Photocatalytic Seawater Splitting.

Photocatalysts for seawater splitting are severely restricted because of the presence of multiple types of ions in seawater that cause corrosion and deactivation. As a result, new materials that promote adsorption of H+ and hinder competing adsorption of metal cations should enhance utilization of photogenerated electrons on the catalyst surface for efficient H2 production. One strategy to design advanced photocatalysts involves introduction of hierarchical porous structures that enable fast mass transfer and creation of defect sites that promote selective hydrogen ion adsorption. Herein, we used a facile calcination method to fabricate the macro-mesoporous C3N4 derivative, VN-HCN, that contains multiple nitrogen vacancies. We demonstrated that VN-HCN has enhanced corrosion resistance and elevated photocatalytic H2 production performance in seawater. Experimental results and theoretical calculations reveal that enhanced mass and carrier transfer and selective adsorption of hydrogen ions are key features of VN-HCN that lead to its high seawater splitting activity.

Advanced Pelvic Girdle Reconstruction with three dimensional-printed Custom Hemipelvic Endoprostheses following Pelvic Tumour Resection.

PURPOSE: Resection of pelvic bone tumours and subsequent pelvic girdle reconstruction pose formidable challenges due to the intricate anatomy, weight-bearing demands, and significant defects. 3D-printed implants have improved pelvic girdle reconstruction by enabling precise resections with customized guides, offering tailored solutions for diverse bone defect morphology, and integrating porous surface structures to promote osseointegration. Our study aims to evaluate the long-term efficacy and feasibility of 3D-printed hemipelvic reconstruction following resection of malignant pelvic tumours. METHODS: A retrospective review was conducted on 96 patients with primary pelvic malignancies who underwent pelvic girdle reconstruction using 3D-printed custom hemipelvic endoprostheses between January 2017 and May 2022. Follow-up duration was median 48.1 ± 17.9 months (range, 6 to 76 months). Demographic data, imaging examinations, surgical outcomes, and oncological evaluations were extracted and analyzed. The primary endpoints included oncological outcomes and functional status assessed by the Musculoskeletal Tumor Society (MSTS-93) score. Secondary endpoints comprised surgical duration, intraoperative bleeding, pain control and complications. RESULTS: In 96 patients, 70 patients (72.9%) remained disease-free, 15 (15.6%) had local recurrence, and 11 (11.4%) succumbed to metastatic disease. Postoperatively, function improved with MSTS-93 score increasing from 12.2 ± 2.0 to 23.8 ± 3.8. The mean operating time was 275.1 ± 94.0 min, and the mean intraoperative blood loss was 1896.9 ± 801.1 ml. Pain was well-managed, resulting in substantial improvements in VAS score (5.3 ± 1.8 to 1.4 ± 1.1). Complications occurred in 13 patients (13.5%), including poor wound healing (6.3%), deep prosthesis infection (4.2%), hip dislocation (2.1%), screw fracture (1.0%), and interface loosening (1.0%). Additionally, all patients achieved precise implantation of customized prosthetics according to preoperative plans. T-SMART revealed excellent integration at the prosthesis-bone interface for all patients. CONCLUSION: The use of a 3D-printed custom hemipelvic endoprosthesis, characterized by anatomically designed contours and a porous biomimetic surface structure, offers a potential option for pelvic girdle reconstruction following internal hemipelvectomy in primary pelvic tumor treatment. Initial results demonstrate stable fixation and satisfactory mid-term functional and radiographic outcomes.

Advancements in Photothermal Therapy Using Near-Infrared Light for Bone Tumors.

