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Abstract 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.

Abstract Background Helicobacter pylori (H. pylori) is the predominant etiological agent of gastritis and disrupts the integrity of the gastric mucosal barrier through various pathogenic mechanisms. After H. pylori invades the gastric mucosa, it interacts with immune cells in the lamina propria. Macrophages are central players in the inflammatory response, and H. pylori stimulates them to secrete a variety of inflammatory factors, leading to the chronic damage of the gastric mucosa. Therefore, the study aims to explore the mechanism of gastric mucosal injury caused by inflammatory factors secreted by macrophages, which may provide a new mechanism for the development of H. pylori-related gastritis. Methods The expression and secretion of CCL3 from H. pylori infected macrophages were detected by RT-qPCR, Western blot and ELISA. The effect of H. pylori-infected macrophage culture medium and CCL3 on gastric epithelial cells tight junctions were analyzed by Western blot, immunofluorescence and transepithelial electrical resistance. EdU and apoptotic flow cytometry assays were used to detect cell proliferation and apoptosis levels. Dual-luciferase reporter assays and chromatin immunoprecipitation assays were used to study CCL3 transcription factors. Finally, gastric mucosal tissue inflammation and CCL3 expression were analyzed by hematoxylin and eosin staining and immunohistochemistry. Results After H. pylori infection, CCL3 expressed and secreted from macrophages were increased. H. pylori-infected macrophage culture medium and CCL3 disrupted gastric epithelial cells tight junctions, while CCL3 neutralizing antibody and receptor inhibitor of CCL3 improved the disruption of tight junctions between cells. In addition, H. pylori-infected macrophage culture medium and CCL3 recombinant proteins stimulated P38 phosphorylation, and P38 phosphorylation inhibitor improved the disruption of tight junctions between cells. Besides, it was identified that STAT1 was a transcription factor of CCL3 and H. pylori stimulated macrophage to secret CCL3 through the JAK1-STAT1 pathway. Finally, after mice were injected with murine CCL3 recombinant protein, the gastric mucosal injury and inflammation were aggravated, and the phosphorylation level of P38 was increased. Conclusions In summary, our findings demonstrate that H. pylori infection stimulates macrophages to secrete CCL3 via the JAK1-STAT1 pathway. Subsequently, CCL3 damages gastric epithelial tight junctions through the phosphorylation of P38. This may be a novel mechanism of gastric mucosal injury in H. pylori-associated gastritis.

Abstract Background Talar malignant tumor is extremely rare. Currently, there are several alternative management options for talus malignant tumor including below-knee amputation, tibio-calcaneal arthrodesis, and homogenous bone transplant while their shortcomings limited the clinical application. Three-dimensional (3D) printed total talus prosthesis in talus lesion was reported as a useful method to reconstruct talus, however, most researches are case reports and its clinical effect remains unclear. Therefore, the current study was to explore the application of 3D printed custom-made modular prosthesis in talus malignant tumor. Methods We retrospectively analyzed the patients who received the 3D printed custom-made modular prosthesis treatment due to talus malignant tumor in our hospital from February 2016 to December 2021. The patient's clinical data such as oncology outcome, operation time, and volume of blood loss were recorded. The limb function was evaluated with the Musculoskeletal Tumor Society 93 (MSTS-93) score, The American Orthopedic Foot and Ankle Society (AOFAS) score; the ankle joint ranges of motion as well as the leg length discrepancy were evaluated. Plain radiography and Tomosynthesis-Shimadzu Metal Artefact Reduction Technology (T-SMART) were used to evaluate the position of prosthesis and the osseointegration. Postoperative complications were recorded. Results The average patients’ age and the follow-up period were respectively 31.5 ± 13.1 years; and 54.8 months (range 26–72). The medium operation time was 2.4 ± 0.5 h; the intraoperative blood loss was 131.7 ± 121.4 ml. The mean MSTS-93 and AOFAS score was 26.8 and 88.5 respectively. The average plantar flexion, dorsiflexion, varus, and valgus were 32.5, 9.2, 10.8, and 5.8 degree respectively. One patient had delayed postoperative wound healing. There was no leg length discrepancy observed in any patient and good osseointegration was observed on the interface between the bone and talus prosthesis in all subjects. Conclusion The modular structure of the prosthesis developed in this study seems to be convenient for prosthesis implantation and screws distribution. And the combination of solid and porous structure improves the initial stability and promotes bone integration. Therefore, 3D printed custom-made modular talus prosthesis could be an alternative option for talus reconstruction in talus malignant tumor patients.

Abstract Background Debates persist over optimal pelvic girdle reconstruction after acetabular tumor resection, with surgeons grappling between modular and 3D-printed hemipelvic endoprostheses. We hypothesize superior outcomes with 3D-printed versions, yet scarce comparative research exists. This study fills the gap, examining biomechanics and clinical results retrospectively. Methods From February 2017 to June 2021, we retrospectively assessed 32 patients undergoing en bloc resection for malignant periacetabular tumors at a single institution. Primary outcome: limb function. Secondary outcomes: implant precision, hip joint rotation center restoration, prosthesis-bone osteointegration, and complications. Biomechanical characteristics were evaluated through finite element analysis on pelvic defect models. Results In the 3D-printed group, stress distribution mirrored a normal pelvis, contrasting the modular group with elevated overall stress, unstable transitions, and higher stress peaks. The 3D-printed group exhibited superior functional scores (MSTS: 24.3 ± 1.8 vs. 21.8 ± 2.0, p

Abstract Objective This study aims to biomimetic design a new 3D-printed lattice hemipelvis prosthesis and evaluate its clinical efficiency for pelvic reconstruction following tumor resection, focusing on feasibility, osseointegration, and patient outcomes. Methods From May 2020 to October 2021, twelve patients with pelvic tumors underwent tumor resection and subsequently received 3D-printed lattice hemipelvis prostheses for pelvic reconstruction. The prosthesis was strategically incorporated with lattice structures and solid to optimize mechanical performance and osseointegration. The pore size and porosity were analyzed. Patient outcomes were assessed through a combination of clinical and radiological evaluations. Results Multiple pore sizes were observed in irregular porous structures, with a wide distribution range (approximately 300–900 μm). The average follow-up of 34.7 months, ranging 26 from to 43 months. One patient with Ewing sarcoma died of pulmonary metastasis 33 months after surgery while others were alive at the last follow-up. Postoperative radiographs showed that the prosthesis’s position was consistent with the preoperative planning. T-SMART images showed that the host bone was in close and tight contact with the prosthesis with no gaps at the interface. The average MSTS score was 21 at the last follow-up, ranging from 18 to 24. There was no complication requiring revision surgery or removal of the 3D-printed hemipelvis prosthesis, such as infection, screw breakage, and prosthesis loosening. Conclusion The newly designed 3D-printed lattice hemipelvis prosthesis created multiple pore sizes with a wide distribution range and resulted in good osteointegration and favorable limb function.

Abstract Background The impact of antidepressants on Inflammatory bowel diseases (IBD) has been extensively studied. However, the biological effects and molecular mechanisms of antidepressants in alleviating colitis remain unclear. Methods We systematically assessed how antidepressants (fluoxetine, fluvoxamine and venlafaxine) affected IBD and chose fluoxetine, the most effective one, for mechanism studies. We treated the C56BL/6 mice of the IBD model with fluoxetine and their controls. We initially assessed the severity of intestinal inflammation in mice by body weight loss, disease Activity Index scores and the length of the colon. The H&E staining and immunohistochemical staining of MUC2 of colon sections were performed to observe the pathological changes. RT-qPCR and western blot were conducted to assess the expression level of the barrier and inflammation-associated genes. Then, single-cell RNA sequencing was performed on mouse intestinal mucosa. Seurat was used to visualize the data. Uniform Manifold Approximation and Projection (UMAP) was used to perform the dimensionality reduction. Cell Chat package was used to perform cell–cell communication analysis. Monocle was used to conduct developmental pseudotime analysis. Last, RT-qPCR, western blot and immunofluorescence staining were conducted to test the phenomenon discovered by single-cell RNA sequencing in vitro. Results We found that fluoxetine treatment significantly alleviated colon inflammation. Notably, single-cell RNA sequencing analysis revealed that fluoxetine affected the distribution of different cell clusters, cell–cell communication and KEGG pathway enrichment. Under the treatment of fluoxetine, enterocytes, Goblet cells and stem cells became the dominating cells. The pseudotime analysis showed that there was a trend for M1 macrophages to differentiate into M2 macrophages. Lastly, we tested this phenomenon in vitro, which exhibited anti-inflammatory effects on enterocytes. Conclusions Fluoxetine exhibited anti-inflammatory effects on intestinal mucosa via remodeling of the intestinal cells and macrophages, which reveals that fluoxetine is a promising therapeutic drug for the treatment of IBD and psychiatric comorbidities.

