High expression of ACKR1 predicts a good prognosis and suppresses sarcoma cell progression via regulating the tumor immune microenvironment.

Sarcoma is a malignant tumor originating from mesenchymal tissue with a poor prognosis. Atypical chemokine receptor 1 (ACKR1) is found closely related to cancer progression. However, the effects of ACKR1 in soft tissue sarcoma have not been well investigated. Therefore, our present study is devoted to analyze the functions of ACKR1 in sarcoma progression and its potential mechanism. We detected the expression of ACKR1 in the Cancer Genome Atlas (TCGA)-pan-cancer database, TCGA-Sarcoma from TCGA databases, and GSE21122 from Gene Expression Omnibus (GEO) database. The relationships between ACKR1 expression, clinicopathological data, and survival status were evaluated in the TCGA-Sarcoma database. Moreover, overexpression negative control (OE-NC) and overexpression ACKR1 (OE-ACKR1) were used to further verify the effects of ACKR1 overexpression in the progression of sarcoma cells by using Reverse Transcription-Quantitative Polymerase Chain Reaction (RT-qPCR), cell counting kit-8 (CCK-8), 5-Ethyny-2'-Deoxyuridine (EdU), wound healing, transwell assay, and flow cytometry assays. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) analyses were carried out to explore the potential enriched biological process of ACKR1 expression in sarcoma. Furthermore, tumor-immune system interactions databases (TISIDB) were applied to further confirm the relations between ACKR1 and tumor immune microenvironment in sarcoma. Our study found that ACKR1 is downregulated in multiple cancers (including sarcoma), and low expression of ACKR1 is related to poor survival status in sarcoma. The biological experiments found that promoting expression of ACKR1 can suppress sarcoma cell proliferation, migration, invasion, promote cell apoptosis, and arrest cell cycle. The GO-KEGG, GSEA, and TISIDB analysis showed that ACKR1 is related to the tumor immune microenvironment. In conclusion, low expression of ACKR1 presented as an independent prognostic biomarker in sarcoma. Overexpression of ACKR1 can significantly suppress cell progression ability in sarcoma by regulating the immune microenvironment.

[Effectiveness of vacuum sealing drainage combined with modified external fixation antibiotic-impregnated cement semi-open technique in treating chronic ulcer wounds].

Objective: To investigate the effectiveness of debridement-vacuum sealing drainage (VSD)-modified external fixation antibiotic-impregnated cement semi-open technique in treatment of chronic ulcer wounds. Methods: Clinical data of 43 patients with chronic ulcer wounds who met the selection criteria and admitted between January 2019 and June 2023 were retrospectively analyzed. Among them, 23 cases were treated with debridement-VSD-modified external fixation antibiotic-impregnated cement semi-open technique (improved group), and 20 cases were treated with debridement-VSD-traditional antibiotic-impregnated cement technique (control group). There was no significant difference in gender, age, constituent ratio of patients with type 2 diabetes mellitus, constituent ratio of patients with smoking history, body mass index, wound site, and other baseline data between the two groups ( P>0.05). The healing quality and healing time, the positive rate of bacterial culture after bone cement coating, the loosening rate of bone cement, the number of operations, the number of hospitalizations, the length of hospitalization, and the cost of hospitalization were recorded and compared between the two groups. Results: Compared with the control group, the positive rate of bacterial culture after bone cement coating and the loosening rate of bone cement in the improved group was significantly lower, as well as the number of operations, the number of hospitalizations, the length of hospitalization, and hospitalization cost significantly reduced ( P<0.05). Wound repair was completed in both groups without amputation. The wound healing quality of the improved group was better than that of the control group and the wound healing time was shorter, the differences were significant ( P<0.05). All patients were followed up 1-5 years (mean 3.4 years), and no ulcers recurred during follow-up. Conclusion: Debridement-VSD-modified external fixation antibiotic-impregnated cement semi-open technique in the treatment of chronic ulcer wounds can effectively reduce the loosening rate of bone cement, facilitate the induced membrane formation and wound healing, and significantly reduce the number of operations and shorten the length of hospital stay.

[Evaluation of lower limb function and gait characteristics after fibulectomy in adults].

