Fractures in the distal tibial metaphysis are more complicated to treat than diaphyseal fractures. We compared treatment with plating to treatment with shorted intramedullary (IM) nailing.
Patients ...with AO type 43A fractures were treated with plate fixation (group A,
n
=
14) or shortened IM nailing (group B,
n
=
13). We compared postoperative radiographic deformities, functional results (Iowa ankle scores), and symptoms (Olerud and Molander ankle scores).
All fractures had healed at final follow-up (mean, 33
month). Mean union times were 27.8 week (range, 18–36 week) in group A and 22.6 week (range, 18–30 week) in group B (
P
<
0.05). Mean postoperative valgus angulations were larger in group B (3.7°) than in group A (0.5°) (
P
<
0.05). However, malunions did not differ between groups (
P
<
0.05). Functional results and postoperative symptoms were similar.
Both plate fixation and shortened IM nailing were effective for treating distal tibial metaphyseal fractures.
Faced with increasingly large multicore chip designs, architects need fast and accurate simulations for their exploration of design spaces within a limited simulation time budget. In multithreaded ...applications, threads cannot run simultaneously. Sampling is commonly used to reduce simulation time, but conventional sampling barely detects the instantaneous program variations of synchronization events and the inconsistency between phases of each core. This work proposes a dynamic adjustment and partial sampling technique (DAPs), consisting of aggressive sampling, lazy sampling, and regular sampling, to overcome thread interference in multithreaded applications. Moreover, DAPs partially selects sampling cores to reduce the overhead of sampling inconsistent phases.
The molecular characteristics of prostate cancer (PCa) cells and the immunosuppressive bone tumor microenvironment (TME) contribute to the limitations of immune checkpoint therapy (ICT). Identifying ...subgroups of patients with PCa for ICT remains a challenge. Herein, we report that basic helix-loop-helix family member e22 (BHLHE22) is upregulated in bone metastatic PCa and drives an immunosuppressive bone TME.
In this study, the function of BHLHE22 in PCa bone metastases was clarified. We performed immunohistochemical (IHC) staining of primary and bone metastatic PCa samples, and assessed the ability to promote bone metastasis in vivo and in vitro. Then, the role of BHLHE22 in bone TME was determined by immunofluorescence (IF), flow cytometry, and bioinformatic analyses. RNA sequencing, cytokine array, western blotting, IF, IHC, and flow cytometry were used to identify the key mediators. Subsequently, the role of BHLHE22 in gene regulation was confirmed using luciferase reporter, chromatin immunoprecipitation assay, DNA pulldown, co-immunoprecipitation, and animal experiments. Xenograft bone metastasis mouse models were used to assess whether the strategy of immunosuppressive neutrophils and monocytes neutralization by targeting protein arginine methyltransferase 5 (PRMT5)/colony stimulating factor 2 (CSF2) could improve the efficacy of ICT. Animals were randomly assigned to treatment or control groups. Moreover, we performed IHC and correlation analyses to identify whether BHLHE22 could act as a potential biomarker for ICT combination therapies in bone metastatic PCa.
Tumorous BHLHE22 mediates the high expression of CSF2, resulting in the infiltration of immunosuppressive neutrophils and monocytes and a prolonged immunocompromised T-cell status. Mechanistically, BHLHE22 binds to the
promoter and recruits PRMT5, forming a transcriptional complex. PRMT5 epigenetically activates
expression. In a tumor-bearing mouse model, ICT resistance of Bhlhe22
tumors could be overcome by inhibition of Csf2 and Prmt5.
These results reveal the immunosuppressive mechanism of tumorous BHLHE22 and provide a potential ICT combination therapy for patients with BHLHE22
PCa.
Tibial intercondylar eminence fractures are uncommon. In a review of the literature, most authors agreed that conservative treatment was suggested for non-displaced fractures. Displaced fractures ...were considered an indication for surgery.
Between April 2000 and November 2001, five adult displaced tibial eminence fractures were treated by arthroscopic reduction and non-absorbable suture fixation. Postoperatively, the knee was immobilized in a hinged knee brace locked in full extension with non-weight bearing for 4 weeks. Range of motion and quadriceps-strengthening exercises were started 4 weeks later. Partial weight-bearing was allowed in the following 4 weeks.
The average follow-up was 24.6 months (range 18-36 months). Subjectively, there was no instability or residual pain in the knee. The patients were able to resume their normal activities. Objectively, the average Lysholm Score was 95.6 (range 93-98). The average knee range of motion was 2 degrees to 135 degrees (range 0 degree-140 degrees). All patients had a negative Lachman's test and no pivot shift phenomenon. All fractures showed good union according to radiological evaluation.
Arthroscopy-assisted screw fixation is more stable, and it allows early exercise. However, the fragment must be large enough to be fixed with a screw. Comminuted or small fragments present limitations for screw fixation techniques. We used the non-absorbable intraligmentous suture to pull down the fragment regardless of small size or comminuted status. The technique is simple and provided secure fixation without damage to the ACL insertion. A second operation is not required to remove the hardware.
