Development and validation of [18 F]-PSMA-1007 PET-based radiomics model to predict biochemical recurrence-free survival following radical prostatectomy.

PURPOSE: Biochemical recurrence (BCR) following radical prostatectomy (RP) is a significant concern for patients with prostate cancer. Reliable prediction models are needed to identify patients at risk for BCR and facilitate appropriate management. This study aimed to develop and validate a clinical-radiomics model based on preoperative [18 F]PSMA-1007 PET for predicting BCR-free survival (BRFS) in patients who underwent RP for prostate cancer. MATERIALS AND METHODS: A total of 236 patients with histologically confirmed prostate cancer who underwent RP were retrospectively analyzed. All patients had a preoperative [18 F]PSMA-1007 PET/CT scan. Radiomics features were extracted from the primary tumor region on PET images. A radiomics signature was developed using the least absolute shrinkage and selection operator (LASSO) Cox regression model. The performance of the radiomics signature in predicting BRFS was assessed using Harrell's concordance index (C-index). The clinical-radiomics nomogram was constructed using the radiomics signature and clinical features. The model was externally validated in an independent cohort of 98 patients. RESULTS: The radiomics signature comprised three features and demonstrated a C-index of 0.76 (95% CI: 0.60-0.91) in the training cohort and 0.71 (95% CI: 0.63-0.79) in the validation cohort. The radiomics signature remained an independent predictor of BRFS in multivariable analysis (HR: 2.48, 95% CI: 1.47-4.17, p < 0.001). The clinical-radiomics nomogram significantly improved the prediction performance (C-index: 0.81, 95% CI: 0.66-0.95, p = 0.007) in the training cohort and (C-index: 0.78 95% CI: 0.63-0.89, p < 0.001) in the validation cohort. CONCLUSION: We developed and validated a novel [18 F]PSMA-1007 PET-based clinical-radiomics model that can predict BRFS following RP in prostate cancer patients. This model may be useful in identifying patients with a higher risk of BCR, thus enabling personalized risk stratification and tailored management strategies.

The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats.

Bone regeneration and mineralization can be achieved by means of distraction osteogenesis (DO). In the present study, we investigated the effect of stromal cell-derived factor 1 (SDF-1) and vascular endothelial growth factor (VEGF) on the new bone formation during DO in rats. Forty-eight Sprague-Dawley rats were randomized into four groups of 12 rats each. We established the left femoral DO model in rats and performed a mid-femoral osteotomy, which was fixed with an external fixator. DO was performed at 0.25 mm/12 h after an incubation period of 5 days. Distraction was continued for 10 days, resulting in a total of 5 mm of lengthening. After distraction, the solution was locally injected into the osteotomy site, once a day 1 ml for 1 week. One group received the solvent alone and served as the control, and the other three groups were treated with SDF-1, VEGF, and SDF-1with VEGF in an aqueous. Sequential X-ray radiographs were taken two weekly. The regeneration was monitored with the use of micro-CT analysis, mechanical testing, and histology. Radiographs showed accelerated regenerate ossification in the SDF-1, VEGF, and SDF-1 with the VEGF group, with a larger amount of new bone compared with the control group, especially SDF-1 with the VEGF group. Micro-CT analysis and biomechanical tests showed Continuous injection of the SDF-1, VEGF, and SDF-1 with VEGF during the consolidation period significantly increased bone mineral density bone volume, mechanical maximum loading, and bone mineralization of the regenerate. Similarly, the expression of osteogenic-specific genes, as determined by real-time polymerase chain reaction , was significantly higher in SDF-1 with the VEGF group than in the other groups. Histological examination revealed more new trabeculae in the distraction gap and more mature bone tissue for the SDF-1 with the VEGF group. SDF-1 and VEGF promote bone regeneration and mineralization during DO, and there is a synergistic effect between the SDF-1 and VEGF. It is possible to provide a new and feasible method to shorten the period of treatment of DO.

The additional value of 18F-FDG PET/CT imaging in guiding the treatment strategy of non-tuberculous mycobacterial patients.