Bone tumors, particularly osteosarcoma, are prevalent among children and adolescents. This ailment has emerged as the second most frequent cause of cancer-related mortality in adolescents. Conventional treatment methods comprise extensive surgical resection, radiotherapy, and chemotherapy. Consequently, the management of bone tumors and bone regeneration poses significant clinical challenges. Photothermal tumor therapy has attracted considerable attention owing to its minimal invasiveness and high selectivity. However, key challenges have limited its widespread clinical use. Enhancing the tumor specificity of photosensitizers through targeting or localized activation holds potential for better outcomes with fewer adverse effects. Combinations with chemotherapies or immunotherapies also present avenues for improvement. In this review, we provide an overview of the most recent strategies aimed at overcoming the limitations of photothermal therapy (PTT), along with current research directions in the context of bone tumors, including (1) target strategies, (2) photothermal therapy combined with multiple therapies (immunotherapies, chemotherapies, and chemodynamic therapies, magnetic, and photodynamic therapies), and (3) bifunctional scaffolds for photothermal therapy and bone regeneration. We delve into the pros and cons of these combination methods and explore current research focal points. Lastly, we address the challenges and prospects of photothermal combination therapy.

BDNF is a prognostic biomarker involved in immune infiltration of lung adenocarcinoma and is associated with brain metastasis.

Non-small cell lung cancer (NSCLC) is one of the leading causes of death worldwide. Brain metastases are a common complication of a wide range of human malignancies, particularly lung adenocarcinoma (LUAD). Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has been linked to several human malignancies and has been shown to promote LUAD tumorigenesis. However, its function in the tumour immune microenvironment (TIME) remains largely unexplored, especially in complex brain tissue environments. In this study, BDNF was found to be particularly increased in patients with advanced tumour stage, lymphatic metastasis, and distant metastasis, indicating a correlation with LUAD progression. We characterized the prognostic value of BDNF and defined BDNF as an unfavourable prognostic indicator through a common driver gene-independent mechanism in LUAD. Furthermore, patients with increased BDNF levels in primary LUAD might have a higher risk of developing brain metastasis (BM), and central nervous system (CNS) metastasis showed an elevated expression of BDNF compared to their matched primary lesions. Additionally, we investigated the interaction between BDNF and infiltrating immune cells in both primary lesions and paired BM using multiplex immunostaining. The results showed that BDNF might drive an immunosuppressive tumour microenvironment (TME) by re-education of tumour-associated macrophages (TAMs) toward a pro-tumorigenic M2 phenotype, particularly in BM. Our findings demonstrate that BDNF serves as an independent potential prognostic marker and correlates with BM in LUAD. As it is closely related to TAM polarization, BDNF may be a promising immune-related biomarker and molecular target in patients with LUAD.

Pelvic-girdle reconstruction with three-dimensional-printed endoprostheses after limb-salvage surgery for pelvic sarcomas: current landscape.

Resection of pelvic bone tumors and the subsequent reconstruction of the pelvic girdle pose challenges due to complex anatomy, load-bearing demands, and significant defects. 3D-printed implants have revolutionized pelvic girdle reconstruction by offering customized solutions, porous surface structures for precise resection with custom guides, and improved integration. Many tertiary medical centers have adopted 3Dprinted hemipelvic endoprostheses, leading to enhanced outcomes. However, most studies are limited to single centers, with a small number of cases and short follow-up periods. Additionally, the design of these implants often relies heavily on individual experience, resulting in a lack of uniformity and significant variation. To provide a comprehensive assessment of this technology, we conducted an analysis of existing literature, encompassing tumor resection classification, various types of prosthesis design, reconstruction concepts, and post-reconstruction functional outcomes.

The optimal strategy for 3D-printed uncemented endoprosthesis for the bone defect reconstruction of the distal radius, based on biomechanical analysis and retrospective cohort study.

