PHF23 promotes NSCLC proliferation, metastasis, and chemoresistance via stabilization of ACTN4 and activation of the ERK pathway.

At present, non-small cell lung cancer (NSCLC) is still one of the leading causes of cancer-related deaths. Chemotherapy remains the standard treatment for NSCLC. However, the emergence of chemoresistance is one of the major obstacles to lung cancer treatment. Plant homologous structural domain finger protein 23 (PHF23) plays crucial roles in multiple cell fates. However, the clinical significance and biological role of PHF23 in NSCLC remain elusive. The Cancer Genome Atlas data mining, NCBI/GEO data mining, and western blotting analysis were employed to characterize the expression of PHF23 in NSCLC cell lines and tissues. Statistical analysis of immunohistochemistry and the Kaplan-Meier Plotter database were used to investigate the clinical significance of PHF23. A series of in vivo and in vitro assays, including assays for colony formation, cell viability, 5-ethynyl-2'-deoxyuridine (EDU incorporation) and Transwell migration, flow cytometry, RT-PCR, gene set enrichment analysis, co-immunoprecipitation analysis, and a xenograft tumor model, were performed to demonstrate the effects of PHF23 on the chemosensitivity of NSCLC cells and to clarify the underlying molecular mechanisms. PHF23 is overexpressed in NSCLC cell lines and tissues. High PHF23 levels correlate with short survival times and a poor response to chemotherapy in NSCLC patients. PHF23 overexpression facilitates cell proliferation, migration and sensitizes NSCLC cells to Cisplatin and Docetaxel by promoting DNA damage repair. Alpha-actinin-4 (ACTN4), as a downstream regulator, interacts with PHD domain of PHF23. Moreover, PHF23 is involved in ACTN4 stabilization by inhibiting its ubiquitination level. These results show that PHF23 plays an important role in the development and progression of NSCLC and suggest that PHF23 may serve as a therapeutic target in NSCLC patients.

Effects of sodium hyaluronate administration on levels of antioxidant enzymes, serum substance P and neuropeptide Y in patients undergoing locking plate fixation for tibial plateau fractures.

Objective: To analyze the effects of sodium hyaluronate administration on the serum levels of antioxidase, substance P (SP), and neuropeptide Y (NPY) in patients undergoing locking plate fixation (LPF) for tibial plateau fractures (TPF). Methods: We retrospectively analyzed the records of 66 patients with TPF who received treatment in the Beijing Chao-yang Hospital[PJMS1][2] from February 2017 to August 2020. According to the treatment records, 33 patients underwent LPF surgery (control-group), and 33 patients underwent LPF plus sodium hyaluronate treatment (observation-group). The levels of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (TAC)), SP and NPY. Results: Seven days after LPF operations, both groups showed lower levels of SOD, CAT, and TAC compared to pre-surgery levels, while levels of SP and NPY were higher. However, the observation group showed higher levels of SOD, CAT, and TAC compared to the control group, and lower levels of SP and NPY in the control group (P<0.05). Conclusion: The treatment of TPF with LPF plus sodium hyaluronate administration has been shown to effectively reduce oxidative stress reactions, improve SP and NPY levels.[PJMS3][4].

Predictive Indicators for Complications of Proximal Humerus Fractures Treated with Locking Plate or Intramedullary Nail Fixation.

OBJECTIVE: The purpose of this study was to evaluate the best placement of calcar screws in proximal humerus fracture surgeries. METHODS: This retrospective cohort study included clinical and radiographic outcomes of 98 patients treated with proximal humerus fracture surgeries between January 2017 and June 2020. Demographic data of patients were obtained from medical records. The surgical and radiographic results were also collected: operation time, blood loss, time to surgery, fibular allograft, disruption of medial region hinge, Neer classification, and recovery of medial support. Patients were allocated into two groups: the locking plate group (n = 65) and the intramedullary nail group (n = 33). In this study, we proposed new predictive indicators, named horizontal ratio (HR) and vertical ratio (VR), to quantify the placement of calcar screws in these two groups. A receiver operating characteristic (ROC) analysis was conducted to display the accuracy of these indicators. Shoulder activity, visual scale analog (VAS) score, and Constant score were performed to evaluate postoperative clinical outcomes at 1 year follow-up. RESULTS: In the multivariate logistic regression analysis, only time to surgery and effective medial support were considered statistically significant factors of postoperative complications (p < 0.05). Significant differences were observed between medial support and postoperative complications both in the locking plate group and the intramedullary nail group (p < 0.05). Only the vertical ratio of locking plate (VRLP) was a statistically significant predictor of postoperative complications (p < 0.05). The area under curve was calculated to assess the predictive value of VRLP, which came to 0.84. In addition, a ROC analysis found quantifiable thresholds of the VR was 0.1713 as measures to avoid postoperative complications in the locking plate fixation. CONCLUSION: In locking plate fixation, the incidence of postoperative complications increased significantly when the VR of calcar screws greater than 0.1713, which was beneficial to surgeons to place calcar screws.

Tibial plateau fractures: three dimensional fracture mapping and morphologic measurements.