Abstract 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

Abstract Background Anemia is a common health problem in the elderly. Preoperative anemia is a risk factor for postoperative outcomes in the elderly for hip fracture. The objective of the study was to explore the relationship between preoperative moderate to severe anemia and postoperative morbidity and mortality in hip fracture patients over 80 years old. Methods We performed a retrospective cohort study exploring preoperative moderate to severe anemia and postoperative morbidity and mortality. Patients over 80 years old undergoing hip fracture surgery were included in the study. Data were collected for major adverse cardiac and cerebral events (MACCE), postoperative pulmonary complications (PPCs), in-hospital mortality, delirium, gastrointestinal complication, deep venous thrombus (DVT), acute renal failure, ICU admission, and perioperative transfusion > 2 units rate. Results A total of 912 eligible patients were included for unmatched cohort analysis, and 512 patients were included for matched cohort analysis after propensity score matching. Baseline characteristics between the normal to mild anemia and moderate to severe anemia groups were significantly different. More patients in the moderate to severe cohort had a higher ASA classification grade III and female ratio. Patients in the moderate and severe anemia cohorts had more MACCE (unadjusted: odds ratio [OR] 1.968, 96% CI 1.090–3.555, P 0.023; adjusted: OR 1.929, 95% CI 1.014–3.668, P 0.045) and PPCs (unadjusted: OR 2.616, 95% CI 1.442–4.748, P 0.001; adjusted: OR 2.352, 95% CI 1.225–4.516, P 0.010) than patients with normal or mild anemia. However, the transfusion > 2 units rate was not significantly different between the two cohorts (unadjusted: OR 0.967, 95% CI 0.737–1.270, P 0.811; adjusted: OR 0.941, 95% CI 0.693–1.278, P 0.697). The in-hospital mortality, delirium rate, gastrointestinal complication, ICU admission, and DVT were similar. However, the in-hospital mortality was much higher (3.6%, 21/591 vs 1.6%, 5/321) in the moderate to severe anemia cohort. Furthermore, after propensity score-matched analysis, MACCE and PPCs were also significantly increased in the moderate to severe anemia cohort (OR 2.196 & 3.171, 95% CI 1.0794.470 & 1.563–6.436, P 0.027 & 0.001), which were in accordance with the unadjusted and adjusted results in the unmatched cohorts. Conclusions Moderate to severe preoperative anemia (

Abstract Background This study reports our experience in the treatment of aggressive pelvic GCT through wide resection assisted with patient-specific bone-cutting guides (PSBCGs) and subsequent reconstruction with 3D-printed personalized implants (3DPIs), aiming to present the operative technique of this method and evaluate its clinical efficacy. Methods We retrospectively analyzed seven patients who underwent wide resection of pelvic GCT followed by reconstruction with 3DPIs from August 2019 to February 2021. There were two males and five females, with a mean age of 43 years. PSBCGs and 3DPIs were prepared using 3D-printing technology. The operational outcomes, local recurrence, radiological results, and any associated complications of this technique were assessed. And the functional outcomes were assessed according to the Musculoskeletal Tumor Society (MSTS) 93 functional score. Results The mean follow-up time was 35.3 months (range 28–45 months). There was no intraoperative complication. Negative surgical margins were achieved in all patients. Postoperative pelvic radiographs showed that 3DPIs matched the shape and size of the bone defect. The anterior–posterior, inlet, and outlet pelvic radiograph demonstrated precise reconstruction consistent with the surgical planning. In addition, tomosynthesis‐Shimadzu metal artifact reduction technology (T-SMART) showed good osseointegration at an average of three months after surgery (range 2–4 months). There was no local recurrence or tumor metastasis. The average MSTS score was 24.4 (range 23–27) at the last follow-up. Delayed wound healing was observed in one patient, and the wounds healed after debridement. Prosthesis-related complications were not detected during the follow-up, such as aseptic loosening or structure failure. Conclusions The treatment of aggressive pelvic GCTs through wide resection assisted with PSBCGs and subsequent reconstruction with 3DPIs is a feasible method, which provides good clinical results and reasonable functional outcomes.

Abstract Background Joint-salvage surgery has been proposed in children with metaphysis malignancy of the distal femur. However, there is still some drawbacks regarding to the surgical technique and endoprosthetic design. In this study, we evaluated the efficacy of a joint-sparing surgical technique for the distal femur in pediatric patients using intraoperative physeal distraction and reconstruction of a 3D-printed endoprosthesis. Methods We retrospectively analyzed pediatric patients with distal femoral malignancy who underwent intraoperative physeal distraction and 3D-printed endoprosthetic reconstruction. Clinically, we evaluated functional outcomes using the 1993 version of the Musculoskeletal Tumor Society (MSTS-93) score pre- and post-operation. Complications were also recorded. Results Seven children with a median age of 11 years (range 8–15 years) were finally included in our study. The median follow-up time was 30 months (range 27–59 months). The median postoperative functional MSTS-93 score was increased compared with the preoperative scores. The bone-implant interface showed good osseointegration. One patient developed deep infection and another had lung metastasis after surgery. Endoprosthetic complications were not observed. Conclusion We recommended that joint-preserving surgery with intraoperative physeal distraction and a 3D-printed endoprosthesis for reconstruction as an option for malignancies of the distal femur in selected pediatric patients.

Abstract Background Revision of cemented distal femoral replacement (DFR) due to aseptic loosening is challenging because of the resultant femoral bone loss. This paper aims to examine the outcomes of three-dimensional (3D) design custom-made uncemented stems for revision. Methods Between January 2014 and December 2020, 17 patients received 3D design uncemented stems for revision of loosed cemented DFR. The femoral bone loss was classified into four Grades, and four types of uncemented stems were designed correspondingly. The revision stems were custom-made for each patient by measuring the diameter of the medullary cavity and the anterior curvature of the femur. Results The patient counts with their corresponding Grades of femoral bone loss were as follows: Grade I, 8 patients; Grade II, 5 patients; Grade III, 3 patients; and Grade IV, 1 patient. During the mean follow-up of 80 months, no revision failure was detected. The postoperative radiographic showed that the stem matched the femoral anterior curvature well. The femoral bone defect was completely filled by the 3D design stem in 10 of the 17 cases postoperatively. In the remaining cases, the persistent peri-stem defect was filled or partially restored during the follow-up. Conclusion 3D design custom-made uncemented stem created precise, stable, and durable fixation and provided satisfactory clinical outcomes, which seems to be a viable method for cemented DFR revision.

Abstract Background Large malignant bone tumors and revision limb salvage procedures often result in massive bone loss, leaving a short residual bone segment that cannot accommodate a standard stem for endoprosthesis fixation. Three-dimensional-printed (3DP) short stem with porous structure seems to be an alternative for short-segment fixation. This retrospective study aims to evaluate surgical outcomes, radiographical results, limb functions, and complications of using 3DP porous short stems in massive endoprosthesis replacement. Methods Between July 2018 to February 2021, 12 patients with massive bone loss undergoing reconstruction with custom-made, short-stemmed massive endoprostheses were identified. Endoprosthesis replacement involved the proximal femur (n = 4), distal femur (n = 1), proximal humerus (n = 4), distal humerus (n = 1), and proximal radius (n = 2). Results The mean percentage of resected bone was 72.4% of the whole length of the bone, ranging from 58.4 to 88.5%. The mean length of 3DP porous short stems was 6.3 cm. The median follow-up was 38 months (range, 22–58 months). The mean MSTS score was 89%, ranging from 77% to 93%. Radiographical assessment results showed bone in-growth to the porous structure in 11 patients, and the implants were well osseointegrated. Breakage of the 3DP porous short stem occurred in one patient intraoperatively. The patient developed aseptic loosening (Type 2) four-month after surgery and underwent revision with a plate applied to assist fixation. The implant survivorship was 91.7% at 2 years. No other complications were detected, such as soft-tissue failures, structural failures, infection, or tumor progression. Conclusions 3DP custom-made short stem with porous structure is a viable method for fixation of the massive endoprosthesis in the short segment after tumor resection, with satisfactory limb function, great endoprosthetic stability, and low complication rates.

