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Journal of Experimental Orthopaedics Jul 2024Popliteal artery laceration is a devastating complication in total knee arthroplasty (TKA). Its anatomic position relative to the tibia has been studied using ultrasound...
PURPOSE
Popliteal artery laceration is a devastating complication in total knee arthroplasty (TKA). Its anatomic position relative to the tibia has been studied using ultrasound or magnetic resonance imaging. This is the first study performed in a laboratory using radiographic measurements to determine if increased flexion and subluxation of the knee increase the distance between the tibia and popliteal artery.
METHODS
The femoral artery was infused with radiopaque dye in six cadavers. The knee was placed in two different degrees of flexion and three of subluxation. The radiographic distance between standardized markers in the posterior tibia and popliteal artery was measured.
RESULTS
The average distance from the tibial peg to the popliteal artery at 90° of flexion increased from 0% to 50% to 100% subluxation. The increase was statistically significant (Friedman test = 0.016). The contrast between neutral and 100% subluxation was statistically significant (Sign test = 0.031). At 115° flexion, average distance from the peg to popliteal artery significantly increased as subluxation increased (Friedman test = 0.05). In three specimens, at 115° of flexion and 100% subluxation, a line perpendicular to the axis of the tibia, failed to intersect the popliteal artery. The measured distance increased from 90° to 115° of flexion at a given degree of subluxation, but this difference did not reach statistical significance.
CONCLUSIONS
Increasing flexion and subluxation of the tibia results in increasing distance between the cut plane of the tibial plateau and popliteal artery and decreases risk of laceration.
LEVEL OF EVIDENCE
Not applicable.
PubMed: 38957228
DOI: 10.1002/jeo2.12070 -
Spine Jul 2024Retrospective study.
STUDY DESIGN
Retrospective study.
OBJECTIVE
We sought to compare surgical outcomes according to baseline balance statuses in elderly patients with degenerative sagittal imbalance (DSI).
SUMMARY OF BACKGROUND
Although optimal sagittal correction has been emphasized for good surgical outcomes, the effect of the state of preoperative balance on surgical outcome has been adequately described at present.
METHODS
Patients aged ≥60 years with DSI who underwent ≥5-level fusion to the sacrum were included. Among them, only those who postoperatively achieved the optimal age-adjusted pelvic incidence (PI) - lumbar lordosis (LL) target were included in this study. Study participants were divided into two groups according to their preoperative sagittal vertical axis (SVA): compensatory balance (SVA <5 cm, group CB) and decompensation (SVA ≥5 cm, group D). Comparisons between the two groups were performed using the chi-squared test or Fisher's exact test for categorical variables and the independent t- test or Wilcoxon rank- sum test for continuous variables.
RESULTS
A total of 156 patients whose postoperative sagittal alignment matched the age-adjusted PI-LL target constituted the study cohort. There were 59 patients in group CB and 97 patients in group D. Mean follow-up duration was 50.0 months after surgery. Immediate postoperatively, sacral slope and SVA were significantly greater in group D than in group CB. At last follow-up, the SVA was significantly greater in group D than in group CB (43.6 vs. 22.7 mm), while no significant differences were found in other sagittal parameters. The Oswestry disability index and Scoliosis Research Society -22 scores at the last follow-up were significantly worse in group D than in group CB.
CONCLUSION
The SVA tended to experience less correction postoperatively, with evidence of further deterioration during follow-up in group D than in group CB. This suboptimal correction of SVA may contribute to the inferior clinical outcomes encountered in group D relative to group CB. Therefore, we recommend correction of PI-LL as close as possible to the lower limit of the suggested PI-LL target range in patients with evidence of preoperative decompensation.
PubMed: 38956981
DOI: 10.1097/BRS.0000000000005090 -
Cell Proliferation Jul 2024The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs)....