OBJECTIVES: Non-tuberculous mycobacteria (NTM) infection is an increasing health problem due to delaying an effective treatment. However, there are few data on 18F-FDG PET/CT for evaluating the status of NTM patients. The aim of this study was to investigate the potential value of 18F-FDG PET/CT in guiding the treatment strategy of NTM patients. METHODS: We retrospectively analyzed the cases of 23 NTM patients who underwent 18F-FDG PET/CT. The clinical data, including immune status and severity of NTM pulmonary disease (NTM-PD), were reviewed. The metabolic parameters of 18F-FDG included maximum standardized uptake value (SUVmax), SUVmax of the most FDG-avid lesion (SUVTop), SUVTop/SUVmax of the liver (SURLiver), SUVTop/SUVmax of the blood (SURBlood), metabolic lesion volume (MLV), and total lesion glycolysis (TLG). The optimal cut-off values of these parameters were determined using receiver operating characteristic curves. RESULTS: There were 6 patients (26.09%) with localized pulmonary diseases and 17 patients (73.91%) with disseminated diseases. The NTM lesions had high or moderate 18F-FDG uptake (median SUVTop: 8.2 ± 5.7). As for immune status, the median SUVTop in immunocompromised and immunocompetent patients were 5.2 ± 2.5 and 10.0 ± 6.4, respectively, with a significant difference (P = 0.038). As for extent of lesion involvement, SURLiver and SURBlood in localized pulmonary and disseminated diseases were 1.9 ± 1.1 vs. 3.8 ± 1.6, and 2.7 ± 1.8 vs. 5.5 ± 2.6, respectively, with a significant difference (P = 0.016 and 0.026). Moreover, for disease severity, SUVmax of the lung lesion (SUVI-lung) and SUVmax of the marrow (SUVMarrow) in the severe group were 7.7 ± 4.3 and 4.4 ± 2.7, respectively, significantly higher than those in the non-severe group (4.4 ± 2.0 and 2.4 ± 0.8, respectively) (P = 0.027 and 0.036). The ROC curves showed that SUVTop, SURLiver, SURBlood, SUVI-lung, and SUVMarrow had a high sensitivity and specificity for the identification of immune status, lesion extent, and severity of disease in NTM patients. CONCLUSION: 18F-FDG PET/CT is a useful tool in the diagnosis, evaluation of disease activity, immune status, and extent of lesion involvement in NTM patients, and can contribute to planning the appropriate treatment for NTM.

18F-FAPI-04 Outperforms 18F-FDG PET/CT in Clinical Assessments of Patients with Pancreatic Adenocarcinoma.

Accurate diagnosis and staging are crucial for selecting treatment for patients with pancreatic ductal adenocarcinoma (PDAC). The desmoplastic responses associated with PDAC are often characterized by hypometabolism. Here, we investigated 18F-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in evaluation of PDAC and compared the findings with those obtained using 18F-FDG. Methods: Sixty-two PDAC patients underwent 18F-FAPI-04 PET/CT and 18F-FDG PET/CT. Identification of primary lesions, lymph node (LN) metastasis, and distant metastasis (DM) by these methods was evaluated, and TNM staging was performed. Correlation between SUVmax of the primary lesion and treatment response was explored in patients who received systemic therapy. Results: 18F-FAPI-04 PET/CT identified all patients with PDAC; 18F-FDG PET/CT missed 1 patient. Tracer uptake was higher in 18F-FAPI-04 PET/CT than in 18F-FDG PET/CT in primary tumors (10.63 vs. 2.87, P < 0.0001), LN metastasis (2.90 vs. 1.43, P < 0.0001), and DM (liver, 6.11 vs. 3.10, P = 0.002; peritoneal, 4.70 vs. 2.08, P = 0.015). The methods showed no significant difference in the T staging category, but the N and M values were significantly higher for 18F-FAPI-04 PET/CT than for 18F-FDG PET/CT (P = 0.002 and 0.008, respectively). Thus, 14 patients were upgraded, and only 1 patient was downgraded, by 18F-FAPI-04 PET/CT compared with 18F-FDG PET/CT. A high SUVmax of the primary tumor did not correlate with treatment response for either 18F-FAPI-04 or 18F-FDG. Conclusion: 18F-FAPI-04 PET/CT performed better than 18F-FDG PET/CT in identification of primary tumors, LN metastasis, and DM and in TNM staging of PDAC.

