Objective:We designed and applied a novel, bionic megaprosthesis for distal femur, which substituted the hinged articulation with an artificial ligament and a constrained tibial insert in order to maintain articular stability and reduce stress and the risks of wearing, loosening and breakage.Methods:We reviewed the cases of distal femoral osteosarcoma in children population who were initially treated in our center during 2019. Twelve cases of bionic distal femoral prosthesis (bionic group) and 21 cases of fixed-hinge distal femoral prosthesis (control group) were included. In the bionic group, there were six female and six male with the mean age as 8.8±2.6 y. One patient had pathological fracture. Staging according to Enneking system included 1 case of stage IIA, 10 cases of stage IIB and 1 case of stage III. In the control group, there were seven female and fourteen male with the mean age as 8.6±2.2 y. Pathological fracture was seen in three cases. Staging included 15 cases of stage IIB and 6 cases of stage III.We investigated the peri-operative safety, oncological outcome, complication profiles and post-operative functional status of the bionic prosthesis by comparing the baseline data, operative data, and oncological and prosthetic outcomes between the two groups.Results:The two groups were comparable in terms of baseline data including gender, age, height, weight and onset duration, and operative data including duration of operation (126.7±27.9 min vs 143.3±38.9 min, P=0.203), intra-operative hemorrhage (162.5±212.3 ml vs 247.6±175.6 ml, P=0.224) and duration of wound drainage (6.3±2.4 d vs 6.4±3.4 d, P=0.908). The mean follow-up duration of bionic group was 16.0±4.7 months, during which time three patients had systemic progression and one of them died of disease. Another patient had local recurrence and subluxation of the prosthesis that was treated by amputation. Subluxation might be related to the huge tumor mass and excessive resection of the quadriceps femoris. As for the control group, the mean follow-up duration was 12.7±4.5 months. Three patients had systemic progression and all patients were still alive by last follow-up. Local recurrence was seen in two patients and was treated by excision. No prosthetic complications were seen in the control group. The averaged range of motion (ROM) was greater in the bionic group than that in the control group (120.6°±13.6° vs 92.0°±7.7°, P<0.05), but the MSTS 93 scores were similar between groups (29.1±0.9 vs 29.5±0.6, P=0.337). Conclusion:Compared with the fixed-hinge distal femoral prosthesis, the bionic prosthesis had good peri-operative safety, did not increase the risks of prosthetic complications, and could achieve a better range of motion and a similar functional status based on the results of short-term follow-up.

Obiective:To investigate the design, the key points of surgery and the outcome of short-term follow-up of hemi-elbow-arthroplastic bionic total humeral prosthesis by using 3D-print.Methods:The clinical data of 8 patients with humerus malignant tumor who underwent total humerus resection and a 3D-printed auxiliary hemi-elbow-arthroplastic total humeral prosthesis replacement from March 2018 to March 2020 at Peking University People's Hospital were retrospectively analyzed. The operative data, oncological outcome, complication profiles of prosthesis and functional status of all 8 patients were also analyzed. There were 3 males and 5 females with a mean age of 5-37 years. Histological diagnosis included 5 cases of osteosarcoma, 2 cases of Ewing's sarcoma and 1 case of chondrosarcoma.Results:The time for production of the prosthesis was (9.8±2.7) d, the operation time was (209±23) min and intraoperative hemorrhage was (569±173) ml. All the prostheses were implanted successfully and no patients experienced intraoperative complications. While 2 patients had postoperative complications, 1 case of temporary palsy of radial nerve and 1 case of local recurrence. LARS artificial ligament or hernia patch was used to reconstruct joint capsule and tendon-ligament attached around the elbow and shoulder joint. The flexion and extension of the elbow was (118±15)° (100-140°) and (11±9)° (0-25°), and the abduction and anteflexion of the shoulder was (28±12)° (15-50°) and (26±9)° (15-40°), respectively. The postoperative Musculoskeletal Tumor Society (MSTS)-93 scale score was (24.1±1.5) scores. The median follow-up time was 17 months (12-32 months), 7 patients had disease-free survival and 1 patient survived with tumor.Conclusions:The novel 3D-printed total humeral prosthesis with hemi-elbow-arthroplasty has a good perioperative safety, which is effective in restoring the function of elbow joint, solving the problem of stress concentration of ulnar marrow lever of total elbow joint prosthesis and lowering long-term wear rate and loosening rate of prosthesis.