Abstract Background Treatment of methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium (Ti) implants. There is a need to explore more effective approaches for the treatment of MRSA biofilm infections. Methods Herein, an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles (PDA), nitric oxide (NO) release donor sodium nitroprusside (SNP) and osteogenic growth peptide (OGP) onto Ti implants, denoted as Ti-PDA@SNP-OGP. The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy, X-ray photoelectron spectroscope, water contact angle, photothermal property and NO release behavior. The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe, 1-N-phenylnaphthylamine assay, adenosine triphosphate intensity, o-nitrophenyl-β-d-galactopyranoside hydrolysis activity, bicinchoninic acid leakage. Fluorescence staining, assays for alkaline phosphatase activity, collagen secretion and extracellular matrix mineralization, quantitative real‑time reverse transcription‑polymerase chain reaction, and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells (MSCs), RAW264.7 cells and their co-culture system. Giemsa staining, ELISA, micro-CT, hematoxylin and eosin, Masson’s trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms, inhibition of inflammatory response, and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo. Results Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light irradiation, and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species (ROS)-mediated oxidative stress, destroying bacterial membrane integrity and causing leakage of intracellular components (P

Abstract Backgrounds Kidney stone also known as urolithiasis or nephrolithiasis, is one of the oldest diseases known to medicine, however, the gene expression changes and related kidney injury remains unclear. Methods A calculi rat model was developed via ethylene glycol– and ammonium chloride–induction. Integrated proteomic and transcriptomic analysis was performed to characterize the distinct gene expression profiles in the kidney of calculi rat. Differential expressed genes (DEGs) were sub-clustered into distinct groups according to the consistency of transcriptome and proteome. Gene Ontology and KEGG pathway enrichment was performed to analyze the functions of each sub-group of DEGs. Immunohistochemistry was performed to validated the expression of identified proteins. Results Five thousand eight hundred ninety-seven genes were quantified at both transcriptome and proteome levels, and six distinct gene clusters were identified, of which 14 genes were consistently dysregulated. Functional enrichment analysis showed that the calculi rat kidney was increased expression of injured & apoptotic markers and immune-molecules, and decreased expression of solute carriers & transporters and many metabolic related factors. Conclusions The present proteotranscriptomic study provided a data resource and new insights for better understanding of the pathogenesis of nephrolithiasis, will hopefully facilitate the future development of new strategies for the recurrence prevention and treatment in patients with kidney stone disease.

Abstract Cuproptosis is a newly discovered type of cell death triggered by copper accumulation. Here we exhibited the genetic profiles of 10 cuproptosis-associated genes (CuAGs) across 21 cancer types. Only 8.0% (627/7839) of tumors possessed at least 1 mutation on CuAGs, while the copy number amplifications or deletions on the alleles of CuAGs were ubiquitous. Generally, the expression of CuAGs showed heterogeneity across cancer types and the expression of CuAGs showed different correlations with MSI, TMB, immune and stromal features in different cancer types. Therefore, CuAGs were ubiquitously and heterogeneously dysregulated in pan-cancer. With a Non-negative Matrix Factorization method, we divided patients of each cancer type into cuproptosis-based subtypes, which showed a close but heterogeneous correlation with different biological and clinical features. Accordingly, we summarized all cancer types into four categories. The cancers in which cuproptosis subtypes correlated with MSI and TMB were annotated as Genomic disturbed. Those correlated with stromal scores were categorized as Stromal remolded. The others only associated with immune infiltration were labeled as Immune inhibited. A minor fraction of cancers not correlated with any biological indicators were marked as Cuproptosis inert. Together, we provided a pan-cancer overview of cuproptosis markers which revealed biologically and clinically relevant cancer subtypes in different cancers.

Abstract Background Neoadjuvant radiotherapy (NRT) for resectable retroperitoneal sarcoma (RPS) has been shown to be systematically feasible. Whether NRT has equivalent or better clinical effects compared to surgery alone for RPS patients remains controversial. Methods We performed a systematic literature search of PubMed, Web of Science, Embase, ASCO Abstracts, and Cochrane library databases for studies in humans with defined search terms. Articles were independently assessed by 2 reviewers, and only randomized controlled trials and cohort studies were included. The hazard ratios (HRs) of overall survival (OS), recurrence-free survival (RFS), and local recurrence (LR) were extracted from included studies. Heterogeneity among study-specific HRs was assessed by the Q statistic and I2 statistic. Overall HR was assessed by random-effects or fixed-effects models. Publication bias was tested by Begg’s tests, and the quality of each study was assessed with the Newcastle Ottawa Scale. Results A total of 12 eligible studies with 7778 resectable RPS patients were finally included in this study. The pooled analysis revealed the distinct advantages of NRT as compared to surgery alone, including longer OS (HR = 0.81, P

Abstract 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.

Abstract Background Surgical transepicondylar axis (sTEA) is frequently used for positioning of femoral component rotation in total knee arthroplasty (TKA). Previous studies showed that intraoperative identification of sTEA was not reliable. While surgeons or engineers need to identify sTEA with three-dimensional (3D) computer-aid techniques pre- or intraoperatively, the reproducibility of sTEA identification on preoperative 3D images has not been explored yet. This study aimed to investigate the reproducibility of identifying sTEA in preoperative planning based on computed tomography (CT). Methods Fifty-nine consecutive patients (60 knees involved) who received TKA in our center from April 2019 to June 2019 were included in this study. Six experienced TKA surgeons identified sTEA three times on 3D model established on the basis of knee CT data. The projection angle of each sTEA and the posterior condyle axis on the transverse plane were measured and analyzed. Results The overall intra-observer reproducibility was moderate. The median intra-observer variation was 1.27°, with a maximum being up to 14.07°. The median inter-observer variation was 1.24°, and the maximum was 11.47°. The overall intra-class correlation coefficient (ICC) for inter-observer was 0.528 (95% CI 0.417, 0.643). Conclusion The identification of sTEA on a 3D model established on the basis of knee CT data may not be reliable. Combined with the previous cadaveric and surgical studies, caution should be exercised in determining femoral component rotation by referencing sTEA both preoperatively and intraoperatively. Level of evidence III

Abstract 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.

Abstract Background Hip-preserved reconstruction for patients with ultrashort proximal femur segments following extensive femoral diaphyseal tumor resection is a formidable undertaking. A customized intercalary prosthesis with a rhino horn-designed uncemented stem was developed for the reconstruction of these extensive skeletal defects. Methods This study was designed to analyze and compare the differences in the biomechanical behavior between the normal femur and the femur with diaphyseal defects reconstructed by an intercalary prosthesis with different stems. The biomechanical behavior under physiological loading conditions is analyzed using the healthy femur as the reference. Five three-dimensional finite element models (healthy, customized intercalary prosthesis with four different stems implemented, respectively) were developed, together with a clinical follow-up of 12 patients who underwent intercalary femoral replacement. Results The biomechanical results showed that normal-like stress and displacement distribution patterns were observed in the remaining proximal femur segments after reconstructions with the rhino horn-designed uncemented stems, compared with the straight stem. Stem A showed better biomechanical performance, whereas the fixation system with Stem B was relatively unstable. The clinical results were consistent with the FEA results. After a mean follow-up period of 32.33 ± 9.12 months, osteointegration and satisfactory clinical outcomes were observed in all patients. Aseptic loosening (asymptomatic) occurred in one patient reconstructed by Stem B; there were no other postoperative complications in the remaining 11 patients. Conclusion The rhino horn-designed uncemented stem is outstanding in precise shape matching and osseointegration. This novel prosthesis design may be beneficial in decreasing the risk of mechanical failure and aseptic loosening, especially when Stem A is used. Therefore, the customized intercalary prosthesis with this rhino horn-designed uncemented stem might be a reasonable alternative for the reconstruction of SSPF following extensive tumor resection.

Abstract The current diagnosis and treatment of sarcoma continue to show limited timeliness and efficacy. In order to enable the early detection and management of sarcoma, increasing attentions have been given to the tumor microenvironment (TME). TME is a dynamic network composed of multiple cells, extracellular matrix, vasculature, and exosomes. Exosomes are nano-sized extracellular vesicles derived from various cells in the TME. The major function of exosomes is to promote cancer progress and metastasis through mediating bidirectional cellular communications between sarcoma cells and TME cells. Due to the content specificity, cell tropism, and bioavailability, exosomes have been regarded as promising diagnostic and prognostic biomarkers, and therapeutic vehicles for sarcoma. This review summarizes recent studies on the roles of exosomes in TME of sarcoma, and explores the emerging clinical applications.