Positive effects of brisk walking and Tai Chi on cognitive function in older adults: An fNIRS study.

Exercise has shown to have beneficial effects on cognition in older adults. The purpose of this study was to investigate the cortical hemodynamic responses during the word-color Stroop test (WCST) prior and after acute walking and Tai Chi exercise by functional near-infrared spectroscopy (fNIRS). Twenty participants (9 males, mean age 62.8 ± 5.2), first underwent a baseline WCST test, after which they took three WCST tests in a randomized order, (a) after sitting rest (control), (b) after 6 minutes performing Tai Chi Quan, and (c) after a bout of 6 minutes brisk walking. During these four WCST tests cortical hemodynamic changes in the prefrontal area were monitored with fNIRS. Both brisk walking and Tai Chi enhanced hemodynamic activity during the Stroop incongruent tasks, leading to improved cognitive performance (quicker reaction time). Brisk walking induced a greater hemodynamic activity in the right dorsolateral prefrontal cortex (DLPFC) and ventrolateral prefrontal cortex (VLPFC) area, whereas Tai Chi induced a greater bilateral hemodynamic activity in the DLPFC and VLPFC areas. The present study provided empirical evidence of enhanced hemodynamic response in task- specific regions of the brain that can be achieved by a mere six minutes of brisk walking or Tai Chi in older adults.

Prefrontal cortical hemodynamics and functional network organization during Tai Chi standing meditation: an fNIRS study.

Introduction: Tai Chi standing meditation (Zhan Zhuang, also called pile standing) is characterized by meditation, deep breathing, and mental focus based on theories of traditional Chinese medicine. The purpose of the present study was to explore prefrontal cortical hemodynamics and the functional network organization associated with Tai Chi standing meditation by using functional near-infrared spectroscopy (fNIRS). Methods: Twenty-four channel fNIRS signals were recorded from 24 male Tai Chi Quan practitioners (54.71 ± 8.04 years) while standing at rest and standing during Tai Chi meditation. The general linear model and the SPM method were used to analyze the fNIRS signals. Pearson correlation was calculated to determine the functional connectivity between the prefrontal cortical sub-regions. The small world properties of the FC networks were then further analyzed based on graph theory. Results: During Tai Chi standing meditation, significantly higher concentrations of oxygenated hemoglobin were observed in bilateral dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), frontal eye field (FEF), and pre-motor cortex (PMC) compared with the values measured during standing rest (p < 0.05). Simultaneously, significant decreases in deoxygenated hemoglobin concentration were observed in left VLPFC, right PMC and DLPFC during Tai Chi standing meditation than during standing rest (p < 0.05). Functional connectivity between the left and right PFC was also significantly stronger during the Tai Chi standing meditation (p < 0.05). The functional brain networks exhibited small-world architecture, and more network hubs located in DLPFC and VLPFC were identified during Tai Chi standing meditation than during standing rest. Discussion: These findings suggest that Tai Chi standing meditation introduces significant changes in the cortical blood flow and the brain functional network organization.

Application of PVC pipes as an adjustable bilateral traction device in lower limb fractures.