PURPOSE: The injury mechanisms and classifications of tibial plateau fractures (TPFs) are still controversial. The aim of this study is to show 3D fracture mapping of different types of tibial plateau fractures. Moreover, combined with Schatzker and ten-segment classification, we aimed to analyze the injury frequency and characteristics of different segments. METHODS: In total, 346 patients with TPFs treated at level I trauma centres from 2017 to 2021 were reviewed. The CT files of the included cases were typed and categorized. 3D reconstruction of TPFs patients' CT files were performed using software. All fracture lines were superimposed on the standard model by the software to create TPFs 3D fracture mapping. RESULTS: This study included 204 male and 142 female patients (average age, 47 years [range, 18 to 83 years]) with a tibial plateau fracture. Using the Schatzker classification, we found 39 type I (11.27%), 103 type II (29.77%), nine type III (2.60%), 71 type IV (20.52%), 52 type V (15.03%), 59 type VI (17.05%) fractures, and 13 others (3.76%). The density areas of fracture lines are mainly located in the ALC and PLC segments (74.3%, 69.1%). In different views, fracture lines of different Schatzker types showed distinct distribution characteristics. CONCLUSIONS: Schatzker classification combined with 3D fracture mapping provides a new presentation of tibial plateau fracture morphology. According to the 3D fracture mapping, different types of TPFs have distinctly different distribution characteristics of fracture lines. There are significant differences between different types of fracture injury segments.

Application of Finite Element Analysis Combined With Virtual Computer in Preoperative Planning of Distal Femoral Fracture.

Background: Distal femoral fractures are increasing with an aging population. The computer-assisted preoperative planning has great potential, but there are no preoperative plans to determine appropriate fixation methods for distal femoral fractures on an individual basis. The aims of this study are: (1) to describe the technique of finite element analysis combined with computer-assisted preoperative planning to determine a fixation method for distal femoral fractures and (2) to evaluate the intra-operative realization of this technology and the clinical outcomes based on it for distal femoral fractures. Materials and Methods: Between January 2017 and January 2020, 31 patients with distal femoral fractures treated by open reduction and internal fixation were included and randomly divided into two groups based on preoperative planning methods: conventional group (n = 15) and computer-assisted group (n = 16). Firstly, how to determine the most appropriate plate and screw length and placement in the preoperative planning of distal femoral fractures was described. The time taken for preoperative planning for different fracture types in the computer-assisted group was then analyzed. Finally, intraoperative and postoperative parameters were compared between the conventional and computer-assisted groups, assessing operative time, intraoperative blood loss, number of intraoperative fluoroscopies, days of hospital stay, Visual Analog Scale for Pain Score (VAS), and Knee Society Score (KSS). Results: Mean total planning time for 33-A, 33-B, and 33-C fractures in computer-assisted group were 194.8 ± 6.49, 163.71 ± 9.22, and 237 ± 5.33 min, respectively. Compared with the conventional group, the patients in the computer-assisted group had less blood loss, fewer fluoroscopic images, and shorter operation time (p < 0.05). However, there was no significant difference in the hospitalization days, KSS score and VAS score between the two groups (p > 0.05). Conclusions: The results of this study show that finite element combined with computer-assisted preoperative planning can effectively help surgeons to make accurate and clinically relevant preoperative planning for distal femoral fractures, especially in the selection of appropriate plate length and screw positioning.

Intra- and inter-observer reliability assessment of widely used classifications and the "Ten-segment classification" of tibial plateau fractures.

BACKGROUND: Ten-segment classification provides a different approach to the evaluation of tibial plateau fractures. The purpose of this study was to assess the intra- and inter-observer reliability of three widely used classification systems (Schatzker, Arbeitsgemeinschaft für Osteosynthesefragen (AO/OTA), and the updated three-column concept (uTCC)) with ten-segment classification in two-dimensional computed tomography (2D-CT) and three-dimensional computed tomography (3D-CT). METHOD: Ninety 2D-CT and 3D-CT scans of patients with tibial plateau fractures were included in this retrospective cohort study. The included data were independently classified by six observers of different years of seniority and were independently observed and classified again after eight weeks. Inter-observer and intra-observer reliability of the four fracture classifications made by the six observers was analyzed using the kappa statistic. Kappa values were interpreted according to the categorical rating by Landis and Koch. RESULTS: When the inter-observer reliability was based on 2D-CT/3D-CT analysis, the mean Kappa values for the Schatzker, AO/OTA, uTCC, and ten-segment classification were 0.64/0.66, 0.56/0.59, 0.53/0.65, and 0.60/0.73, respectively. When intra-observer reliability was based on 2D-CT/3D-CT, the mean Kappa values for the Schatzker, AO/OTA, uTCC, and ten-segment classification were 0.68/0.83, 0.69/0.83, 0.74/0.85, and 0.80/0.91, respectively. CONCLUSIONS: The use of 3D-CT is important for the reliable diagnosis and recognition of tibial plateau fracture features compared to 2D-CT. When using 3D-CT, ten-segment classification showed high intra- and inter-observer agreement.