Bone metastasis is the leading cause of tumor-related death in prostate cancer (PCa) patients. Long noncoding RNAs (lncRNAs) have been well documented to be involved in the progression of multiple ...cancers. Nevertheless, the role of lncRNAs in PCa bone metastasis remains largely unclear.
The expression of prostate cancer-associated transcripts was analyzed in published datasets and further verified in clinical samples and cell lines by RT-qPCR and in situ hybridization assays. Colony formation assay, MTT assay, cell cycle analysis, EdU assay, Transwell migration and invasion assays, wound healing assay, and in vivo experiments were carried out to investigate the function of prostate cancer-associated transcript 6 (PCAT6) in bone metastasis and tumor growth of PCa. Bioinformatic analysis, RNA pull-down, and RIP assays were conducted to identify the proteins binding to PCAT6 and the potential targets of PCAT6. The therapeutic potential of targeting PCAT6 by antisense oligonucleotides (ASO) was further explored in vivo.
PCAT6 was upregulated in PCa tissues with bone metastasis and increased PCAT6 expression predicted poor prognosis in PCa patients. Functional experiments found that PCAT6 knockdown significantly inhibited PCa cell invasion, migration, and proliferation in vitro, as well as bone metastasis and tumor growth in vivo. Mechanistically, METTL3-mediated m
A modification contributed to PCAT6 upregulation in an IGF2BP2-dependent manner. Furthermore, PCAT6 upregulated IGF1R expression by enhancing IGF1R mRNA stability through the PCAT6/IGF2BP2/IGF1R RNA-protein three-dimensional complex. Importantly, PCAT6 inhibition by ASO in vivo showed therapeutic potential against bone metastasis in PCa. Finally, the clinical correlation of METTL3, IGF2BP2, IGF1R, and PCAT6 was further demonstrated in PCa tissues and cells.
Our study uncovers a novel molecular mechanism by which the m
A-induced PCAT6/IGF2BP2/IGF1R axis promotes PCa bone metastasis and tumor growth, suggesting that PCAT6 may serve as a promising prognostic marker and therapeutic target against bone-metastatic PCa.
BACKGROUNDBone metastasis is the leading cause of tumor-related death in prostate cancer (PCa) patients. Long noncoding RNAs (lncRNAs) have been well documented to be involved in the progression of ...multiple cancers. Nevertheless, the role of lncRNAs in PCa bone metastasis remains largely unclear.METHODSThe expression of prostate cancer-associated transcripts was analyzed in published datasets and further verified in clinical samples and cell lines by RT-qPCR and in situ hybridization assays. Colony formation assay, MTT assay, cell cycle analysis, EdU assay, Transwell migration and invasion assays, wound healing assay, and in vivo experiments were carried out to investigate the function of prostate cancer-associated transcript 6 (PCAT6) in bone metastasis and tumor growth of PCa. Bioinformatic analysis, RNA pull-down, and RIP assays were conducted to identify the proteins binding to PCAT6 and the potential targets of PCAT6. The therapeutic potential of targeting PCAT6 by antisense oligonucleotides (ASO) was further explored in vivo.RESULTSPCAT6 was upregulated in PCa tissues with bone metastasis and increased PCAT6 expression predicted poor prognosis in PCa patients. Functional experiments found that PCAT6 knockdown significantly inhibited PCa cell invasion, migration, and proliferation in vitro, as well as bone metastasis and tumor growth in vivo. Mechanistically, METTL3-mediated m6 A modification contributed to PCAT6 upregulation in an IGF2BP2-dependent manner. Furthermore, PCAT6 upregulated IGF1R expression by enhancing IGF1R mRNA stability through the PCAT6/IGF2BP2/IGF1R RNA-protein three-dimensional complex. Importantly, PCAT6 inhibition by ASO in vivo showed therapeutic potential against bone metastasis in PCa. Finally, the clinical correlation of METTL3, IGF2BP2, IGF1R, and PCAT6 was further demonstrated in PCa tissues and cells.CONCLUSIONSOur study uncovers a novel molecular mechanism by which the m6 A-induced PCAT6/IGF2BP2/IGF1R axis promotes PCa bone metastasis and tumor growth, suggesting that PCAT6 may serve as a promising prognostic marker and therapeutic target against bone-metastatic PCa.
Thirty-one knees with symptomatic total knee arthroplasty were diagnosed and treated arthroscopically. There were 18 knees with soft tissue impingement and 13 knees without. There were 16 knees with ...painful arthroplasty and range of motion (ROM) greater than 90°. Hypertrophied synovitis with or without impingement was more easily found by arthroscopy in this group than in the other 15 knees with the chief complaint of limited ROM, where more remarkable fibrotic tissue with intra-articular adhesion was found. Overall, the average improvement in ROM was 43.1° immediately after arthroscopy, and 20° at the final follow-up. Symptoms improved in 90.3% of patients, and 58.1% were satisfied with the outcome of their surgery. Arthroscopy is helpful for intra-articular diagnosis, obtaining a specimen for histopathologic analysis, culture for subclinical infection, and better improvement in ROM. In our experience, arthros-copy for symptomatic knee arthroplasty is reliable, safe and effective.
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