The presence of extensive infiltrated macrophages with impaired phagocytosis is widely recognised as a significant regulator for the development of endometriosis (EMs). Nevertheless, the metabolic characteristics and the fundamental mechanism of impaired macrophage phagocytosis are yet to be clarified. Here, we observe that there is the decreased expression of haematopoietic cellular kinase (HCK) in macrophage of peritoneal fluid from EMs patients, which might be attributed to high oestrogen and hypoxia condition. Of note, HCK deficiency resulted in impaired macrophage phagocytosis, and increased number and weight of ectopic lesions in vitro and in vivo. Mechanistically, this process was mediated via regulation of glutamine metabolism, and further upregulation of macrophage autophagy in a c-FOS/c-JUN dependent manner. Additionally, macrophages of EMs patients displayed insufficient HCK, excessive autophagy and phagocytosis dysfunction. In therapeutic studies, supplementation with glutamine-pre-treated macrophage or Bafilomycin A1 (an autophagy inhibitor)-pre-treated macrophage leads to the induction of macrophage phagocytosis and suppression of EMs development. This observation reveals that the aberrant HCK-glutamine-autophagy axis results in phagocytosis obstacle of macrophage and further increase the development risk of Ems. Additionally, it offers potential therapeutic approaches to prevent EMs, especially patients with insufficient HCK and macrophage phagocytosis dysfunction.
PubMed: 38956970
DOI: 10.1111/cpr.13702 -
Advanced Science (Weinheim,... Jul 2024Although hypoxia is known to be associated with immune resistance, the adaptability to hypoxia by different cell populations in the tumor microenvironment and the...
Although hypoxia is known to be associated with immune resistance, the adaptability to hypoxia by different cell populations in the tumor microenvironment and the underlying mechanisms remain elusive. This knowledge gap has hindered the development of therapeutic strategies to overcome tumor immune resistance induced by hypoxia. Here, bulk, single-cell, and spatial transcriptomics are integrated to characterize hypoxia associated with immune escape during carcinogenesis and reveal a hypoxia-based intercellular communication hub consisting of malignant cells, ALCAM macrophages, and exhausted CD8 T cells around the tumor boundary. A hypoxic microenvironment promotes binding of HIF-1α complex is demonstrated to the ALCAM promoter therefore increasing its expression in macrophages, and the ALCAM macrophages co-localize with exhausted CD8 T cells in the tumor spatial microenvironment and promote T cell exhaustion. Preclinically, HIF-1ɑ inhibition reduces ALCAM expression in macrophages and exhausted CD8 T cells and potentiates T cell antitumor function to enhance immunotherapy efficacy. This study reveals the systematic landscape of hypoxia at single-cell resolution and spatial architecture and highlights the effect of hypoxia on immunotherapy resistance through the ALCAM macrophage-exhausted T cell axis, providing a novel immunotherapeutic strategy to overcome hypoxia-induced resistance in cancers.
PubMed: 38956900
DOI: 10.1002/advs.202309885 -
BMC Women's Health Jul 2024Breast cancer has become a major public health problem in the current society, and its incidence rate ranks the first among Chinese female malignant tumors. This paper...
BACKGROUND
Breast cancer has become a major public health problem in the current society, and its incidence rate ranks the first among Chinese female malignant tumors. This paper once again confirmed the efficacy of lncRNA in tumor regulation by introducing the mechanism of the diagnosis of breast cancer by the MIR497HG/miR-16-5p axis.
METHODS
The abnormal expression of MIR497HG in breast cancer was determined by RT-qPCR method, and the correlation between MIR497HG expression and clinicopathological characteristics of breast cancer patients was analyzed via Chi-square test. To understand the diagnostic potential of MIR497HG in breast cancer by drawing the receiver operating characteristic curve (ROC). The overexpressed MIR497HG (pcDNA3.1-MIR497HG) was designed and constructed to explore the regulation of elevated MIR497HG on biological function of BT549 and Hs 578T cells through Transwell assays. Additionally, the luciferase gene reporter assay and Pearson analysis evaluated the targeting relationship of MIR497HG to miR-16-5p.
RESULTS
MIR497HG was decreased in breast cancer and had high diagnostic function, while elevated MIR497HG inhibited the migration and invasion of BT549 and Hs 578T cells. In terms of functional mechanism, miR-16-5p was the target of MIR497HG, and MIR497HG reversely regulated the miR-16-5p. miR-16-5p mimic reversed the effects of upregulated MIR497HG on cell biological function.