Abstract Background Retroperitoneal liposarcoma (RPLS) is a specific soft tissue sarcoma with a high recurrence rate. The short isoform of transient receptor potential cation channel subfamily M member 2 (TRPM2-S) plays an important role in the regulation of reactive oxygen species (ROS). However, the association between TRPM2-S and RPLS and its underlying mechanisms remains unclear. Methods The expression of both TRPM2-S and TRPM2-L in RPLS tissues was verified by kimmunohistochemistry (IHC). The regulation on Ca2+ influx by TRPM2-S was evaluated by Fluo-4 AM staining. The effect of TRPM2-S on cell proliferation and apoptosis was tested by 5-Ethynyl-2′-deoxyuridine (EdU) staining and Flow cytometry respectively. The level of cellular ROS was assessed by the DCFH-DA probe. Different concentrations of H2O2 were used to provide oxidative stress on RPLS cells. The underlying mechanisms were further explored by Western blotting. Results The IHC assays showed that TRPM2-S, but not TRPM2-L, was prognostic in RPLS. Low TRPM2-S level was associated with poor disease-free survival (DFS). Calcium influx signal intensity was significantly decreased under TRPM2-S overexpression, which resulted in a decrease in the levels of FOXO3a and PTEN. Correspondingly, the levels of pERK, pAKT, pP65, pGSK-3β, Bcl-2, and β-catenin were upregulated, and cellular ROS was gently increased under TRPM2-S overexpression. Moreover, TRPM2-S slightly promoted cell proliferation and inhibited apoptosis of RPLS cell lines under normoxia, but largely increased apoptosis rates under oxidative stress. The cleaved caspase3 was significantly upregulated by TRPM2-S overexpression under oxidative stress. N-Acetyl-l-cysteine (NAC), a small molecule antioxidant, could largely rescue RPLS cells from the apoptosis induced by H2O2. Conclusion TRPM2-S exerts Janus-faced effects in RPLS by increasing the ROS levels via inhibition on FOXO3a, which promotes cell proliferation under normoxia but induces apoptosis under oxidative stress. Video abstract

Abstract Background Pulmonary fibrosis is a progressive and usually lethal pulmonary disease. Despite considerable research efforts, no effective therapeutic strategy for pulmonary fibrosis has been developed. NecroX-5 has been reported to possess anti-inflammatory, anti-oxidative and anti-tumor activities. In the present study, we aimed to determine whether NecroX-5 exhibits antifibrotic property in bleomycin (BLM)-induced pulmonary fibrosis. Results We found that pre-treatment with NecroX-5 alleviated inflammatory response, reduced oxidative stress, inhibited epithelial–mesenchymal transition (EMT), and ameliorated pulmonary fibrosis in vivo and in vitro. Our data further indicated that NecroX-5 substantially reduced activation of NLRP3 inflammasome and TGF-β1/Smad2/3 signaling in vivo and in vitro. Additionally, NLRP3 overexpression significantly reversed the protective effects of NecroX-5 in lung epithelial cells exposed to BLM. Conclusions Overall, our results demonstrate the potent antifibrotic properties of NecroX-5 and its therapeutic potential for pulmonary fibrosis.

Abstract Aims Investigate the effect and mechanism of COX-2 on viability, intestinal metaplasia, and atypia in human esophageal squamous and Barrett esophageal cell lines. Methods Human esophageal squamous and Barrett esophageal cell lines were transfected with a COX-2 expression vector and a COX-2 siRNA, and then were treated with acid, bile salts, and a mixture of both. Cell viability, the expression of COX-2, NF-κB(p65), CDX-2, MUC2, c-myb, and BMP-4, and the morphology and microstructure of cells were then observed. Results The viability of COX-2 overexpressed cells was significantly higher than that of control cells, while the viability of COX-2 siRNA-treated cells was significantly lower than that of control cells. Intestinal metaplasia and atypia were observed in cells overexpressing COX-2. Acid, bile salts, and their mixture inhibited the viability of these two cell lines, but the inhibitory effect of the mixture was stronger than a single treatment in either. SiRNA mediated knockdown of COX-2 strengthened the antiproliferative effects of the mixture on HET-1A and BAR-T cells. The expression of p-p65, CDX-2, and BMP-4 was positively correlated with COX-2 expression, while the expression levels of p65, MUC2, and c-myb remained unchanged. Conclusion COX-2 may influence the viability, atypia, and intestinal metaplasia of human esophageal cells and Barrett esophageal cells. Activation of the p-p65, CDX-2, and BMP-4 signaling pathways by COX-2 may be part of this mechanism.

Abstract Background The most common reconstruction method for bone defects caused by giant cell tumor of bone (GCTB) is cement packing combined with subchondral bone grafting and extra fixation. However, this method has several limitations involving bone cement and bone graft, which may lead to poor prognosis and joint function. A titanium-based 3D-printed strut-type prosthesis, featured with excellent biocompatibility and osseointegration ability, was developed for this bone defect in our institution. The goal of this study is to comparatively analyze the biomechanical performance of reconstruction methods aimed at the identification of better operative strategy. Methods Four different 3D finite element models were created. Model #1: Normal femur; Model #2: Femur with tumorous cavity bone defects in the distal femur; Model #3: Cavity bone defects reconstructed by cement packing combined with subchondral bone grafting and extra fixation; Model #4: Cavity bone defects reconstructed by 3D-printed strut-type prosthesis combined with subchondral bone grafting. The femoral muscle multiple forces were applied to analyze the mechanical difference among these models by finite element analysis. Results Optimal stress and displacement distribution were observed in the normal femur. Both reconstruction methods could provide good initial stability and mechanical support. Stress distributed unevenly on the femur repaired by cement packing combined with subchondral bone grafting and extra fixation, and obvious stress concentration was found around the articular surface of this femur. However, the femur repaired by 3D-printed strut-type prosthetic reconstruction showed better performance both in displacement and stress distribution, particularly in terms of the protection of articular surface and subchondral bone. Conclusions 3D-printed strut-type prosthesis is outstanding in precise shape matching and better osseointegration. Compared to cement packing and extra fixation, it can provide the almost same support and fixation stiffness, but better biomechanical performance and protection of subchondral bone and articular cartilage. Therefore, 3D-printed strut-type prosthetic reconstruction combined with subchondral bone grafting may be evaluated as an alternative for the treatment of GCTBs in distal femur.

Abstract Background Pelvic organ prolapse (POP) is seen in up to 30–70% of women presenting for routine gynecology care and 10% of women suffering from bothersome POP symptoms. Vaginal childbirth is one of the most prominent contributing factors for POP. Pelvic muscle training (PFMT) is considered effective to improve mild to moderate POP symptoms. In addition, higher-intensity, supervised PFMT aided by biofeedback and electrical stimulation may confer greater benefit. However, the long-term efficacy of the PFMT combined with electromyography biofeedback is unknown, which indicates the need for further evidence. Methods This multicenter randomized controlled trial compares the effectiveness and cost-effectiveness of conventional PFMT versus biofeedback-mediated PFMT plus neuromuscular electrical stimulation (NMES) for postpartum symptomatic POP women. The primary outcome is the proportion of patients with the improvement of at least one POP-Q stage at 36 months after randomization. The primary economic outcome measure is incremental cost per quality-adjusted life year at 36 months. Two hundred seventy-four women from four outpatient medical centers are randomized and followed up with pelvic floor examination, questionnaires, and pelvic ultrasonography imaging. All participants are arranged for three appointments over 12 weeks. NMES and electromyography biofeedback via intravaginal probe are added to PFMT for participants in the biofeedback-mediated PFMT group. Group allocation could not be blinded from participants and healthcare staff that deliver intervention but remain masked from medical staff that carry out PFM assessment. An intention-to-treat analysis of the primary outcome will estimate the difference of the proportion of POP-Q stage improvement between the trial groups right after the intervention, and during the follow-up until 36 months, using the chi-square test and multilevel mixed models respectively. A logistic regression analysis was used for adjusting for important baseline variables that are unbalanced. Discussion The trial results will provide evidence of the effectiveness of electromyography biofeedback-mediated PFMT in improving women’s POP-Q staging, quality of life, and cost-effectiveness. Trial registration CCTR Registry ChiCTR210002171917 . Registered on March 6, 2019

Abstract Background Bioassessment and biomonitoring of meat products are aimed at identifying and quantifying adulterants and contaminants, such as meat from unexpected sources and microbes. Several methods for determining the biological composition of mixed samples have been used, including metabarcoding, metagenomics and mitochondrial metagenomics. In this study, we aimed to develop a method based on next-generation DNA sequencing to estimate samples that might contain meat from 15 mammalian and avian species that are commonly related to meat bioassessment and biomonitoring. Results In this project, we found the meat composition from 15 species could not be identified with the metabarcoding approach because of the lack of universal primers or insufficient discrimination power. Consequently, we developed and evaluated a meat mitochondrial metagenomics (3MG) method. The 3MG method has four steps: (1) extraction of sequencing reads from mitochondrial genomes (mitogenomes); (2) assembly of mitogenomes; (3) mapping of mitochondrial reads to the assembled mitogenomes; and (4) biomass estimation based on the number of uniquely mapped reads. The method was implemented in a python script called 3MG. The analysis of simulated datasets showed that the method can determine contaminant composition at a proportion of 2% and the relative error was

Abstract 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.

