Construction of a cuproptosis-related lncRNA signature for predicting prognosis and immune landscape in osteosarcoma patients.

BACKGROUND: Long noncoding RNAs (lncRNAs) influence the onset of osteosarcoma. Cuproptosis is a novel cell death mechanism. We attempted to identify a cuproptosis-related lncRNA signature to predict the prognosis and immune landscape in osteosarcoma patients. METHODS: Transcriptional and clinical data of 85 osteosarcoma patients were derived from the TARGET database and randomly categorized into the training and validation cohorts. We implemented the univariate and multivariate Cox regression, along with LASSO regression analyses for developing a cuproptosis-related lncRNA risk model. Kaplan-Meier curves, C-index, ROC curves, univariate and multivariate Cox regression, and nomogram were used to assess the capacity of this risk model to predict the osteosarcoma prognosis. Gene ontology, KEGG, and Gene Set Enrichment (GSEA) analyses were conducted for determining the potential functional differences existing between the high-risk and low-risk patients. We further conducted the ESTIMATE, single-smaple GSEA, and CIBERSORT analyses for identifying the different immune microenvironments and immune cells infiltrating both the risk groups. RESULTS: We screened out four cuproptosis-related lncRNAs (AL033384.2, AL031775.1, AC110995.1, and LINC00565) to construct the risk model in the training cohort. This risk model displayed a good performance to predict the overall survival of osteosarcoma patients, which was confirmed by using the validation and the entire cohort. Further analyses showed that the low-risk patients have more immune activation and immune cells infiltrating as well as a good response to immunotherapy. CONCLUSIONS: We developed a novel cuproptosis-related lncRNA signature with high reliability and accuracy for predicting outcome and immunotherapy response in osteosarcoma patients, which provides new insights into the personalized treatment of osteosarcoma.

Identification and Development of an Age-Related Classification and Signature to Predict Prognosis and Immune Landscape in Osteosarcoma.

Background: In childhood and adolescence, the prevailing bone tumor is osteosarcoma associated with frequent recurrence and lung metastasis. This research focused on predicting the survival and immune landscape of osteosarcoma by developing a prognostic signature and establishing aging-related genes (ARGs) subtypes. Methods: The training group comprised of the transcriptomic and associated clinical data of 84 patients with osteosarcoma accessed at the TARGET database and the validation group consisted of 53 patients from GSE21257. The aging-related subtypes were identified using unsupervised consensus clustering analysis. The ARG signature was developed utilizing multivariate Cox analysis and LASSO regression. The prognostic value was assessed using the univariate and multivariate Cox analyses, Kaplan-Meier plotter, time-dependent ROC curve, and nomogram. The functional enrichment analyses were performed by GSEA, GO, and KEGG analysis, while the ssGSEA, ESTIMATE, and CIBERSORT analyses were conducted to reveal the immune landscape in osteosarcoma. Results: The two clusters of osteosarcoma patients formed based on 543 ARGs, depicted a considerable difference in the tumor microenvironment, and the overall survival and immune cell infiltration rate varied as well. Among these, the selected 23 ARGs were utilized for the construction of an efficient predictive prognostic signature for the overall survival prediction. The testing in the validation group of osteosarcoma patients confirmed the status of the high-risk score as an independent indicator for poor prognosis, which was already identified as such using the univariate and multivariate Cox analyses. Furthermore, the ARG signature could distinguish different immune-related functions, infiltration status of immune cells, and tumor microenvironment, as well as predict the immunotherapy response of osteosarcoma patients. Conclusion: The aging-related subtypes were identified and a prognostic signature was developed in this research, which determined different prognoses and allowed for treatment of osteosarcoma patients to be tailored. Additionally, the immunotherapeutic response of individuals with osteosarcoma could also be predicted by the ARG signature.

Clinical Characteristics and Treatment of Adult Idiopathic Carpal Tunnel Syndrome Accompanied with Trigger Digit.