OBJECTIVE: To introduce a new type of simple adjustable bilateral bidirectional polyvinyl chloride (PVC) tube traction device and discuss the value of using this device before surgery in patients with lower limb fractures. METHODS: To introduce the manufacturing process of an adjustable bilateral traction device made of PVC pipes. From August 2018 to November 2019, the data of 36 patients with lower limb fractures who were treated with this traction device were retrospectively analysed. The treatment outcomes were analysed, including length of both lower limbs, fracture reduction, lower limb mobility, visual analogue scale (VAS) score, incidence of complications, and patient satisfaction. RESULTS: All patients were able to move the affected limb immediately after using the device. The patient's pain was significantly reduced, they were able to turn over freely during bed rest, and the length of the affected limb was restored to that of the healthy limb. Thirty-four (94.5%) patients were satisfied with the reduction of the fracture end, 2 (5.5%) patients with tibiofibular fractures showed angular displacement of the fractured end and satisfactory reduction after the position of the bone traction needle was adjusted; 7 (19.5%) patients developed deep vein thrombosis of the affected lower limb during traction; there was no decubitus or vascular nerve injury, and the overall complication rate was 25% (9/36). All the patients and their families were satisfied with the results of this treatment. CONCLUSION: The aim of this study is to introduce a new type of traction device. It is advantageous in that it is light weight, low cost, easy to assemble, promotes immediate movement of the affected limb after assembly, improves patient comfort and can be used with a titanium steel needle for MRI examination under traction. In the clinical setting, it has been shown to be suitable for the temporary treatment of patients with lower leg fractures prior to surgery, particularly patients who, for various reasons, require nonsurgical treatment in the short term.

CD73 inhibits titanium particle-associated aseptic loosening by alternating activation of macrophages.

Aseptic inflammation is a major cause of late failure in total joint arthroplasty, and the primary factor contributing to the development and perpetuation of aseptic inflammation is classical macrophage activation (M1 phenotype polarization) induced by wear particles. CD73 (ecto-5'-nucleotidase) is an immunosuppressive factor that establishes an adenosine-induced anti-inflammatory environment. Although CD73 has been shown to suppress inflammation by promoting alternate macrophage activation (M2 phenotype polarization), its role in wear particle-induced aseptic inflammation is currently unknown. Our experiments were based on metabolomic assay results in a mouse model of aseptic loosening, and studied the function of CD73 in vivo and in vitro using a mouse aseptic loosening model and a mouse bone marrow derived macrophage (BMDM) inflammation model. Results show that aseptic loosening (AL) reduces the purine metabolic pathway and decreases the native expression of the metabolite adenosine. In vivo, CD73 expression was low in the bone tissue surrounding the titanium nail and synovial-like interface tissue, while in vitro experiments demonstrated that CD73 knockdown promoted titanium particles-induced aseptic inflammation. CD73 overexpression mitigated the titanium particle-mediated enhancement of LPS-induced M1 polarization while promoting the titanium particle-mediated attenuation of IL-4-induced M2 polarization. In BMDM exposed to titanium particles, CD73 promotes M2 polarization via the p38 pathway. Meanwhile, local injection of recombinant mouse CD73 protein slightly alleviated the progression of AL. Collectively, our data suggest that CD73 alleviates the process of AL, and this function is achieved by promoting alternate activation of macrophages.

Comparison of [18F]-OC PET/CT and contrast-enhanced CT/MRI in the detection and evaluation of neuroendocrine neoplasms.

OBJECTIVES: Gallium-68 (68Ga)-labeled somatostatin analog (SSA) PET imaging has been widely used in clinical practice of neuroendocrine neoplasms (NENs). Compared with 68Ga, 18F has a great practical and economic advantage. Although a few studies have shown the characteristics of [18F] AlF-NOTA-octreotide ([18F]-OC) in healthy volunteers and small NEN patient groups, its clinical value needs further investigation. Herein, this retrospective study aimed to evaluate the diagnostic accuracy of [18F]-OC PET/CT in detecting NENs, as well as to compare it with contrast-enhanced CT/MRI. METHODS: We retrospectively reviewed the data of 93 patients who had undergone [18F]-OC PET/CT and CT or MRI scans. Of these patients, there were 45 patients with suspected NENs for diagnostic evaluation, and 48 patients with pathologically confirmed NENs for detecting metastasis or recurrence. [18F]-OC PET/CT images were evaluated visually and semi-quantitatively by measuring maximum standardized uptake value of tumor (SUVmax), tumor-to-background SUVmax ratio (TBR), and SUVmax of hypophysis (SUVhypophysis). A total of 276 suspected NEN lesions were found in these 93 patients. The results of histopathology or radiographic follow-up served as the reference standard for the final diagnosis. RESULTS: Forty-five patients with suspected NENs were confirmed by histopathological examination via resection or biopsy. [18F]-OC PET/CT showed high radiotracer uptake in the lesions of G1-G3 NENs. [18F]-OC PET/CT showed superior performance with 96.3% of sensitivity, 77.8% of specificity, and 88.9% of accuracy in diagnosing NENs compared to CT/MRI. When cutoffs of SUVmax, TBR, and SUVhypophysis were 8.3, 3.1, and 15.4, [18F]-OC PET/CT had the best equilibrium between sensitivity and specificity for differentiating NEN from non-NEN lesions. For a total of 276 suspected NEN lesions, the sensitivity, specificity, and accuracy of [18F]-OC PET/CT for diagnosis of NENs were 90.5%, 82.1%, and 88.8%, respectively, and were higher than those of CT and MRI. G1 and G2 NENs had higher TBR and lower CT enhancement intensity than G3. The SUVmax and TBR had a positive correlation with CT enhancement intensity in G2 rather than in G1 or G3. CONCLUSIONS: [18F]-OC PET/CT is a promising imaging modality for initial diagnosis and detecting metastasis or postoperative recurrence in NENs.