Abstract Background Adjuvant therapy is a promising treatment to improve the prognosis of cancer patients, however, the evidence base driving recommendations for adjuvant radiotherapy (ART) or chemotherapy (ACT) in retroperitoneal sarcomas (RPS) primarily hinges on observational data. The aim of this study was to evaluate the effectiveness of adjuvant therapy in the management of RPS patients. Methods We searched PubMed, Web of Science, Embase, ASCO Abstracts, and Cochrane Library for comparative studies (until December 2020) of adjuvant therapy versus surgery alone. Data on the following endpoints were evaluated: overall survival (OS), local recurrence (LR), recurrence-free survival (RFS), and metastasis-free survival (MFS). Data were summarized as hazard ratios (HR) with 95% confidence intervals (CI). Risk of bias of studies was assessed with Begg’s and Egger’s tests. Results A total of 15 trials were eligible, including 9281 adjuvant therapy and 21,583 surgery alone cases (20 studies for OS, six studies for RFS, two studies for LR, and two studies for MFS). Meta-analysis showed that ART was associated with distinct advantages as compared to surgery alone, including a longer OS (HR = 0.80, P

Abstract Background Long-lasting reconstruction after extensive resection involving peri-knee metaphysis is a challenging problem in orthopedic oncology. Various reconstruction methods have been proposed, but they are characterized by a high complication rate. The purposes of this study were to (1) assess osseointegration at the bone implant interface and correlated incidence of aseptic loosening; (2) identify complications including infection, endoprosthesis fracture, periprosthetic fracture, leg length discrepancy, and wound healing problem in this case series; and (3) evaluate the short-term function of the patient who received this personalized reconstruction system. Methods Between September 2016 and June 2018, our center treated 15 patients with malignancies arising in the femur or tibia shaft using endoprosthesis with a 3D-printed custom-made stem. Osseointegration and aseptic loosening were assessed with digital tomosynthesis. Complications were recorded by reviewing the patients’ records. The function was evaluated with the 1993 version of the Musculoskeletal Tumor Society (MSTS-93) score at a median of 42 (range, 34 to 54) months after reconstruction. Results One patient who experienced early aseptic loosening was managed with immobilization and bisphosphonates infusion. All implants were well osseointegrated at the final follow-up examination. There are two periprosthetic fractures intraoperatively. The wire was applied to assist fixation, and the fracture healed at the latest follow-up. Two patients experienced significant leg length discrepancies. The median MSTS-93 score was 26 (range, 23 to 30). Conclusions A 3D-printed custom-made ultra-short stem with a porous structure provides acceptable early outcomes in patients who received peri-knee metaphyseal reconstruction. With detailed preoperative design and precise intraoperative techniques, the reasonable initial stability benefits osseointegration to osteoconductive porous titanium, and therefore ensures short- and possibly long-term durability. Personalized adaptive endoprosthesis, careful intraoperative operation, and strict follow-up management enable effective prevention and treatment of complications. The functional results in our series were acceptable thanks to reliable fixation in the bone-endoprosthesis interface and an individualized rehabilitation program. These positive results indicate this device series can be a feasible alternative for critical bone defect reconstruction. Nevertheless, longer follow-up is required to determine whether this technique is superior to other forms of fixation.

Abstract Background The formation of a uterine artery pseudoaneurysm is rare and isolated cases have been reported in the existing literature following caesarean sections, curettages and cone biopsies. There has been no report of pseudoaneurysm formation following a loop electrosurgical excision procedure. Vaginal bleeding could potentially be life threatening if this diagnosis is not considered following cervical instrumentation or surgery. Management options range from haemostatic sutures, image-guided embolisation to surgical repair. We report the diagnosis and management of a case of uterine artery pseudoaneurysm after a loop electrosurgical excision procedure. Case presentation A 37-year-old woman was diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) and underwent a therapeutic loop electrosurgical excision procedure. One month after the procedure, the patient presented to the emergency department with repeated episodes of sudden-onset heavy vaginal bleeding associated with hypotension and syncope. A computed tomography angiogram was performed, which demonstrated a pseudoaneurysm of the right uterine artery. Following the diagnosis, image-guided embolisation was performed successfully. Post-embolisation angiograms showed successful embolisation of the pseudoaneurysm and the patient had no further episodes of bleeding. Conclusions Loop electrosurgical excision procedures are generally safe but rarely, can be complicated by the formation of uterine artery pseudoaneurysms. The depth of the loop electrosurgical excision procedure and vascular anatomy should be considered to prevent such complications. A computed tomography angiogram appears to be ideal for diagnosis. Image-guided embolisation is safe and effective as a therapeutic measure, with minimal morbidity.

Abstract Background This study aims to investigate clinical significance of HMGB1 in neonatal patients with necrotizing enterocolitis (NEC). Methods This observational study enrolled a total of 106 stage II-III NEC neonatal patients, who were admitted in our hospital from March 2014 to March 2019. In addition, 99 suspected NEC patients and 200 healthy controls were included. The serum levels of HMGB1, I-FABP, and inflammatory factors CRP, IL-1β, IL-6 and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). Then, the demographic data and clinical characteristics of all patients were collected. Statistical analysis was conducted to determine the correlation between HMGB1 and the clinical characteristics. Results No significant difference was found in the basic characteristics of NEC patients and healthy controls, except for birth weight and gestational age. The expression levels of HMGB1, I-FABP, and inflammatory factors IL-1β, IL-6 and TNF-α were significantly higher in NEC patients, when compared to healthy controls. The serum levels of HMGB1, I-FABP, IL-1β and IL-6 markedly increased in stage II-III NEC patients, when compared to stage I NEC patients. The Pearson’s analysis revealed a positive correlation between HMGB1 and I-FABP, HMGB1 and IL-1β, and HMGB1 and IL-6. The ROC curve revealed that both HMGB1 and I-FABP can potentially be used as diagnostic factors for NEC. The logistic multivariate regression revealed that I-FABP, IL-1β and IL-6 are independent risk factors for mortality in neonatal NEC patients. Conclusions Serum HMGB1 levels are upregulated in neonatal NEC patients, and these are correlated with the patient’s prognosis.