Objective:To evaluate the safety and short-term clinical postoperative functional outcomes of a novel 3D-printed porous prosthesis of the distal tibia for the bone defect after tumorectomy.Methods:From December 2017 to December 2019, a total of eight patients diagnosed with malignant bone tumor of the distal tibia were enrolled in this study. All cases received standard preoperative chemotherapy, after which osteosarcoma resection was performed and ankle arthrodesis was reconstructed using a 3D-printed prosthesis developed by our medical center. The contact surface between the distal part of the prosthesis and the talus is a 3D-printed porous surface, which is conducive to ankle fusion. The length of the prosthesis is adjusted by the conical mounting part of the modular prosthesis. The proximal part of the prosthesis can be fixed either biologically or with bone cement. At postoperative follow-up, the function of the fused ankle was assessed by radiographs and the monthly Musculoskeletal Tumor Society (MSTS) score.Results:Of the 8 patients, 5 were male and 3 were female, aged 8-29 years (mean 16.1±7.4 years), including 7 osteoblastic osteosarcomas and 1 telangiectatic osteosarcoma. Among the procedures, the mean length of osteotomy was 16 cm (11-20 cm). The method of fixation of the proximal part of the prosthesis included one case with 3D-printing of trabecular metal bone, one case with autogenous fibular graft, and six cases with bone cement. All patients were followed up for 7-39 months (mean 15.6±10.5 months). The distal prosthesis and talus were completely fused in all cases. The mean fusion duration was 4.3±0.7 months. The mean MSTS score was 84.2%±3.0% (mean 80%-90%). No tumor recurrence, wound complications, or prosthesis loosening were observed during the follow-up period.Conclusion:The novel 3D-printed distal tibial prosthesis is a safe and effective technique for reconstruction of a massive bone defect after tumorectomy of a malignant bone tumor, with high fusion rate, few complications, and satisfactory postoperative function.

Objective:To investigate the clinical efficacy of cement-in-cement (CiC) technique for endoprosthetic revision surgeries of noninfectious causes around the knee.Methods:All of 128 patients who had received cement-in-cement technique for endoprosthetic revision from February 2002 to August 2020 including 71 males and 57 females, whose mean age was 33.5±15.4 years (range, 8-77 years). 128 patients included 73 cases of osteosarcoma, 38 cases of giant cell tumors, 8 cases of undifferentiated sarcoma, 4 cases of chondrosarcoma, 2 cases of Ewing sarcoma, 2 cases of fibrosarcoma and 1 case of synovial sarcoma, with 105 cases in distal femur and 23 cases in proximal tibia. The failure mode classification included 64 cases of aseptic loosening, 47 cases of structure failure and 17 cases of tumor progression. 16 out of the 19 endoprosthese failure after the first cement-in-cement procedure received a second cement-in-cement procedure. The survival of revised prostheses, duration of the operation, the amount of blood loss, epidemiological data, complications and limb function were enrolled and statistical analyzed.Results:The mean follow-up from CiC revision was 127±33 months (range, 6-326 months). There were 25 (19.5%) complications for the first CiC procedure and 19 (14.8%) of the 25 complications lead to the protheses failure including 5 (3.9%) structure failure, 6 (4.7%) aseptic loosening, 2 (1.6%) tumor recurrence and 6 (4.7%) infection. The other 6 cases included 5 poor superficial wound healing and 1 patellar ligament rupture. All were recovered after debridement and tendon repair. The cumulative survival rates of first CiC procedure were 85.0%, 76.6% and 70.7% at 5, 10 and 15 years, respectively. Limb salvage rate was 97.7%. Sixteen of the 19 cases received a second CiC revision. The mean operative time (206±51 min vs. 258±41 min, t=3.18, P=0.399), blood loss (596±217.99 ml vs. 621±245.84 ml, t=0.30, P=0.926) and the median MSTS 93 score (26.38±2.47 vs. 25.06±2.11, t=1.61, P=0.376) of the first and second CiC procedure for the 16 cases were similar. Conclusion:CiC technique is a repeatable, conservative and viable option for endoprosthetic revision surgeries of noninfectious causes around the knee, with acceptable prosthetic survival rate, complication rate and limb function.