Different Features of 18F-FAPI, 18F-FDG PET/CT and MRI in the Evaluation of Extrahepatic Metastases and Local Recurrent Hepatocellular Carcinoma (HCC): A Case Report and Review of the Literature.

Background: Recurrence and metastasis are important causes of postoperative death in most HCC patients. Conventional imaging modalities such as 18F-FDG PET/CT and enhanced MRI are still unsatisfactory in evaluating these patients in the clinical setting. PET/CT imaging with a radiolabeled fibroblast activation protein inhibitor (FAPI) has emerged as a new imaging technique for the diagnosis and radiotherapy of malignant tumors. While many studies have focused on the diagnostic accuracy of intrahepatic primary HCC, the evaluation of recurrent and metastatic HCC remains only poorly investigated. Case Presentation: A 71-year-old man with a five-year history of HCC after radical resection underwent 18F-FDG PET/CT due to further surgery for tumor recurrence, which revealed two iso-metabolic lesions in the right peritoneum and a hypo-metabolic lesion in the right liver. 18F-FAPI PET/CT was performed to further complement 18F-FDG PET/CT in the detection of these suspected metastatic lesions. Importantly, multiple diffuse intense radioactivity was shown in the hepatic capsule, suggesting metastatic lesions, but a wedge-shaped elevated 18F-FAPI uptake disorder around the FDG-unavid necrotic lesion after radiofrequency ablation (RFA) demonstrated benign stromal fibrosis. Conclusion: This case suggested that 18F-FAPI may have an advantage over 18F-FDG in detecting peritoneal metastasis even in tiny or early hepatic capsules of HCC, but its false positives due to postoperative stromal fibrosis should be noted. Wedge- or strip-shaped FAPI-avid lesions with sharp edges may be post-treatment stromal fibrosis.

Role of 18F-DCFPyL PET/CT in patients with suspected prostate cancer.

OBJECTIVE: Fluorine-18-2-(3-{1-carboxy-5-[(6-18F-flfluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL), a novel positron emission tomography/computed tomography (PET/CT) radiotracer that binds to the prostate specific membrane antigen (PSMA), is increasingly used for biochemically recurrent prostate cancer diagnostics. However, the 18F-DCFPyL characteristics of suspected prostate cancer (SPCa) have been even more rarely described. Herein, in this retrospective study, we describe the clinical impact of 18F-DCFPyL PET/CT imaging in SPCa. SUBJECTS AND METHODS: We retrospectively evaluated the data of 56 SPCa patients who had undergone 18F-DCFPyL PET/CT studies. These patients were done for primary diagnosis/staging. Positron emission tomography/CT images were analyzed both qualitatively and quantitatively (maximum standardized uptake value (SUVmax) and maximum SUV normalized by lean body mass (SULmax)). Histopathologic diagnosis was taken as reference standard. The optimal cut-off of 18F-DCFPyL was determined using receiver operating characteristic curve (ROC). RESULTS: All the patients were confirmed by histopathological examination via prostatectomy or prostate biopsy. Fluorine-18-DCFPyL PET/CT showed higher radiotracer uptake in prostate cancer than that in non-prostate cancer. When SUVmax 5.0 and SULmax 4.0 were cut-off points for determining prostate cancer, the sensitivity of 18F-DCFPyL was 90%, specificity was 100%, and accuracy was 91.2%. Furthermore, there were highly significant positive correlations between SUVmax, SULmax and serum PSA. On comparison of areas under the curve, no significant difference was seen between SUVmax and SULmax in the sensitivity and specificity of 18F-DCFPyL PET/CT for PCa identification. However, delayed PET/CT did not improved accuracy in the term of uncertain PCa in the initial standard imaging. As for lymph node staging, the negative predictive value of 18F-DCFPyL PET/CT was 100%. CONCLUSION: Fluorine-18-DCFPyL PET/CT is a promising imaging modality for initial diagnosis and preoperative N staging in SPCa.