Objective: To explore the effects of fibulectomy on lower limb function and gait of adult patients through gait analysis, in order to provide guidance for clinical treatment. Methods: A clinical data of 24 patients who underwent fibulectomy and met the selection criteria between January 2017 and December 2022 was retrospectively analyzed. There were 12 males and 12 females with an average age of 25 years (range, 18-68 years). The length of fibulectomy was 10-19 cm, with an average of 15 cm. The patients underwent routine rehabilitation training after operation. The occurrence of postoperative complications was recorded, the pain degree of surgical incision was evaluated by visual analogue scale (VAS) score, and the residual fibular bone was reviewed by imaging. A gait test system was used before operation and at 6 months after operation to collect gait data of healthy and affected sides under slow, medium, and fast velocity conditions, including gait parameters (foot rotation angle, step length, support phase, swing phase, gait line length, single support line, maximum force 1, maximum force 2) and the tripod area parameters (maximum pressure, time maximum force, and contact time of forefoot, midfoot, and hindfoot). Results: All incisions healed by first intention after operation. All patients were followed up 1-5 years, with an average of 3 years. The great dorso-extension muscle strength decreased in 3 cases, and the sensory defects in the operative area and distal part occurred in 5 cases. The VAS scores of incisions were 0-6 (mean, 4) at 6 months after operation and 0-5 (mean, 2) at last follow-up. During follow-up, imaging review showed that 5 cases had osteoporotic changes of distal residual bone of the fibula, and the residual segment was shorter and more significant; 3 cases had new bone formation. The results of gait test showed that the gait parameters and the tripod area parameters under the three gait speeds were consistent. There was no significant difference in the gait parameters and the tripod area parameters between the healthy side and the affected side before operation ( P>0.05). Compared with the healthy side, the foot rotation angle, the single support line, the maximum force 1, the maximum force 2, and the maximum pressures of the forefoot and midfoot of the affected side significantly decreased after operation ( P<0.05), and the step length, the time maximum force of midfoot and hindfoot, and the contact time of the forefoot and midfoot significantly increased ( P<0.05). Compared with preoperative conditions on the same side, the foot rotation angle, the gait line length of both sides significantly decreased ( P<0.05), and the maximum pressures of the forefoot, midfoot, and hindfoot and the time maximum force of the midfoot significantly increased ( P<0.05); the step length on healthy side significantly decreased, while the affected side significantly increased ( P<0.05); the maximum force 1 and the maximum force 2 on the healthy side significantly increased, while the affected side significantly decreased ( P<0.05); the single support line on the affected side significantly decreased ( P<0.05). Conclusion: Different degrees of clinical symptoms occurred, gait pattern changes, compensatory gait appears, gait stability decreases, and the risk of tumble increases in adult patients after partial fibulectomy. Therefore, it is recommended to walk slowly after fibulectomy.

Revision of failed metal-on-metal total hip arthroplasty using cemented arthroplasty: a mean 10-year follow-up of 157 consecutive patients.

OBJECTIVE: This study was performed to assess the outcomes of Asian patients who underwent conversion from metal-on-metal total hip arthroplasty (MoM-THA) to cemented THA (CTHA). METHODS: One hundred and fifty-seven consecutive patients (157 hips) who underwent CTHA following primary MoM-THA from January 2005 to February 2015 were retrospectively analysed. The primary endpoints were the clinical outcomes. Follow-ups occurred at 3 months, 6 months, 1 year, 2 years, and then every 2 years following revision of MoM-THA. RESULTS: The mean follow-up after conversion was 10 years (range, 5-14 years). Statistically significant improvements in the mean Harris hip score were observed between the preoperative and final follow-up evaluations (62.71 ± 13.85 vs. 84.03 ± 16.21, respectively). The major orthopaedic complication rate was 16.5% (26/157). Six (3.8%) patients underwent revision at a mean of 3.5 ± 1.3 years after conversion, predominantly because of prosthesis loosening or recurrent dislocation. Nine (5.7%) patients developed prosthesis loosening at a mean of 2.6 ± 1.1 years following conversion, two of whom requested revision surgery. Eleven (7.0%) patients developed prosthesis dislocation, four of whom requested revision surgery. CONCLUSION: CTHA may yield favourable functional outcomes and a reduced rate of major orthopaedic complications.

Hypoxia increases the expression of stem cell markers in human osteosarcoma cells.