Abstract Backgrounds Liver hepatocellular carcinoma (HCC) is one of the most malignant tumors, of which prognosis is unsatisfactory in most cases and metastatic of HCC often results in poor prognosis. In this study, we aimed to construct a metastasis- related mRNAs prognostic model to increase the accuracy of prediction of HCC prognosis. Methods Three hundred seventy-four HCC samples and 50 normal samples were downloaded from The Cancer Genome Atlas (TCGA) database, involving transcriptomic and clinical data. Metastatic-related genes were acquired from HCMBD website at the same time. Two hundred thirty-three samples were randomly divided into train dataset and test dataset with a proportion of 1:1 by using caret package in R. Kaplan-Meier method and univariate Cox regression analysis and lasso regression analysis were performed to obtain metastasis-related mRNAs which played significant roles in prognosis. Then, using multivariate Cox regression analysis, a prognostic prediction model was established. Transcriptome and clinical data were combined to construct a prognostic model and a nomogram for OS evaluation. Functional enrichment in high- and low-risk groups were also analyzed by GSEA. An entire set based on The International Cancer Genome Consortium(ICGC) database was also applied to verify the model. The expression levels of SLC2A1, CDCA8, ATG10 and HOXD9 are higher in tumor samples and lower in normal tissue samples. The expression of TPM1 in clinical sample tissues is just the opposite. Results One thousand eight hundred ninety-five metastasis-related mRNAs were screened and 6 mRNAs were associated with prognosis. The overall survival (OS)-related prognostic model based on 5 MRGs (TPM1,SLC2A1, CDCA8, ATG10 and HOXD9) was significantly stratified HCC patients into high- and low-risk groups. The AUC values of the 5-gene prognostic signature at 1 year, 2 years, and 3 years were 0.786,0.786 and 0.777. A risk score based on the signature was a significantly independent prognostic factor (HR = 1.434; 95%CI = 1.275–1.612; P

Abstract Introduction Healthy Beginnings is an established nurse-led early childhood obesity prevention program that promotes healthy infant feeding practices and active play in the early years of life. To improve engagement with culturally and linguistically diverse populations, the Healthy Beginnings program delivered by telephone was culturally adapted and implemented with Arabic- and Chinese-speaking mothers in Sydney, Australia. The cultural adaptation process has been published separately. In this article, we aimed to evaluate the feasibility of the culturally adapted program. Methods In 2018–2019, the culturally adapted Healthy Beginnings program was implemented with Arabic- and Chinese-speaking women recruited from antenatal clinics in Sydney. At four staged timepoints (from third trimester until 6 months of age), mothers were sent culturally adapted health promotion booklets and text messages and offered four support calls from bi-cultural child and family health nurses in Arabic and Chinese. A mixed methods evaluation included a) baseline and 6-month telephone surveys, followed by b) semi-structured follow-up interviews with a subset of participating mothers and program delivery staff. Main outcomes of this feasibility study were reach (recruitment and retention), intervention dose delivered (number of nurse support calls completed) and acceptability (appropriateness based on cognitive and emotional responses). Results At recruitment, 176 mothers were eligible and consented to participate. Of 163 mothers who completed the baseline survey, 95% completed the program (n = 8 withdrew) and 83% completed the 6-month survey (n = 70 Arabic- and n = 65 Chinese-speaking mothers). Most mothers (n = 127, 78%) completed at least one nurse support call. The qualitative analysis of follow-up interviews with 42 mothers (22 Arabic- and 20 Chinese-speaking mothers) and 10 program delivery staff highlighted the perceived value of the program and the positive role of bi-cultural nurses and in-language resources. Mothers who completed more nurse support calls generally expressed greater acceptability. Conclusions The culturally adapted Healthy Beginnings program was feasible to deliver and acceptable to Arabic- and Chinese-speaking mothers. Our results highlight the importance of in-language resources and individualised bi-cultural nurse support by telephone for supporting culturally and linguistically diverse migrant families with infant feeding and active play. These findings support the potential for program refinements and progression to an effectiveness trial.

Abstract Background The aims of this pilot study were (1) to assess the efficacy of 3D-printed custom-made hemipelvic endoprosthesis in restoring the natural location of acetabulum for normal bodyweight transmission; (2) to evaluate the short-term function of the revision with this endoprosthesis and (3) to identify short-term complications associated with the use of this endoprosthesis. Methods Between February 2017 and December 2017, seven patients received revision with 3D-printed custom-made hemipelvic endoprosthesis. The body weight moment arm (BWMA) and cup height discrepancy (CHD) after primary and revisional surgery were analyzed to assess acetabulum location with plain radiography. After a median follow-up duration of 29 months (range 24–34), the function was evaluated with the Musculoskeletal Tumor Society (MSTS-93) score and Harris hip score (HHS). Complications were recorded by chart review. Results The acetabulum locations were deemed reasonable, as evaluated by median BWMA (primary vs. revision, 10 cm vs. 10 cm) and median CHD (primary vs. revision, 10 mm vs. 8 mm). The median MSTS-93 score and HHS score were 21 (range 18–23) and 78 (range 75–82) after the revision. No short or mid-term complication was observed in the follow-up of this series. Conclusions Revision with 3D-printed custom-made hemipelvic endoprostheses benefited in reconstructing stable pelvic ring and natural bodyweight transmission for patients encountering the aseptic loosening and fracture of modular hemipelvic endoprosthesis. The revision surgery and appropriate rehabilitation program improved patients’ function to a median MSTS score of 22 and pain-free ambulation. The incidence of the complications was low via this individualized workflow.

Abstract Background Low temperature severely depresses the uptake, translocation from the root to the shoot, and metabolism of nitrate and ammonium in thermophilic plants such as cucumber (Cucumis sativus). Plant growth is inhibited accordingly. However, the availability of information on the effects of low temperature on nitrogen transport remains limited. Results Using non-invasive micro-test technology, the net nitrate (NO3 −) and ammonium (NH4 +) fluxes in the root hair zone and vascular bundles of the primary root, stem, petiole, midrib, lateral vein, and shoot tip of cucumber seedlings under normal temperature (NT; 26 °C) and low temperature (LT; 8 °C) treatment were analyzed. Under LT treatment, the net NO3 − flux rate in the root hair zone and vascular bundles of cucumber seedlings decreased, whereas the net NH4 + flux rate in vascular bundles of the midrib, lateral vein, and shoot tip increased. Accordingly, the relative expression of CsNRT1.4a in the petiole and midrib was down-regulated, whereas the expression of CsAMT1.2a–1.2c in the midrib was up-regulated. The results of 15N isotope tracing showed that NO3 −-N and NH4 +-N uptake of the seedlings under LT treatment decreased significantly compared with that under NT treatment, and the concentration and proportion of both NO3 −-N and NH4 +-N distributed in the shoot decreased. Under LT treatment, the actual nitrate reductase activity (NRAact) in the root did not change significantly, whereas NRAact in the stem and petiole increased by 113.2 and 96.2%, respectively. Conclusions The higher net NH4 + flux rate in leaves and young tissues may reflect the higher NRAact in the stem and petiole, which may result in a higher proportion of NO3 − being reduced to NH4 + during the upward transportation of NO3 −. The results contribute to an improved understanding of the mechanism of changes in nitrate transportation in plants in response to low-temperature stress.

Abstract 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.

Abstract Background This study is to describe the design and surgical techniques of three- dimensional-printed porous implants for proximal giant cell tumors of bone and evaluate the short-term clinical outcomes. Methods From December 2016 to April 2020, 8 patients with giant cell tumor of bone in the proximal tibia underwent intralesional curettage of the tumor and reconstruction with bone grafting and three-dimensional-printed porous implant. Detailed anatomy data were measured, including the size of lesion and thickness of the subchondral bone. Prostheses were custom-made for each patient by our team. All patients were evaluated regularly and short-term clinical outcomes were recorded. Results The mean follow-up period was 26 months. According to the different defect sizes, the mean size of the plate and mean length of strut were 35 × 35 mm and 20 mm, respectively. The mean affected subchondral bone percentage was 31.5%. The average preoperative and postoperative thickness of the subchondral bone was 2.1 mm and 11.1 mm, respectively. There was no wound infection, skin necrosis, peroneal nerve injury, or other surgical related complications. No degeneration of the knee joint was found. Osseointegration was observed in all patients. The MSTS improved from an average of 12 preoperatively to 28 postoperatively. Conclusion The application of three-dimensional-printed printed porous prosthesis combined autograft could supply enough mechanical support and enhance bone ingrowth. The design and operation management lead to satisfactory subchondral bone reconstruction.

Abstract Background Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. Method and results This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16). Conclusions Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.