CONCLUSIONS
In general, MIR497HG was decreased in breast cancer, and the MIR497HG/miR-16-5p axis regulated breast cancer tumorigenesis, providing effective insights for the diagnosis of patients.
Topics: Humans; MicroRNAs; Female; Breast Neoplasms; RNA, Long Noncoding; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Cell Movement; Middle Aged; Cell Proliferation
PubMed: 38956558
DOI: 10.1186/s12905-024-03208-7 -
Cellular & Molecular Biology Letters Jul 2024Anti-angiogenic therapy has become one of the effective treatment methods for tumors. Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis...
BACKGROUND
Anti-angiogenic therapy has become one of the effective treatment methods for tumors. Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and angiogenesis in EC. However, the underlying mechanisms of lncRNA TRPM2-AS in EC are still not clear.
METHODS
We screened the differently expressed lncRNAs that were highly associated with poor prognosis and angiogenesis of EC by bioinformatics analysis, and constructed a ceRNA network based on the prognostic lncRNAs. The subcellular localization of TRPM2-AS was determined by fluorescence in situ hybridization (FISH) and nuclear cytoplasmic fractionation assay. CCK-8, EdU, transwell, western blot, qRT-PCR and endothelial tube formation assay were used to evaluate the effects of TRPM2-AS on the proliferation, invasion, migration of EC cells and angiogenesis. The targeted microRNA (miRNA) of TRPM2-AS was predicted by bioinformatic methods. The interaction between TRPM2-AS and miR497-5p, miR497-5p and SPP1 were analyzed by RNA immunoprecipitation and dual-luciferase reporter assay. A subcutaneous tumor model was used to explore TRPM2-AS's function in vivo. CIBERSORT was used to analyze the correlation between TRPM2-AS and immune cell immersion in EC.
RESULTS
We found that the expression of TRPM2-AS and SPP1 was aberrantly upregulated, while miR-497-5p expression was significantly downregulated in EC tissues and cells. TRPM2-AS was closely correlated with the angiogenesis and poor prognosis in EC patients. Mechanistically, TRPM2-AS could sponge miR-497-5p to release SPP1, thus promoting the proliferation, invasion and migration of EC cells and angiogenesis of HUVECs. Knockdown of TRPM2-AS in xenograft mouse model inhibited tumor proliferation and angiogenesis in vivo. In addition, TRPM2-AS plays a vital role in regulating the tumor immune microenvironment of EC, overexpression of TRPM2-AS in EC cells stimulated the polarization of M2 macrophages and angiogenesis through secreting SPP1 enriched exosomes.
CONCLUSION
The depletion of TRPM2-AS inhibits the oncogenicity of EC by targeting the miR-497-5p/SPP1 axis. This study offers a better understanding of TRPM2-AS's role in regulating angiogenesis and provides a novel target for EC treatment.
Topics: Humans; MicroRNAs; RNA, Long Noncoding; Neovascularization, Pathologic; Female; Gene Expression Regulation, Neoplastic; Animals; Cell Proliferation; Cell Line, Tumor; Endometrial Neoplasms; Cell Movement; Mice; Disease Progression; Mice, Nude; TRPM Cation Channels; Mice, Inbred BALB C; Prognosis; Angiogenesis
PubMed: 38956502
DOI: 10.1186/s11658-024-00612-7 -
Cellular & Molecular Biology Letters Jul 2024An increasing number of studies have demonstrated the association of circular RNAs (circRNAs) with the pathological processes of various diseases and their involvement...
BACKGROUND
An increasing number of studies have demonstrated the association of circular RNAs (circRNAs) with the pathological processes of various diseases and their involvement in the onset and progression of multiple cancers. Nevertheless, the functional roles and underlying mechanisms of circRNAs in the autophagy regulation of gastric cancer (GC) have not been fully elucidated.