Osteosarcoma (OS) is the most common primary malignant tumor of bone. It is a common phenomenon that osteosarcoma cells have a hypoxic microenvironment. Hypoxia can dedifferentiate cells of several malignant tumor types into stem cell-like phenotypes. However, the role of hypoxia in stemness induction and the expression of cancer stem cell (CSC) markers in human osteosarcoma cells has not been reported. The present study examined the effects of hypoxia on stem-like cells in the human osteosarcoma MNNG/HOS cells. Under the incubation with 1% oxygen, the expression of CSCs markers (Oct-4, Nanog and CD133) in MNNG/HOS cells were increased. Moreover, MNNG/HOS cells cultured under hypoxic conditions were more likely to proliferate into spheres and resulted in larger xenograft tumor. Hypoxia also increased the mRNA and protein levels of hypoxia-inducible factor (HIF)-1α. Then rapamycin was used, which has been shown to lower HIF-1α protein level, to inhibit the hypoxic response. Rapamycin suppressed the expression of HIF-1α protein and CSCs markers (Oct4, Nanog and CD133) in MNNG/HOS cells. In addition, pretreatment with rapamycin reduced the efficiency of MNNG/HOS cells in forming spheres and xenograft tumors. The results demonstrated that hypoxia (1% oxygen) can dedifferentiate some of the MNNG/HOS cells into stem cell-like phenotypes, and that the mTOR signaling pathway participates in this process via regulating the expression of HIF-1α protein.

Classification of Osteosarcoma Based on Immunogenomic Profiling.

Accumulating evidence has supported that osteosarcoma is heterogeneous, and several subtypes have been identified based on genomic profiling. Immunotherapy is revolutionizing cancer treatment and is a promising therapeutic strategy. In contrast, few studies have identified osteosarcoma classification based on immune biosignatures, which offer the optimal stratification of individuals befitting immunotherapy. Here, we classified osteosarcoma into two clusters: immunity high and immunity low using the single-sample gene-set enrichment analysis and unsupervised hierarchical clustering. Immunity_H subtype was associated with high immune cells infiltration, a favorable prognosis, benefit to immunotherapy, high human leukocyte antigen gene expression, and activated immune signal pathway indicating an immune-hot phenotype. On the contrary, the Immunity_L subtype was correlated with low immune cell infiltration, poor prognosis, and cancer-related pathway, indicating an immune-cold phenotype. We also identified TYROBP as a key immunoregulatory gene associated with CD8+ T cell infiltration by multiplex immunohistochemistry. Finally, we established an immune-related prognostic model that predicted the survival time of osteosarcoma. In conclusion, we established a new classification system of osteosarcoma based on immune signatures and identified TYROBP as a key immunoregulatory gene. This stratification had significant clinical outcomes for estimating prognosis, as well as the immunotherapy of osteosarcoma patients.

Cemented versus uncemented total hip replacement for femoral neck fractures in elderly patients: a retrospective, multicentre study with a mean 5-year follow-up.

BACKGROUND: Cemented or uncemented total hip replacement (CTR or UTR) for femoral neck fractures (AO/OTA type 31B/C) is a relatively common procedure in elderly individuals. The recent literature is limited regarding long-term outcomes following CTR versus UTR in the Asian population. METHODS: Using our institutional database, we performed long-term outcome analysis on 268 patients with femoral neck fractures (AO/OTA type 31B/C) who had undergone a primary UTR or CTR (CTR: n = 132, mean age, 67.43 ± 6.51 years; UTR: n = 136, mean age, 67.65 ± 6.13 years) during 2007-2014, and these patients were followed until 2019. Follow-up occurred 1, 3, 6, and 12 months postoperatively and yearly thereafter. The primary endpoint was the Harris hip score (HHS); the secondary endpoint was the incidence of orthopaedic complications. RESULTS: The mean follow-up time was 62.5 months (range, 50.1-76.1 months). At the final follow-up, the HHS was 79.39 ± 16.92 vs 74.18 ± 17.55 (CTR vs UTR, respectively, p = 0.011). Between-group significant differences were observed regarding the incidence of prosthesis revision, prosthesis loosening, and periprosthetic fracture (7.6% [95% CI, 6.4-8.2] for CTR vs 16.9% [95% CI, 14.7-17.3] for UTR, p = 0.020; 9.8% [95% CI, 8.3-10.7] for CTR vs 19.9% [95% CI, 18.2-20.9] for UTR, p = 0.022; 5.3% [95% CI, 4.4-6.7] for CTR vs 13.2% [95% CI, 12.1-13.8] for UTR, p = 0.026, respectively). CONCLUSION: CTR showed superiority to UTR by improving the HHS and decreasing the incidence of orthopaedic complications. Our findings need to be confirmed in a prospective, randomized controlled study to verify whether they can be applicable to a broader population.