Abstract Background Although septal myectomy is a standard strategy for managing patients with hypertrophic obstructive cardiomyopathy (HOCM) and drug-refractory symptoms, so far, only a few experienced myectomy centers exist globally. Mainly, this can be explained by the many technical challenges presented by myectomy. From our clinical experience, applying the mini-invasive surgical instruments during myectomy potentially reduces the technical difficulty. This study reports the preliminary experience regarding transaortic septal myectomy using mini-invasive surgical instruments for managing patients with HOCM and drug-refractory symptoms; also, we evaluate the early results following myectomy. Methods Between March 2016 and March 2019, consecutive HOCM patients who underwent isolated transaortic septal myectomy using the mini-invasive surgical instruments were enrolled in this analysis. Intraoperative, in-hospital and follow-up results were analyzed. Results We included 168 eligible patients (83 males, mean 56.8 ± 12.3 years). The midventricular obstruction was recorded in 7 (4.2%) patients. All patients underwent transaortic septal myectomy with a mean aortic cross-clamping time of 36.0 ± 8.1 min. During myectomy, 9 (5.4%) patients received repeat aortic cross-clamping. Surgical mortality was 0.6%. Notably, 5 (3.0%) patients developed complete atrioventricular block, they needed permanent pacemaker implantation. The median follow-up time was 6 months; however, no follow-up deaths occurred with a significant improvement in New York Heart Association functional status. We reported a sharp decrease in the maximum gradients from the preoperative value (11.6 ± 7.4 mmHg vs. 94.4 ± 22.6 mmHg, p

Abstract Background Behavioural interventions for the early prevention of childhood obesity mostly focus on English-speaking populations in high-income countries. Cultural adaptation is an emerging strategy for implementing evidence-based interventions among different populations and regions. This paper describes the initial process of culturally adapting Healthy Beginnings, an evidence-based early childhood obesity prevention program, for Arabic and Chinese speaking migrant mothers and infants in Sydney, Australia. Methods The cultural adaptation process followed the Stages of Cultural Adaptation theoretical model and is reported using the Framework for Reporting Adaptations and Modifications-Enhanced. We first established the adaptation rationale, then considered program underpinnings and the core components for effectiveness. To inform adaptations, we reviewed the scientific literature and engaged stakeholders. Consultations included focus groups with 24 Arabic and 22 Chinese speaking migrant mothers and interviews with 20 health professionals. With input from project partners, bi-cultural staff and community organisations, findings informed cultural adaptations to the content and delivery features of the Healthy Beginnings program. Results Program structure and delivery mode were retained to preserve fidelity (i.e. staged nurse calls with key program messages addressing modifiable obesity-related behaviours: infant feeding, active play, sedentary behaviours and sleep). Qualitative analysis of focus group and interview data resulted in descriptive themes concerning cultural practices and beliefs related to infant obesity-related behaviours and perceptions of child weight among Arabic and Chinese speaking mothers. Based on the literature and local study findings, cultural adaptations were made to recruitment approaches, staffing (bi-cultural nurses and project staff) and program content (modified call scripts and culturally adapted written health promotion materials). Conclusions This cultural adaptation of Healthy Beginnings followed an established process model and resulted in a program with enhanced relevance and accessibility among Arabic and Chinese speaking migrant mothers. This work will inform the future cultural adaptation stages: testing, refining, and trialling the culturally adapted Healthy Beginnings program to assess acceptability, feasibility and effectiveness.

Abstract Background Uncemented allograft prosthesis composite (APC) has been applied for tumorous bone defect reconstruction in the proximal femur. However, the long-term results are rarely reported. This study aimed to evaluate long-term outcomes of uncemented APC. Methods Eighteen patients who received uncemented APC reconstruction in the proximal femur after tumor resections were retrospectively reviewed. Results The average resection length was 110 mm (80–154) and the average follow-up was 106.7 months (65–141). Bone union achieved in all patients with an average duration of 7.6 months (5–10). The average HHS, MSTS score and gluteus medius strength at one-year follow-up were 88.0 (80–94), 25.2 (22–28) and 4 (3–5), respectively. While at the last follow-up, the HHS, MSTS score and gluteus medius strength were 83.0 (48–100), 24.0 (10–30) and 4 (2–5), respectively. Five intraoperative fractures were fixed with cerclage wires. Two postoperative periprosthetic and prosthetic fractures received a revision. Three local recurrent patients received a secondary surgery. One of these three lung metastatic patients underwent lung metastatic tumor resection. Another two patients were diagnosed with both bone and lung metastases, only one of them underwent amputation. Two greater trochanteric fractures received no treatment. There were10 severe, 3 moderate and 5 mild allograft resorptions without treatment. Conclusion Uncemented APC is a reliable reconstruction for neoplastic bone defect of the proximal femur, especially for the young patient who expected long-life expectancy and good function. Though allograft resorption and trochanteric fracture are the common complications, they seem no effect on the function.

Abstract Background Increasingly, public health interventions are delivered via telephone and/or text messages. Recent systematic reviews of early childhood obesity prevention interventions have not adequately reported on the way interventions are delivered and the experiences/perceptions of stakeholders. We aimed to summarise the literature in early childhood obesity prevention interventions delivered via telephone or text messages for evidence of application of process evaluation primarily to evaluate stakeholders’ acceptability of interventions. Methods A systematic search of major electronic databases was carried out using the Population, Intervention, Comparison, Outcomes framework. Studies were included if interventions were delivered via telephone/text messages; aimed at changing caregivers’ behaviours to prevent early childhood obesity; with one or more outcomes related to early obesity risk factors such as breastfeeding, solid feeding, tummy time, sleep and settling, physical activity and screen time; published from inception to May 2020. All eligible studies were independently assessed by two reviewers using the Cochrane Collaboration tool for assessing risk of bias. Qualitative studies were assessed using the Consolidated Criteria for Reporting Qualitative Research and Standards for Reporting Qualitative Research tools. Results Twenty-four studies were eligible, and the overall risk of bias was low. Eight studies (33%) had evidence of process evaluation that examined participants’ perceptions of interventions. Participants appreciated the convenience of receiving interventions via telephone or text messages. 63% of all studies in this review showed improvement in one or more behaviours related to childhood obesity prevention. Participants were likely to modify behaviours if they received information from a credible source such as from health professionals. Conclusion There is limited reporting of stakeholders’ experiences in early obesity prevention studies delivered by telephone or text messages. Only one-third of studies examined participants’ acceptability and the potential for delivery of childhood obesity prevention interventions conveniently using this mode of delivery. Interventions delivered remotely via telephone or text messages have the potential to reach equal or a greater number of participants than those delivered via face-to-face methods. Future research should build in process evaluation alongside effectiveness measurements to provide important insight into intervention reach, acceptability and to inform scale up. Trial registration PROSPERO registration: CRD42019108658

Abstract Background The role of a tourniquet is still controversial for patients undergoing total knee arthroplasty (TKA). Our current study was performed to determine whether the nonuse of the tourniquet combine with tranexamic acid (TXA) application in TKA patients with end-stage osteoarthritis would accelerate the perioperative recovery rate and provide enough cement mantle thickness for implant fixation. Methods In this prospective, randomized controlled trial, 150 end-stage knee osteoarthritis patients receiving TKA were divided into three groups: group A (tourniquet group), group B (non-tourniquet group), and group C (tourniquet in cementation group). All enrolled patients received 3 g of intravenous TXA and 1 g topical TXA. The primary outcomes included blood loss variables and transfusion values. The secondary outcomes included VAS pain score, inflammatory factors level, range of motion, HSS score, postoperative hospital stay, and complication. Furthermore, by using a digital linear tomosynthesis technique, tibial baseplate bone cement mantle thickness was measured in four zones based on the knee society scoring system. Results No significant difference was found among the three groups with regards to total blood loss, transfusion, and complication. However, patients in group B showed lower inflammatory factors levels, shorter length of hospital stay, better range of motion, and lower postoperative pain. No significant difference was found among the three groups in four zones in terms of bone cement mantle thickness. Conclusions For end-stage knee osteoarthritis patients, the absence of tourniquet did not appear to affect blood loss and cement penetration in TKA patients. Furthermore, less inflammation reaction and better knee function can be achieved without a tourniquet. We recommend no longer use a tourniquet in primary TKA for patients with end-stage osteoarthritis when TXA is administrated. Trial registration ChiCTR-INR-16009026 . Level of evidence Therapeutic Level I.