INTRODUCTION: Prosthetic reconstruction after resecting giant cell tumor of bone (GCTB) of the distal radius has been proposed. However, this is generally associated with various complications. To improve the functional outcomes, we designed a three-dimensional (3D)-printed uncemented endoprosthesis. Meanwhile, using finite-element analysis and clinical observation, an optimization strategy was explored. MATERIALS AND METHODS: We retrospectively analyzed patients with Campanacci III or recurrent GCTB of the distal radius who underwent 3D-printed uncemented endoprosthesis reconstruction. Clinically, according to the different palmar tilts of the endoprosthesis, patients were divided into the biological angle (BA) group and the zero-degree (ZD) group. We recorded and evaluated the differences in functional outcomes and complications between the two groups. Biomechanically, four 3D finite-element models (normal and customized endoprostheses with three different implemented palmar tilts) were developed. RESULTS: We analyzed 22 patients (12 males and 10 females). The median follow-up period was 60 (range, 19-82) months. Of the 22 patients, 11 patients were included in the BA group and the remaining 11 patients were in the ZD group. Both groups showed no significant differences in the range of motion, Mayo score, and disabilities of the arm, shoulder, and hand scores postoperatively. The subluxation rate was significantly lower in the ZD group than in the BA group. The biomechanical results showed similar stress and displacement distribution patterns in the normal and prosthetic reconstruction models. Additionally, the endoprosthesis with 0° palmar tilt showed better biomechanical performance. CONCLUSION: 3D-printed uncemented endoprosthesis provides acceptable midterm outcomes in patients undergoing distal radius reconstruction. Optimizing the design by decreasing the palmar tilt may be beneficial for decreasing the risk of wrist joint subluxation.

Three-Dimensional Multimodality Image Reconstruction as Teaching Tool for Case-based learning among medical postgraduates: a focus on primary pelvic bone Tumour Education.

BACKGROUND: Postgraduate medical education in oncology orthopedics confronts obstacles when instructing on pelvic tumors, primarily due to their intricate anatomy and the limitations of conventional teaching techniques. The employment of Three-dimensional multimodality imaging (3DMMI) can be considered a valuable teaching tool, as it gracefully elucidates the intricacies of pelvic anatomical structures and the interactions between tumors and surrounding tissues through three-dimensional imaging, thereby providing a comprehensive and nuanced perspective. This study aimed to assess the feasibility and effectiveness of incorporating 3DMMI in combination with a Case-Based Learning (CBL) approach for postgraduate education. METHODS: The study encompassed a 10-week course involving 90 surgical postgraduates, focusing on common pelvic tumor diseases. Students were assigned representative clinical cases, and each group created a PowerPoint presentation based on these cases. The core educational content included fundamental knowledge of pelvic anatomy, as well as clinical presentations, radiological features, and treatment principles of common pelvic tumor diseases. The research compared two groups: a traditional CBL group (n = 45) and a 3DMMI-CBL group (n = 45). The 3DMMI-CBL group had access to advanced imaging technology for better visualization. Various evaluations, including image interpretation, theoretical knowledge, and questionnaires, were used to assess the learning outcomes. RESULTS: The 3DMMI-CBL group outperformed the CBL group not only in the imaging diagnosis of common pelvic diseases but also in their mastery of the related theoretical knowledge. Student questionnaires indicated higher scores for the 3DMMI-CBL group in basic pelvic anatomy knowledge (8.08 vs. 6.62, p < 0.01), image interpretation (8.15 vs. 6.69, p < 0.01), learning efficiency (8.07 vs. 7.00, p < 0.01), clinical reasoning (7.57 vs. 6.77, p < 0.01), and learning interest (8.46 vs. 7.00, p < 0.01). Teacher questionnaires revealed that 3DMMI technology enhanced teachers' clinical knowledge, facilitated instruction, and increased overall satisfaction and interest in teaching. CONCLUSION: Our study introduced an enhancement to the conventional Case-Based Learning (CBL) model by incorporating 3DMMI technology for visualizing pelvic anatomy. In contrast to pure CBL, this adaptation improved teacher instruction, substantially heightened student engagement, ignited greater interest in learning, and boosted overall efficiency, ultimately leading to positive learning outcomes. Consequently, our study demonstrated the potential feasibility and acceptability of the 3DMMI-CBL teaching method for postgraduates in pelvic bone tumor education.

Is three-dimension-printed mesh scaffold an alternative to reconstruct cavity bone defects near joints?