METHODS
We used transmission electron microscopy and the mRFP-GFP-LC3 dual fluorescent autophagy indicator to investigate autophagy regulation. The cell counting kit-8 assay, colony formation assay, 5-ethynyl-2'-deoxyuridine incorporation assay, Transwell assay, and Western blot assay were conducted to confirm circPTPN22's influence on GC progression. Dual luciferase reporter assays validated the binding between circPTPN22 and miR-6788-5p, as well as miR-6788-5p and p21-activated kinase-1 (PAK1). Functional rescue experiments assessed whether circPTPN22 modulates PAK1 expression by competitively binding miR-6788-5p, affecting autophagy and other biological processes in GC cells. We investigated the impact of circPTPN22 on in vivo GC tumors using a nude mouse xenograft model. Bioinformatics tools predicted upstream regulatory transcription factors and binding proteins of circPTPN22, while chromatin immunoprecipitation and ribonucleoprotein immunoprecipitation assays confirmed the binding status.
RESULTS
Upregulation of circPTPN22 in GC has been shown to inhibit autophagy and promote cell proliferation, migration, and invasion. Mechanistically, circPTPN22 directly binds to miR-6788-5p, subsequently regulating the expression of PAK1, which activates protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) phosphorylation. This modulation ultimately affects autophagy levels in GC cells. Additionally, runt-related transcription factor 1 (RUNX1) negatively regulates circPTPN22 expression, while RNA-binding proteins such as FUS (fused in sarcoma) and ELAVL1 (recombinant ELAV-like protein 1) positively regulate its expression. Inhibition of the autophagy pathway can increase FUS expression, further upregulating circPTPN22 in GC cells, thereby exacerbating the progression of GC.
CONCLUSION
Under the regulation of the transcription factor RUNX1 and RNA-binding proteins FUS and ELAVL1, circPTPN22 activates the phosphorylation of Akt and Erk through the miR-6788-5p/PAK1 axis, thereby modulating autophagy in GC cells. Inhibition of autophagy increases FUS, which in turn upregulates circPTPN22, forming a positive feedback loop that ultimately accelerates the progression of GC.
Topics: Humans; Stomach Neoplasms; RNA, Circular; Autophagy; MicroRNAs; p21-Activated Kinases; Cell Proliferation; RNA-Binding Protein FUS; Cell Movement; Cell Line, Tumor; Animals; ELAV-Like Protein 1; Core Binding Factor Alpha 2 Subunit; Gene Expression Regulation, Neoplastic; Mice, Nude; Mice; Neoplasm Invasiveness; Mice, Inbred BALB C
PubMed: 38956466
DOI: 10.1186/s11658-024-00610-9 -
Nature Reviews. Nephrology Jul 2024
PubMed: 38956437
DOI: 10.1038/s41581-024-00867-5 -
Nature Genetics Jul 2024
PubMed: 38956209
DOI: 10.1038/s41588-024-01797-5 -
Angiogenesis Jul 2024The proliferation of the endothelium is a highly coordinated process to ensure the emergence, expansion, and homeostasis of the vasculature. While Bone Morphogenetic...
The proliferation of the endothelium is a highly coordinated process to ensure the emergence, expansion, and homeostasis of the vasculature. While Bone Morphogenetic Protein (BMP) signaling fine-tunes the behaviors of endothelium in health and disease, how BMP signaling influences the proliferation of endothelium and therefore, modulates angiogenesis remains largely unknown. Here, we evaluated the role of Activin A Type I Receptor (ACVR1/ALK2), a key BMP receptor in the endothelium, in modulating the proliferation of endothelial cells. We show that ACVR1/ALK2 is a key modulator for the proliferation of endothelium in the retinal vessels. Loss of endothelial ALK2 leads to a significant reduction in endothelial proliferation and results in fewer branches/endothelial cells in the retinal vessels. Interestingly, venous endothelium appears to be more susceptible to ALK2 deletion. Mechanistically, ACVR1/ALK2 inhibits the expression of CDKN1A/p21, a critical negative regulator of cell cycle progression, in a SMAD1/5-dependent manner, thereby enabling the venous endothelium to undergo active proliferation by suppressing CDKN1A/p21. Taken together, our findings show that BMP signaling mediated by ACVR1/ALK2 provides a critical yet previously underappreciated input to modulate the proliferation of venous endothelium, thereby fine-tuning the context of angiogenesis in health and disease.
PubMed: 38955953
DOI: 10.1007/s10456-024-09936-6