Objective:To investigate the outcome of surgical treatment of malignant tumor at the distal tibial after reconstruction with modular hinged ankle prosthesis.Methods:The data of 9 patients with malignant tumor at the distal tibia at Musculoskeletal Tumor Center of PKUPH from June 2020 to November 2021 were analyzed retrospectively. They were male patients with age of 17 (14, 24) years (range 11-56 years). There were five tumors at the left sides and four at the right sides. There were eight patients with osteosarcoma who received the neo-chemotherapy. Among eight osteosarcomas, one was Enneking IIA and seven Enneking IIB. Furthermore, there was only one patient with renal carcinama and with solitary metastatic lesion at the distal tibia. After the resection of tumor at the distal tibia, talus cartilage was removed and talus component was fixed by lag screws. The proper tibia component was used to restore the defect of tibia and the reduction of tibia and talus components were performed. The following clinical data were collected: baseline demographic features, surgical and follow-up data. The baseline demographic features included gender, age, side, lung or/and other metastasis at initial diagnosis, Enneking stage or systematic progression for renal carcinama, histological type. The surgical data included: surgery time, blood loss, length of bone involved by the tumor, prosthesis type. Monitoring data was also recorded: complications (ankle pain when loading, talar collapse, component loosing, infection and wound dehiscence), local recurrence, pulmonary and systematic metastasis, radiological image and the function at the last follow-up (MSTS and VAS evaluation).Results:Among these nine patients, the average blood loss was 245.6±103.9 ml (range 100-400 ml) and the mean surgery time was 178.9±56.9 mins (range 120-300 min). No patient was lost during the follow-up period and the average follow-up was 21.4±5.6 months (range 12.5-27.2 months). The excision length of tibia was 14 (11, 17) cm (range 11-28 cm). There were one case with 2# prosthetic base, three cases with 3# and five cases with 4#. Five had cement fixation of prosthetic stem and four had the pressing fixation. No pulmonary and other organ metastasis occurred among eight patients with osteosarcoma and one patient with distal tibia matastasis of renal carcinama. One patient with OShad the local recurrence and received the resection. One sustained the deep infection after four months and received the removal of prosthesis and spacer implant. At the final follow-up, except one with deep infection and receiving the removal of prosthesis and spacer implant, eight patients were assessed for the function. The average MSTS was 97.1%±3.3% (range 93%-100%). The VAS of all patients was 0. One patient with prosthesis removal had no functional evaluation. At the final follow-up, all patients walked without crutch. No breakage and loosening of prosthetic stem, talar collapse, prosthetic sinking and ankle pain occurred at the final follow-up.Conclusion:The early satisfactory outcome can be obtained for patients with segmental defect after resection of malignant tumor at the distal tibia, who received the newly designed modular hinged ankle prosthesis. Meanwhile, it's worth promoting in the reconstruction of large segmental defect at the distal tibia.

Objective:To investigate the genomic manifestation and pathogenesis of osteosarcoma with different relapse pattens, which were respectively initially presented with bone metastasis or pulmonary metastasis.Methods:From May 1, 2021 to October 1, 2021, 38 fresh tumor specimens and some paraffin-embedded specimens of high-grade osteosarcoma were collected in Peking University People's Hospital, including 29 males and 9 females, aged 19.6±2.2 years (range, 6-61 years). Among the 38 cases, 12 cases had initial bone metastasis (group A) and 26 cases had initial lung metastasis (group B), of which 15 cases (40%, 15/38) had paired specimens of primary and metastatic lesions. Based on Illumina NovaSeq 6000, we analyzed whole-exome sequencing (WES) as well as transcriptome for osteosarcoma with paired samples in different relapse patterns. During all their treatment courses, we also collected their paired samples to reveal these tumors' evolution. We sought to redefine disease subclassifications for osteosarcoma based on genetic alterations and correlate these genetic profiles with clinical treatment courses to elucidate potential evolving cladograms.Results:We found that osteosarcoma in group A mainly carried single-nucleotide variations (83%, 10/12), displaying higher tumor mutation burden [4.9 (2.8, 12.0) & 2.4 (1.4, 4.5), P=0.010] and neoantigen load [743.0 (316.5, 1,034.5) & 128.5 (49.0, 200.5), P=0.003], while those in group B mainly exhibit structural variants (58%, 15/26). The mutation spectrum showed that there was a significant difference in age-related gene imprinting 1 between the bone metastasis group and the lung metastasis group ( P=0.005). Samples were randomly selected from group A (3 patients) to investigate immunologic landscape by multiplex immunohistochemistry, from which we noticed tertiary lymphatic structure from one patient from group A. High conservation of reported genetic sequencing over time was found in their evolving cladograms. Conclusion:Osteosarcoma with mainly single-nucleotide variations other than structural variants might exhibit biological behavior predisposing toward bone metastases with older in age as well as better immunogenicity in tumor microenvironment.

Formins are widely distributed in eukaryotes such as fungi, plants and animals. They play crucial roles in regulating the polymerization of actin, coordinating the synergistic interactions between actin and microtubules, and determining cell growth and morphology. Unlike formins from fungi and animals, plant formins have been evolved into two plant-specific types. Generally, type Ⅱ formins are believed to regulate the polarized growth of cells, and type Ⅰ formins may regulate the cell expansion and division processes. Recent studies on the function of plant formins suggest it is inappropriate to classify the function of formins purely based on their structures. This review summarizes the domain organization of formins and their corresponding functions, as well as the underpinning mechanisms. Furthermore, the unsolved or unexplored issues along with future perspectives on plant formins are proposed and discussed.
Actins ; Formins ; Microfilament Proteins ; Plant Cells ; Plant Development ; Plants