PURPOSE: Reconstruction of cavity bone defects after curettage of benign bone tumours around the joint remains challenging. We designed a novel 3D-printed mesh scaffold as a substitute for bone cement, aiming to support the articular surface, protect the subchondral bone, and reduce complication rates. METHODS: We retrospectively analyzed seven patients who received curettage and reconstruction using a 3D-printed mesh scaffold between January 2020 and June 2021. Pain and function were evaluated using the 10-cm Visual Analogue Scale (VAS) score and the 1993 version of the Musculoskeletal Tumor Society (MSTS-93) score. Radiographs were used to evaluate articular surface supporting, subchondral bone protection, and complications. RESULTS: The median functional MSTS-93 and VAS scores were both improved after surgery, and the median 3D-printed mesh scaffold volume was smaller than the median defect volume. Articular surface supporting, subchondral bone preservation, and osteogenesis were observed post-operatively. No related complications were observed during the last follow-up. CONCLUSIONS: The 3D-printed mesh scaffold provided sufficient mechanical support for the articular surface and protected the subchondral bone. We recommended the 3D-printed mesh structure as an alternative to repair cavity bone defects around joints.

Preparation of a novel monoclonal antibody against active components of PHA-L from Phaseolus vulgaris and its functional characteristics.

BACKGROUND: Leukocyte phytohemagglutinin (PHA-L), derived from the L4 tetramer of PHA, has been frequently employed as a mitogen to induce T lymphocyte proliferation in vitro. The biological application of PHA-L in cancer diagnosis and treatment has gained traction in recent years. However, it has been noted that PHA-L obtained using traditional procedures has a massive amount of impurities or toxic components, which interfere with the activity of PHA-L. Preparation of a monoclonal antibody against active PHA-L is a significant tool for studying PHA-L's function and therapeutic potential. RESULTS: We successfully prepared monoclonal antibodies against the active components of PHA-L based on the whole PHA-L protein as an antigen, and found that monoclonal antibody 3C1C6G11 can be employed in western blot, immunofluorescence, and immunohistochemistry detection. Importantly, preliminary result shows that the mAb 3C1C6G11 may prevent PHA-L-induced cell aggregation and AICD (activation-induced cell death). CONCLUSIONS: The monoclonal antibody mAb 3C1C6G11 prepared in this study can be used as an effective tool for detecting PHA-L active components, investigating PHA-L's function and antineoplastic application.

Protective effect of ischaemic postconditioning combined with nicorandil on myocardial ischaemia‒reperfusion injury in diabetic rats.

BACKGROUND: The diabetic heart exhibits a high sensitivity to ischaemia/reperfusion (I/R) injury. Diabetes mellitus (DM) can affect the efficacy of cardioprotective interventions and reduce the therapeutic potential of existing treatment options. This study aimed to investigate the feasibility of shifting from monotherapy to combination therapy in diabetic myocardial I/R injury. METHODS: 6-8 week rats were randomized into 10 groups: sham, I/R, ischaemia postconditioning (I-Post), nicorandil (Nic), combination therapy (I-Post + Nic), DM sham, DM I/R, DM I-Post, DM Nic and DM I-Post + Nic. The extent of myocardial injury was clarified by measuring CK-MB and NO levels in plasma, ROS content in myocardial tissues, and TTC/Evans Blue staining to assess the area of myocardial infarction. Pathological staining of cardiac tissue sections were performed to clarify the structural changes in myocardial histopathology. Finally, Western blotting was performed to detect the phosphorylation levels of some key proteins in the PI3K/Akt signalling pathway in myocardial tissues. RESULTS: We confirms that myocardial injury in diabetic I/R rats remained at a high level after treatment with I-Post or nicorandil alone. I-Post combined with nicorandil showed better therapeutic effects in diabetic I/R rats, and the combined treatment further reduced the area of myocardial injury in diabetic I/R rats compared with I-Post or nicorandil treatment alone (P < 0.001), as well as the levels of the myocardial injury markers CK-MB and ROS (P < 0.001); it also significantly increased plasma NO levels. Pathological staining also showed that diabetic rats benefited significantly from the combination therapy. Further mechanistic studies confirmed this finding. The protein phosphorylation levels of PI3K/Akt signalling pathway in the heart tissue of diabetic I/R rats were significantly higher after the combination treatment than after one treatment alone (all P < 0.05). CONCLUSION: I-Post combined with nicorandil treatment maintains effective cardioprotection against diabetic myocardial I/R injury by activating the PI3K/Akt signalling pathway.