Purpose: To investigate the clinical characteristics and treatment of adult idiopathic carpal tunnel syndrome (CTS) accompanied with trigger digit. Materials and Methods: A retrospective analysis was performed on a total of 74 patients with adult idiopathic CTS accompanied with trigger digit admitted to and treated at the Hand Surgery Department of Ningbo No. 6 Hospital from January 1, 2017 to December 31, 2019. Data on patients' gender, age, occupation, course of the disease, menstruation, surgeries, examination-related information, complications, treatment methods, and prognoses during follow-up were recorded and subsequently used to analyze the pathogeneses, clinical characteristics, and treatment. Results: A total of 74 patients (72 females and 2 males) were included. Among female patients, 51 were postmenopausal and 18 were non-postmenopausal. There were 101 fingers with trigger digit, including 14 patients with trigger digit in both hands, and 115 wrists affected by the CTS. The average course of CTS was 34.5 ± 49.3 months, and that of trigger digit was 10.5 ± 22.4 months. Seventy had both trigger digit and CTS in one hand, while among patients with both hands involved, only 4 had trigger digit or CTS in one hand. Eighty-nine fingers underwent A1 pulley release, and 104 hands underwent carpal tunnel surgery, with steroids being injected under the adventitia of the median nerve during the surgery. All patients who underwent surgeries had I/A-healed incisions, and 14 of them had obvious synovial hyperplasia observed in the carpal tunnel and flexor tendon sheath during surgeries. Follow-up visits, which lasted 3 to 35 months, had an average duration of 1.34 years and included 72 patients. In 63 patients (63/72), the syndrome of tenosynovitis and numbness disappeared and normal hand functions were restored; in 6 patients, the numbness in hands greatly improved and normal hand functions were almost completely restored, while no improvement in numbness of hands and limited hand functions were still observed in 3 patients. Conclusion: CTS accompanied with trigger digit was more common in postmenopausal females, and the course of CTS was longer than that of trigger digit. CTS and trigger digit were more likely to simultaneously occur in the same hand, while some patients might not have obvious synovial hyperplasia in the carpal tunnel. Surgeries were effective in severe cases.

Anterior cervical transpedicular screw fixation system in subaxial cervical spine: A finite element comparative study.

Multilevel cervical corpectomy has raised the concern among surgeons that reconstruction with the anterior cervical screw plate system (ACSPS) alone may fail eventually. As an alternative, the anterior cervical transpedicular screw (ACTPS) has been adopted in clinical practice. We used the finite element analysis to investigate whether ACTPS is a more reasonable choice, in comparison with ACSPS, after a 2-level corpectomy in the subaxial cervical spine. These 2 types of implantation models with the applied 75 N axial pressure and 1 N • m pure moment of the couple were evaluated. Compared with the intact model, the range of motion (ROM) at the operative segments (C4-C7) decreased by 97.5% in flexion-extension, 91.3% in axial rotation, and 99.3% in lateral bending in the ACTPS model, whereas it decreased by 95.1%, 73.4%, 96.9% in the ACSPS model respectively. The ROM at the adjacent segment (C3/4) in the ACTPS model decreased in all motions, while that of the ACSPS model increased in axial rotation and flexion-extension compared with the intact model. Compared to the ACSPS model, whose stress concentrated on the interface between the screws and the titanium plate, the stress of the ACTPS model was well-distributed. There was also a significant difference between the maximum stress value of the 2 models. ACTPS and ACSPS are biomechanically favorable. The stability in reducing ROM of ACTPS may be better and the risk of failure for internal fixator is relatively low compared with ACSPS fixation except for under lateral bending in reconstruction the stability of the subaxial cervical spine after 2-level corpectomy.

Development and validation of apoptosis-related signature and molecular subtype to improve prognosis prediction in osteosarcoma patients.

BACKGROUND: Previous evidence has shown that apoptosis performs integral functions in the tumorigenesis and development of various tumors. Therefore, this study aimed to establish a molecular subtype and prognostic signature based on apoptosis-related genes (ARGs) to understand the molecular mechanisms and predict prognosis in patients with osteosarcoma. METHODS: The GEO and TARGET databases were utilized to obtain the expression levels of ARGs and clinical information of osteosarcoma patients. Consensus clustering analysis was used to explore the different molecular subtypes based on ARGs. GO, KEGG, GSEA, ESTIMATE, and ssGSEA analyses were performed to examine the differences in biological functions and immune characteristics between the distinct molecular subtypes. Then, we constructed an ARG signature by LASSO analysis. The prognostic significance of the ARG signature in osteosarcoma was determined by Kaplan-Meier plotter, Cox regression, and nomogram analyses. RESULTS: Two apoptosis-related subtypes were identified. Cluster 1 had a better prognosis, higher immunogenicity, and immune cell infiltration, as well as a better response to immunotherapy than Cluster 2. We discovered that patients in the high-risk cohort had a lower survival rate than those in the low-risk cohort according to the ARG signature. Furthermore, Cox regression analysis confirmed that a high risk score independently acted as an unfavorable prognostic marker. Additionally, the nomogram combining risk scores with clinical characteristics can improve prediction efficiency. CONCLUSION: We demonstrated that patients suffering from osteosarcoma may be classified into two apoptosis-related subtypes. Moreover, we developed an ARG prognostic signature to predict the prognosis status of osteosarcoma patients.