Mid-term outcomes of uncemented or cemented arthroplasty revision following metal-on-metal total hip arthroplasty failure: a retrospective observational study.

OBJECTIVE: To retrospectively compare the mid-term outcomes of uncemented or cemented total hip arthroplasty (THA) revision for prior primary metal-on-metal (MoM) THA failure. METHODS: Data from 278 patients (278 hips) who underwent uncemented THA (UTHA) or cemented THA (CTHA) for prior primary MoM-THA failure from 2006 to 2016 were retrospectively analysed. Follow-up was performed 6 months, 1 year, 2 years, and then every 2 years after conversion. The mean follow-up time was 96 months (range, 64-128 months). The primary endpoint was the modified Harris hip score (HHS). The secondary endpoint was the major orthopaedic complication rate. RESULTS: The HHS showed significantly greater differences in the CTHA than UTHA group 12 months after conversion. From the 12th month after conversion to the final follow-up, CTHA yielded better functional outcomes than UTHA. There were significant differences between the UTHA and CTHA groups in the rates of re-revision (14.4% vs. 4.9%, respectively), aseptic loosening (17.3% vs. 6.8%, respectively), and periprosthetic fracture (11.5% vs. 3.9%, respectively). CONCLUSION: CTHA has more advantages than UTHA in terms of improving functional outcomes and decreasing the major orthopaedic complication rate.

Long-term follow-up outcomes for patients undergoing primary total hip arthroplasty with uncemented versus cemented femoral components: a retrospective observational study with a 5-year minimum follow-up.

BACKGROUND: This retrospective analysis compared the long-term outcomes for patients with a femoral neck fracture (AO/OTA type 31B) treated with a primary unilateral total hip arthroplasty with uncemented or cemented femoral components (UTHA or CTHA, respectively). METHODS: We conducted a retrospective cohort study using the South China Hip Arthroplasty Database. We identified 422 patients with femoral neck fracture (AO/OTA type 31B) who were previously treated with primary unilateral UTHA or CTHA between 2007 and 2015, with follow-up until 2019. Follow-up occurred 1, 3, 6 and 12 months postoperatively and yearly thereafter. The primary outcome was the Harris hip score (HHS). The secondary outcome was the orthopaedic complication rate. RESULTS: In total, 324 patients (UTHA n = 160, mean age 68.61 ± 7.49 years; CTHA n = 164, mean age 68.75 ± 7.04 years) were evaluated for study eligibility. The median follow-up was 73.3 months (range, 11.6-89.2 months). At the final follow-up, HHS was 74.09 ± 6.23 vs 79.01 ± 10.21 (UTHA vs CTHA, p = 0.012). Significant differences were detected in the incidence of prosthetic revision, loosening, and periprosthetic fracture between the UTHA and CTHA groups (7.5% for UTHA vs 1.8% for CTHA, p = 0.015; 17.5% for UTHA vs 8.5% for CTHA, p = 0.016; 11.9% for UTHA vs 4.9% for CTHA, p = 0.021, respectively). CONCLUSION: In this setting, CTHA demonstrated superiority to UTHA by improving functional outcomes and decreasing complication rates.

Poor outcomes for osteoporotic patients undergoing conversion total hip arthroplasty following prior failed dynamic hip screw fixation: a nationwide retrospective cohort study.

OBJECTIVES: This study was performed to compare the long-term clinical and radiological outcomes of conversion total hip arthroplasty (CTHA) following prior failed InterTan nail (IT) fixation or dynamic hip screw (DHS) fixation in Asian patients with osteoporotic intertrochanteric hip fractures (IHFs) and to clarify which implant tends to be more favourable for CTHA. METHODS: Records of consecutive Asian patients with osteoporosis who underwent conversion of failed primary unilateral IT or DHS fixation to THA from 2010 to 2013 were extracted from the comprehensive database of the China Pacific Insurance Company Ltd. All consecutive procedures were managed by high-volume surgeons. The primary endpoint was the clinical outcome. The secondary endpoint was the radiological outcome. RESULTS: In total, 447 Asian patients with osteoporotic IHFs (DHS, n = 223; IT, n = 224) were assessed during a median follow-up of 46 months (range, 39-53 months). The two groups showed a significant difference in the Harris hip score at final follow-up and in the orthopaedic complication rate (DHS, 20.2%; IT, 9.8%). CONCLUSION: Conversion to THA following prior failed DHS fixation tends to be associated with poorer clinical and radiological outcomes in Asian patients with osteoporotic IHFs than that following prior failed IT fixation.