Design and simulation analysis of the AOTF full-Stokes imaging spectropolarimeter.

In order to effectively improve the contrast of target identification, an acousto-optic tunable filter (AOTF) full-Stokes imaging spectropolarimeter is proposed, which can measure synchronously polarization information with each spectral band in real time. The full-Stokes vectors are obtained by the division-of-aperture polarization imaging system. The spectral bands are selected by RF of the AOTF electrically. Based on this system, a polarization error model is established, and the influence of the key polarization element angle error is analyzed. The results show that the measurement error increases with the increase of the polarization degree. When P=1, the influence of the azimuth angle error is greater than the retardance error under the same angle error. The results are helpful to find the variation law of the polarization error and provide a theoretical reference for the design of new types of full-Stokes imaging spectropolarimeters.

Synchronous lung and multiple soft tissue metastases developed from osteosarcoma of tibia: a rare case report and genetic profile analysis.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor with a highly metastatic propensity in children and young adolescents. The majority of metastases develope in the lung, while metastases to the extrapulmonary locations have rarely been discussed, especially in skeletal muscle. CASE PRESENTATION: We reported a young patient with pathologically diagnosed osteosarcoma of the right tibia who was initially treated with standard chemotherapy and complete surgical resection. However, pulmonary metastases and multiple soft tissue masses in skeletal muscle developed four years after the index surgical resection. Subsequently, a targeted next-generation sequencing assay based on an 806 oncogenes and tumor suppressor genes panel was performed to analyze genetic alterations in this patient with rare metastatic pattern. The genetic analysis revealed canonical somatic mutations of RB1 and germline variants of ALK (c.862 T > C), BLM (c.1021C > T), PTCH1 (c.152_154del), MSH2 (c.14C > A), RAD51C (c.635G > A). Using silico prediction programs, the germline variants of the MSH2 and RAD51C were predicted as "Possibly Damaging" by Polymorphism Phenotyping v2 (PolyPhen-2) and "Tolerated" by Sorting Intolerant from Tolerant (SIFT); BLM was classified as "Tolerated", while the germline variant of ALK was predicted to be pathogenic by both PolyPhen-2 and SIFT. CONCLUSIONS: Osteosarcoma with extrapulmonary metastases is rare, especially located in the skeletal muscle, which predicts a worse clinical outcome compared with lung-only metastases. The several novel variants of ALK, BLM, PTCH1 in this patient might expand the mutational spectrums of the osteosarcoma. All the results may contribute to a better understanding of the clinical course and genetic characteristics of osteosarcoma patients with metastasis.

Cementless curved endoprosthesis stem for distal femoral reconstruction in a Chinese population: a combined anatomical & biomechanical study.

BACKGROUND: The endoprosthetic knee reconstruction using a current universal femoral stem might not be suitable for local population due to the anatomical difference between Chinese and Western populations. We measured the anatomical parameters of Chinese femurs as reference for stem design, and proposed a cementless, curved, short endoprosthesis stem for the reconstruction of distal femur. This study analyzed the biomechanical performance of the newly designed stem aimed at the identification of better operative strategy. METHODS: The CT-scanning data of femurs derived from 96 healthy Chinese volunteers were imported into the Mimics software, and a segmental measurement strategy was applied to evaluate the radius of curvature (ROC) of the femoral medullary cavity. Then, 4 kinds of endoprosthetic replacement models were created based on the measurement results. Model A: the distal tumor resected femora + straight stem A; Model B: the distal tumor resected femora + curved stem B; Model C: the distal tumor resected femora + curved stem C; Model D: the distal tumor resected femora + curved stem D. Finally, the mechanical difference among these models were compared by finite element analysis. RESULTS: The mean femoral ROC of Segment1, 2, 3, 4, 5 measured in the present study was 724.5 mm, 747.5 mm, 1016.5 mm, 1286.5 mm, and 1128 mm, respectively. Based on the femoral ROC of Segment2, the stem ROC of the curved stem B, C, and D was designed as 475 mm, 700 mm, and 1300 mm, respectively. Generally, all endoprosthetic replacement models showed a normal-like stress distribution on the femurs. However, compared to the straight stem, the biomimetic curved stem showed better biomechanical performance both in terms of reducing the extent of the stress shielding of the femur and in terms of minimizing the stress distribution of the implant. CONCLUSIONS: The uncemented, curved, short stem with suitable ROC can perfectly match the Chinese femoral canal morphology which has better mechanical properties than the conventional femoral stem. Thus, this newly designed femoral stem might be an optimized method for treatment of malignant femoral tumours in the Chinese populations in the case that the numerical results are supported by future experimental studies.