Propeller perforator flaps from the dorsal digital artery perforator chain for repairing soft tissue defects of the finger.

BACKGROUND: When restoring the appearance and function of the fingers, hand surgeons face a challenge in choosing a suitable surgical method to repair finger skin defects. METHODS: In this study, we designed a long elliptical flap based on a propeller perforator flap and located slightly toward the dorsal lateral aspect of the finger. The flap with a pedicle consisting of the dorsal perforator of the distal digital artery and dorsal digital artery perforator chain is rotated to cover a large wound on the distal end. From December 2014 to December 2017, 10 patients with finger soft tissue defects were treated with the propeller perforator flap described in this study. RESULTS: All flaps survived after surgery, and 2 had a transient venous congestion. After a follow-up period of 3 to 12 months, the static two-point discrimination of the flap was 8.06 ± 1.75 mm, and the range of motion was 149.4 ± 12.9°. This designed flap can span several angiosomes supplied by the perforators. Due to the inclusion of a vessel chain between the dorsal digital artery perforators, the length-to-width ratio of the flap can be up to 3:1. CONCLUSIONS: This technique increases the size of flap that can be harvested safely while retaining a reliable blood supply. The present study describes a new method for repairing soft tissue defects of the finger by using the technique of propeller perforator flaps based on dorsal digital artery perforator chains. TRIAL REGISTRATION: The registration number of this study is ChiCTR1800014588; it has been retrospectively registered with Chinese Clinical Trial Registry (chictr.org.cn), 18/11/2019.

A systematic review and meta-analysis approach on diagnostic value of MLH1 promoter methylation for head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the leading histological type among head and neck cancers. Several studies have explored an association between aberrant methylation of MutL homolog-1 (MLH1) promoter and HNSCC risk. We aimed to explore the associations between MLH1 promoter methylation and HNSCC by using a meta-analysis. METHODS: Systematic literature search was conducted among PubMed, Google Scholar, Web of Science, and China National Knowledge Infrastructure, and Wanfang databases to retrieve relevant articles published up to June 30, 2018. A total of 12 studies were included in this meta-analysis (including 717 HNSCC and 609 controls). RESULTS: The results demonstrated that MLH1 promoter methylation was notably higher in patients with HNSCC than in controls (odds ratios [ORs] = 2.52, 95% confidence intervals [CIs] = 1.33-4.79). Besides, MLH1 promoter methylation was not associated with tumor stage, lymph node status, smoking behavior, age, clinical stage, gender, and differentiation grade (all P > .05). The pooled sensitivity and specificity rates of MLH1 methylation for HNSCC were 0.23 (95% CI = 0.12-0.38) and 0.95 (95% CI, 0.82-0.99), respectively. The area under the receiver operating characteristic (ROC) curve was presented as 0.64 (95% CI = 0.60-0.68). CONCLUSION: The results of this meta-analysis suggested that hypermethylation of MLH1 promoter was associated with HNSCC. Methylated MLH1 could be a potential diagnostic biomarker for diagnose of HNSCC.

An RCT study on the feasibility of anterior transpedicular screw fixation in the cervicothoracic junction.

STUDY DESIGN: We evaluated the trajectory and the entry points of anterior transpedicular screws (ATPS) in the cervicothoracic junction (CTJ). OBJECTIVE: This study aimed at investigating the feasibility of ATPS fixation in the CTJ. Application of an ATPS in the lower cervical spine has been reported; however, there were no reports exploring the feasibility of anterior transpedicular screw fixation in the CTJ. METHODS: CT scans were performed in 50 cases and multiplanar reformation was used to measure the related parameters on pedicle axis view at C6-T2. Transverse pedicle angle, outer pedicle width, pedicle axis length, distance transverse intersection point (DtIP), sagittal pedicle angle, anterior vertebral body height, outer pedicle height, and distance sagittal intersection point (DsIP) were measured. The prozone of CTJ was divided into three different regions, which were named as the "manubrium region", the region "above" and "below" the manubrium. The distribution of the trajectory of sagittal pedicle axes was recorded in the three regions and the related data were statistically analyzed. RESULTS: There was no statistical difference in gender (P > 0.05). The transverse pedicle angle decreased from C6 (46.77° ± 2.72°) to T2 (20.62° ± 5.04°). DtIP increased from C6 to T2. DsIP was an average of 7.17 mm. The sagittal pedicle axis lines of the C6 and C7 were located in the region above the manubrium. T1 was mainly in the manubrium region followed by the region above the manubrium. T2 was mainly located in the manubrium region followed by the region below the manubrium. CONCLUSION: Implantation of ATPS at C6, C7, and some T1 is feasible through the low anterior cervical approach, while it is almost impossible to approach T2 that way.