Verification of TREX1 as a promising indicator of judging the prognosis of osteosarcoma.

BACKGROUND: The study aimed to explore the correlation between the expression of TREX1 and the metastasis and the survival time of patients with osteosarcoma as well as biological characteristics of osteosarcoma cells for the prognosis judgment of osteosarcoma. METHOD: The correlation between the expression of TREX1 protein and the occurrence of pulmonary metastasis in 45 cases of osteosarcoma was analyzed. The CD133+ and CD133- cell subsets of osteosarcoma stem cells were sorted by the flow cytometry. The tumorsphere culture, clone formation, growth curve, osteogenic and adipogenic differentiation, tumor-formation ability in nude mice, sensitivity of chemotherapeutic drugs, and other cytobiology behaviors were compared between the cell subsets in two groups; the expressions of stem cell-related genes Nanog and Oct4 were compared; The expressions of TREX1 protein and mRNA were compared between the cell subsets in two groups. The data was statistically analyzed. The measurement data between the two groups were compared using t test. The count data between the two groups were compared using χ 2 test and Kaplan-Meier survival analysis. A P value <0.05 indicated that the difference was statistically significant. RESULTS: The expression of TREX1 protein in patients with osteosarcoma in the metastasis group was significantly lower than that in the non-metastasis group. The difference was statistically significant (P < 0.05). Up to the last follow-up visit, the former average survival time was significantly lower than that of the latter, and the difference was statistically significant (P < 0.05). The expression of TREX1 in human osteosarcoma CD133+ cell subsets was significantly lower than that in CD133- cell subsets. Stemness-related genes Nanog and Oct4 were highly expressed in human osteosarcoma CD133+ cell subsets with lower expression of TREX1; the biological characteristics identification experiment showed that human CD133+ cell subsets with low TREX1 expression could form tumorspheres, the number of colony forming was more, the cell proliferation ability was strong, the osteogenic and adipogenic differentiation potential was big, the tumor-forming ability in nude mice was strong, and the sensibility of chemotherapeutics drugs on cisplatin was low. CONCLUSIONS: The expression of TREX1 may be related to metastasis in patients with osteosarcoma. The expression of TREX1 was closely related to the cytobiology characteristics of osteosarcoma stem cell. TREX1 can play an important role in the occurrence and development processes. And, TREX1 is expected to become an effective new index for the evaluation of the prognosis.

Overexpressing neuroglobin improves functional recovery by inhibiting neuronal apoptosis after spinal cord injury.

The current study was performed to evaluate the mechanisms and therapeutic effects of overexpressing neuroglobin (Ngb) on spinal cord injury (SCI). Adeno-associated virus (AAV) was injected in the T12 section 7 days before SCI. Animals were randomly divided into four groups: a sham group, a vehicle group, an AAV-EGFP group and an AAV-Ngb group. Recovery of hind limb locomotor function was determined during the 3-week post operation period by the Basso, Beattie and Bresnahan locomotor rating scale. At 24 h after SCI and at the end of the study, the segments of spinal cord, centered with the lesion site were harvested for histopathological analysis. Immunofluorescence was performed using antibodies to recognize neuN in the lesion sections. At 24 h after SCI, the spinal cord tissue samples were removed to analyze tissue concentrations of superoxide dismutase (SOD) and malondialdehyde (MDA). Apoptotic cells were assessed using a terminal deoxynucleotidyl transferase, dUTP nick end labeling (TUNEL) kit. The expression of bcl-2, bax, cytochrome c, and cleaved caspase-3, were determined by Western blot assay and immunostaining analysis. The results showed that animals overexpressing Ngb had significantly greater recovery of locomotor function, less neuronal loss and fewer apoptotic cells. In addition, overexpressing Ngb significantly increased bcl-2 expression and SOD level, decreased bax expression, attenuated the release of cytochrome c from mitochondria to the cytosol fraction, and reduced the activity of caspase-3 and MDA level after SCI. These findings suggest, that overexpressing Ngb can significantly improve the recovery of locomotor function. This neuroprotective effect may be associated with the inhibition of neural apoptosis via the mitochondrial pathway.