Three-dimensional printed customized uncemented unipolar prosthesis combined with ligament reconstruction for tumorous defect of the distal femur in children.

BACKGROUND: Hemiarthroplasty following tumor resection of the distal femur in children provides a chance to preserve the proximal tibial physis for limb elongation. Based on three-dimensional (3D) printing technology, the uncemented unipolar prosthesis with joint stability reinforced structures (JSRSs) was custom-designed for our cases. This study aimed to describe the design and assess the short-term outcomes of this refined prosthetic hemiarthroplasty. METHODS: Seven patients (four females and three males) received 3D-printed customized uncemented unipolar prosthesis for hemiarthroplasty after removal of the distal femur, from September 2019 to October 2020 at our Orthopedics department. The limb function, growth of the preserved proximal tibial physis, joint stability, and limb length discrepancy (LLD) were assessed. Complications were recorded. RESULTS: Six patients survived with no evidence of metastasis or local recurrence at the last follow-up, and one patient died of lung metastasis at 19 months postoperatively. Follow-up ranged from 19 to 32 months, with an average of 26 months. Elongation of the tibia was observed in all cases. At the last follow-up, four patients exhibited equal growth length compared with the healthy contralateral tibia. LLD ranged from 0.8 to 1.6 cm with a mean of 1.3 cm. The average knee range of motion was 95.3° of flexion and 4.5° of extension. All patients achieved satisfactory postoperative limb function with a mean MSTS score of 25.8. The results of the drawer, Lachman, and pivot shift tests were negative in all patients. During follow-up, painless joint space narrowing was observed in two patients. The screw for ligament fixation loosened in one of the seven patients at 17 months postoperatively. No subluxation of the joint, angular deformity, or breakage of the implant was detected in the remaining patients. CONCLUSIONS: 3D-printed customized uncemented unipolar prosthesis with JSRS would be a good choice for reconstructing tumorous defect in the distal femur in children.

Effects of neoadjuvant chemotherapy combined with customized tumor-type total knee arthroplasty on immune function and limb function in the treatment of malignant bone tumors around the knee joint.

Objectives: To explore the effects of neoadjuvant chemotherapy combined with customized tumor-type total knee arthroplasty (TKA) on immune function and limb function in the treatment of malignant bone tumors around the knee joint. Methods: Sixty-one patients with malignant bone tumors around the knee joint treated in Sichuan Provincial Orthopedics Hospital from February 2018 to February 2020 were retrospectively enrolled and divided into two groups according to treatment methods. The differences in immune function indexes before and after treatment were compared between the two groups. And their postoperative complications were recorded. Results: Before treatment, no significant difference can be observed in the comparison, values between the two groups (P>0.05); After treatment, the levels in Group-A were higher than before treatment (P<0.05), but the levels were not different from those before treatment (P>0.05). In contrast, the levels in Group-B were higher than before treatment and higher than that in Group-A, while the level of CD8+ was lower than before treatment and lower than that in Group-A (P<0.05). At six months postoperatively, no significant difference was observed in the excellent and good rate of limb function between the two groups (P>0.05). There were no differences in the incidence of postoperative prosthesis complications and the incidence of adverse chemotherapy reactions between the two groups (P>0.05). Conclusion: Neoadjuvant chemotherapy combined with customized tumor-type TKA for knee malignant bone tumors is an excellent safety treatment for malignant bone tumors around the knee joint, boasting a variety of benefits, such as significantly ameliorating the immune function of patients and promoting the recovery of limb function, which is worthy of clinical application.