Abstract Purpose To evaluate the operation and early clinical effect in primary total knee arthroplasty (TKA) about the novel combination of CT-based patient-specific three-dimensional (3D) preoperative design and conventional osteotomy instruments, compared with the conventional method. Methods After a 1:1 propensity score-matching (PSM), patients were matched to the novel technique group and the conventional group, 109 cases in each group. The conventional group adopted a preoperative design based on a full-length radiograph (FLX) and received TKA with conventional osteotomy instruments. The novel technique group used a CT-based patient-specific 3D preoperative design combined with conventional osteotomy instruments; during the surgery, the femoral entry point, femoral valgus osteotomy angle, the fix point of tibial plateau extramedullary guide pin, and the position of tibial extramedullary positioning rod were accurately selected according to the preoperative 3D design to ensure accurate intraoperative implementation. The lower limb alignment, component position, operation time, tourniquet time, hospital stay, blood loss volume, incidence of postoperative complications, visual analog scale (Vas) score, and New Knee Society Score System (NEW-KSS) at 1 day before operation and 1, 6, and 12 months after operation were recorded and compared. Results The novel technique group was significantly better than the conventional group in controlling lateral tibial component angle (LTC) (P < 0.001), and the novel technique group had lower percentages of hip-knee-ankle angle (HKA) outliers (P < 0.001) and overcorrection (P = 0.003). The operation time, tourniquet time, and hospital stay of the novel technique group was shorter (P < 0.05). In 1 month after the operation, the novel technique group achieved a significantly better VAS score (P < 0.05), but a similar NEW-KSS score (P > 0.05) when compared with the conventional group. But in 6 and 12 months after surgery, no statistical differences were seen in the above two scores (P > 0.05). Conclusion The novel technique of CT-based patient-specific 3D preoperative design combined with conventional instruments can improve the accuracy of osteotomy in primary total knee arthroplasty, with benefits of significantly reducing pain and rapid recovery during the early postoperative period, but having no obvious effect on outcome after a 1-year follow-up.

Abstract Background There are several types of tenodesis reconstruction designed for subtalar instability. However, no comprehensive comparison has been conducted among these procedures in terms of their correcting power so far. The objective of this study is to evaluate the biomechanical behaviors of 5 representative procedures through finite element analysis. Methods Finite element models were established and validated based on one of our previous studies. The Pisani interosseous talocalcaneal ligament (ITCL) reconstruction, Schon cervical ligament (CL) reconstruction and Choisne calcaneofibular ligament (CFL) reconstruction were compared on the model with the CFL, ITCL and CL sectioned. The Schon triligamentous reconstruction and Mann triligamentous reconstruction were compared on the model with the CFL, ITCL and CL, as well as the ATFL sectioned. The inversion and external/internal rotation were quantified at different ankle positions based on the rotational moment. Then, the stress in ligaments and reconstructed grafts and the contact characteristics of the subtalar joint under inversional stress test were calculated and compared accordingly. Results For single ligament reconstruction, the Choisne CFL reconstruction provided the greatest degree of correction for subtalar instability, followed by the Schon CL reconstruction and then the Pisani ITCL reconstruction. For triligamentous reconstruction, the Mann procedure outperformed the Schon procedure in alleviating the subtalar instability. Conclusion The finite element analysis showed that the Choisne CFL reconstruction and Mann triligamentous reconstruction provided the greatest degree of immediate postoperative subtalar stability. However, both procedures could not restore the biomechanical behaviors of the subtalar joint to normal. The long-term efficacy of these procedures warrants further investigation using a substantially larger sample of clinical cases.

Abstract Background Lingzhi and Yunzhi are medicinal mushrooms commonly used with cytotoxic chemotherapy in cancer patients in Asian countries. The current systematic review aims to identify potential pharmacokinetic or pharmacodynamic interactions from the existing literature to ensure their effective and safe combination usage in cancer patients. Methods A systematic search was conducted on nine major Chinese and English databases, including China Journal Net, Allied and Complementary Medicine Database, and Ovid MEDLINE®, etc., to identify clinical, animal, and in-vitro studies that evaluate the effect of combined use of Lingzhi or Yunzhi with cytotoxic drugs. The Jadad scale was used to assess the quality of clinical studies. Results This search identified 213 studies, including 77 clinical studies that reported on the combined use of cytotoxic drugs with Yunzhi (n = 56) or Lingzhi (n = 21). Majority of these clinical studies demonstrated modest methodological quality. In clinical practice, the most commonly used cytotoxic drugs with Lingzhi were cisplatin, 5-fluorouracil (5-FU) and paclitaxel, whereas Tegafur/uracil (UFT)/Tegafur, 5-FU, and mitomycin were the ones used more often with Yunzhi. Only two clinical pharmacokinetic studies were available showing no significant interactions between Polysaccharide K (PSK) and Tegafur. From the pharmacodynamic interactions perspective, combination uses of Yunzhi/Lingzhi with cytotoxic drugs in clinical practice could lead to improvement in survival (n = 31) and quality of life (n = 17), reduction in tumor lesions (n = 22), immune modulation (n = 38), and alleviation of chemotherapy-related side effects (n = 14) with no reported adverse effects. Conclusion Our findings suggest that the clinical combination use of Lingzhi or Yunzhi with cytotoxic drugs could enhance the efficacy and ameliorate the adverse effects of cytotoxic drugs, leading to improved quality of life in cancer patients. More high quality clinical studies including pharmacokinetic herb-drug interactions studies are warranted to verify these observations and mechanisms involved. Based on the high quality clinical data, pharmacoepidemiology methods and bioinformatics or data mining could be adopt for further identification of clinical meaningful herb-drug interactions in cancer therapies.

Abstract Background This study is to describe the detailed design and surgical techniques of three-dimensional (3D)-printed customized prosthesis for pubic bone defect. Patients and methods Five patients under type III resections were included in this study. Based on radiography data, 3D pelvic model was established and virtual surgery was simulated. Detailed anatomy data were measured including the size and arc of normal pubis, the size of residual bone in acetabular side. Different fixation ways were considered according to shape of defect. After features modification and porous structure design, prostheses were fabricated. The osteotomy guides and plastic models were used during surgery. Result Of 5 cases, the prostheses consist of the type with stem (3, 60%) and the type without stem (2, 40%). Mean follow-up period was 13.6 months (range, 8-24 months). For partial pubis removed cases, the mean length and width of narrowest part of normal superior pubis were 13.19 mm (range, 12.51-14.12 mm) and 7.80 mm (range, 7.18-8.26 mm) respectively. Mean arc of normal pubis was 2.71 rad (range, 2.66-2.73 rad). For the entire pubis resection cases, the mean diameter of narrowest parts and length of normal superior pubis were 11.52 mm (range, 11.13-11.91 mm) and 64.78 mm (range, 63.46-66.09 mm), while the diameter of narrowest part and length of normal inferior pubis were 7.37 mm (range, 7.20-7.54 mm) and 86.43 mm (range, 84.28-88.57 mm). Mean length and arc of intramedullary stem was 20 mm (range, 18-21 mm) and 2.7 rad. Mean screw holes number was 6.3 (range, 6-7) while ultimate screws number in surgeries was 4.3 (range, 4-5). Porous structure with 600-μm-pore size and 70% porosity was applied in parts of contact with residual bone. Conclusion 3D-printed customized prostheses could be a feasible option to reconstruct bone defect after type III resection. The design of 3D-printed customized prostheses is a multi-step process which is based on strict anatomic measurement.

Abstract Background Circulating small extracellular vesicles (sEVs) and its associated proteins are of great interest in the early detection of many diseases. However, there is no gold standard for plasma sEVs isolation, especially for proteomic profiling which could be largely affected by contamination such as lipoproteins and plasma proteins. Previous studies suggested combinations of different sEVs isolation methods could improve the yield and purity of the isolated fractions. Nevertheless, there is no systematic evaluation of size-exclusion chromatography (SEC), ultracentrifugation (UC), and their combination in a proteomic perspective. Results Plasma samples were collected from healthy individuals, and sEVs were separated by one-step SEC, one-step UC, and combining SEC with UC, respectively. Here we exhibited that the purity of sEVs was improved by SEC in contrast to traditional UC. Furthermore, by conducting a SEC procedure followed by UC, we separated sEVs with the highest purity. In the proteomic analysis, 992 protein species were identified in the plasma sEVs isolated by our novel separation method, of which several proteins are sEVs-associated proteins but hitherto never been identified in the previous studies and database, much more than plasma sEVs isolated by UC (453) or SEC (682) alone. As compared to Vesiclepedia and Exocarta databases, plasma sEVs isolated by the new procedure kept 584 previously identified sEVs-associated proteins and 360 other proteins that have not been detected before. Detailed analysis suggested that more kinds of sEVs biomarkers, such as CD9, ALIX, and FLOT1, could be identified in plasma sEVs isolated by the novel isolation method as compared to one-step UC/SEC. Furthermore, the lower abundance ranks of common contaminants, such as lipoproteins and IgG chains, in the sEVs fractions obtained by our new method as compared to one-step UC/SEC also demonstrated the purity of sEVs had been improved. Conclusions Combining SEC with UC could significantly improve the performance of mass spectrometry-based proteomic profiling in analyzing plasma-derived sEVs.