[Application of the pedicle screw in the subaxial cervical spine].

OBJECTIVE: To research the clinical application of lower cervical pedicle screw fixation procedure. METHODS: From September 2011 to July 2013,32 patients underwent posterior pedicle screw-rod system fixation were retrospective analyzed includinig 20 males and 12 females with an average age of 56.4 years old ranging from 21 to 78 years. Among them, 10 patients were traumatic cervical spinal injury, 9 patients were cervical spinal canal tumors, 7 cases were posterior longitudinal ligament ossification of cervical vertebrae, 6 cases were multiple segmental cervical spondylopathy. Preoperatively, X-ray, computed tomography, magnetic resonance imaging and magnetic resonance angiography of the vertebral artery were performed in all patients. After the operation and during the follow-up,X-ray and computed tomography were performed to confirm the pedicle screw position. The accuracy of the pedicle screw placement was evaluated by 4 grades classification from Lee. The spinal cord function was assessed by ASIA impairment scale for traumatic patients and JOA score for non traumatic patients. RESULTS: Totally 144 pedicle screws performed on 32 patients from C3 to C7 involving 132 screws of grade 0,5 screws of grade 1,5 of screws grade 2 and 2 screws of grade 3 according to postoperative CT. There were 12 screws penetrating the pedicle cortex including 8 screws at lateral,2 screws at caudal, 1 screw at medial and 1 screw at cranial. The follow-up time was 12 to 33 months with an average of (21.0±1.5) months. The spinal cord function was not improved in 6 complete cervical spinal cord injury patients,but their paraplegic level descended 1 to 3 segments. Four incomplete cervical spinal cord injury patients' ASIA impairment scale was increased by 1 to 2 grades in average. The JOA score of 22 atraumatic patients increased from preoperative 11.5±0.8 to 15.9±0.6 of postoperative at 6 months (P<0.01). There were no screw loosening,screw pullout and screw-rod breakage. CONCLUSION: The lower cervical pedicle screw fixation can provide excellent 3D stability of the vertebral column. The operation risk and Complication could be minimized by adequate preoperative evaluation for appropriate cases and individual pedicle screw placement. It deserved the clinical expansion.

[Three-dimensional finite-element study on anterior transpedicular screw fixation system of the subaxial cervical spine].

OBJECTIVE: To evaluate the biomechanical effects of the anterior cervical transpedicular-screw system (ACTPS), compared to the anterior cervical screw plate system (ACLP), in the subaxial cervical spine after 2-level corpectomy. METHODS: A verified intact finite element subaxial cervical (C3-C7) model was established and analyzed by Mimics 10.0, Rapidform XOR3, Hypermesh 10.0, CATIA5V19, ANSYS 14.0 softwares based on the CT data (C1-T1) was collected from a 28 years old male volunteer. The axial force of 75 N and moment couple of 1N·m was loaded on the upper surface of C3, which made the model movement in flexion extension, lateral bending, rotating direction, respectively. Then, recorded the range of motion, and compared the results with the in vitro biomechanical experimental data to verify the effectiveness of the model. The ACTPS model and the ACLP model were analyzed using the finite element method. The range of motion at the operation segments (C4-C7), the range of motion at the adjacent segment (C3-C4) and stress distribution under flexion, extension, lateral bending, and axial rotation were calculated, and compared the range of motion with intact model. RESULTS: There were 85,832 elements and 23,612 nodes in the intact model of subaxial cervical spine (C3-C7) in this experiment,and the range of motion of intact model validated with the reported cadaveric experimental data. In ACTPS group the stress was been well-distributed, but the stress concentrated on the interface between screw and the titanium plate in ACLP group. There were obvious differences of the maximum stress value between the two groups. The range of motion of fixed segments in ACTPS group was smaller than ACLP group, however adjacent segment range of motion showed no significant difference. Compared with the intact group, the range of motion in flexion extension, lateral flexion, rotation direction was decreased respectively about 25°, 20° and 8°, the range of motion at adjacent segment (C3-C4) was correspondingly compensated about 0.3°, 3° and 0.1°. CONCLUSIONS: ACTPS is better than ACLP in terms of biomechanical properties. It offers rigid stability, and may be more suitable for reconstruction stability of 2-level and more than 2 levels corpectomy in the subaxial cervical spine. Meanwhile, the risk of fracture of ACTPS system is lower than that of the ACLP system.