Wnt7b-induced Sox11 functions enhance self-renewal and osteogenic commitment of bone marrow mesenchymal stem cells.

As a profoundly anabolic regulator of bone, Wnt7b is well acknowledged to enhance osteoblast activities. Here, we report that bone marrow mesenchymal stem cells (BMSCs) are another important population responding to Wnt7b. In this study, we systematically investigated the in vivo role of Wnt7b in BMSCs using transgenic mice, high-throughput RNA-seq, immunohistochemistry, RT-qPCR, and in situ hybridization. These methods led us to uncover that Sox11 is induced via Wnt7b in BMSCs. Colony formation assay, flow cytometry, EdU incorporation labeling, RT-qPCR, and Western blot were conducted to detect the self-renewal capacity of BMSCs. Alkaline phosphatase staining, alizarin red staining, and ex vivo BMSCs transplantation were utilized to detect the osteogenic ability of BMSCs. ChIP-qPCR, shRNAs, and immunofluorescence staining were utilized to investigate the underlying mechanisms. Consequently, bone-derived Wnt7b was found to decrease in osteoporosis and elevate in bone fracture healing. During bone fracture healing, Wnt7b was particularly expressed in the mesenchymal cells residing within healing frontiers. RNA-seq data of Wnt7b-overexpressed bones uncovered the significant upregulation of Sox11. Histological results further unveiled that Sox11 is specifically increased in BMSCs. Wnt7b-induced Sox11 was demonstrated to reinforce both self-renewal and osteogenic differentiation of BMSCs. Mechanistically, Wnt7b activates the Ca2+ -dependent Nfatc1 signaling to directly induce Sox11 transcription, which in turn activates the transcriptions of both proliferation-related transcription factors (Ccnb1 and Sox2) and osteogenesis-related factors (Runx2, Sp7) in BMSCs. It is intriguing that this Wnt7b-Sox11 signaling in BMSCs is ß-Catenin-independent. Overall, this study provides brand new insights of Wnt7b in bone formation, namely, Wnt7b can enhance both self-renewal and osteogenic differentiation of BMSCs via inducing Sox11. These findings present a new crosstalk between Wnt and Sox signaling in BMSCs.

Three-dimensional-printed customized prosthesis for pubic defect: clinical outcomes in 5 cases at a mean follow-up of 24 months.

BACKGROUND: Pubic defects resulting from type III hemipelvectomy are commonly not reconstructed due to the need to preserve the weight-bearing axis. However, the opening of the anterior pelvic ring will inevitably lead to increased pelvic instability. To improve long-term pelvic stability, three-dimensional (3D)-printed customized prostheses were designed to reconstruct pubic defects. This study presents and evaluates the short-term clinical outcomes and complications from the use of this construct. METHODS: Five patients who underwent type III hemipelvectomy and 3D-printed customized prosthesis reconstruction at our institution between 2017 and 2019 were retrospectively analysed. Operation time and blood loss during the operation were recorded. Local and functional recovery was assessed. Prosthetic position and osseointegration were evaluated. Oncology results and complications were recorded. RESULTS: The prostheses consisted of three with stems and two without. The mean follow-up time was 23.6 months. At the last follow-up, all five patients were alive with no evidence of disease. No deep infections or local recurrence had occurred. The mean blood loss and mean intraoperative time were 1680 ml and 294 min, respectively. The mean functional MSTS score at the final follow-up was 29.8. Fretting wear around the prosthetic stem was found in 3 patients, while bone wear on the normal-side pubis was found in 2 patients. Osseointegration was observed in all patients. CONCLUSIONS: 3D-printed customized prostheses for reconstructing pubic bone defects after type III hemipelvectomy showed acceptable early outcomes. The good outcomes were inseparable from the precision prosthesis design, strict surgical procedures, and sensible postoperative management.