Concentration Changes of Peripheral Blood Mesenchymal Stem Cells of Sprague Dawley Rats during Distraction Osteogenesis.

OBJECTIVES: To observe the changes in the concentrations of circulating peripheral blood mesenchymal stem cells (PBMSCs) in Sprague Dawley (SD) rats and explore the pattern of changes in PBMSCs during the process of distraction osteogenesis. METHODS: SD rats were randomly divided into the osteotomy with lengthening group (lengthening group), the osteotomy without lengthening group (osteotomy group), and the blank control group (control group). Each group included 24 rats. Percutaneous pinning with external fixation of the left femur was carried out in lengthening group and osteotomy group, but control group received no surgical treatment. On day 5 after operation, continuous traction was carried out at a rate of 0.25 mm/d in lengthening group, while no traction was carried out in osteotomy group. Peripheral blood was collected from all rats on days 1, 3, 7, and 16 after the start of traction. PBMSCs were isolated by density gradient centrifugation. CD105, CD34, and CD45 were selected as cell surface markers. The concentration of PBMSCs was detected by flow cytometry and compared between groups at different time points. X-ray films were taken during and after the operation to observe whether the osteotomy end was pulled and the growth and mineralization of the new bone in the osteogenic area of the femur. Color ultrasound was used to monitor the width of the distraction space, the formation of new bone, and the blood supply of soft tissue around the distraction. RESULTS: All rats were able to tolerate the operation well, and the external fixation was firm and reliable. X-ray showed that, in lengthening group, the distraction space of femur gradually widened and new bone gradually formed in the distraction space; after 8 weeks, the samples were taken out, which showed that the new bone tissue in the lengthened area healed well. In osteotomy group, the average healing time of osteotomy was (7.12 ± 0.78) weeks. Ultrasonic examination showed that after the end of traction, the high echo callus shadow was seen in the traction space, and the blood flow signal was obviously rich at an earlier stage. In lengthening group and osteotomy group, the average concentrations of PBMSCs (3.02% ± 0.87% vs 2.95% ± 0.74%, respectively) were significantly increased in the early stage after osteotomy, and the average concentrations of PBMSCs on days 3, 7, and 16 after the start of traction were 5.34% ± 1.13% vs 3.28% ± 1.22%; 6.41% ± 1.05% vs 3.16% ± 0.92%; and 5.94% ± 1.23% vs 1.48% ± 0.52%, respectively. The concentration of PBMSCs in peripheral blood of lengthening group and osteotomy group was the same at osteotomy stage, and the difference between the two groups was not statistically significant (P > 0.05). After that, compared with lengthening group, the concentration of PBMSCs in osteotomy group gradually decreased and maintained at a certain level; the difference between the two groups was statistically significant (P < 0.05). CONCLUSIONS: Distraction osteogenesis of femur can significantly increase PBMSCs in SD rats and participate in the process of bone formation.

[Establishment of artificial joint aseptic loosening mouse model by cobalt-chromium particles stimulation].

OBJECTIVE: To explore the feasibility of establishment of a artificial joint aseptic loosening mouse model by cobalt-chromium particles stimulation. METHODS: Twenty-four 8-week-old male severe combined immunodeficient (SCID) mice were divided into experimental group ( n=12) and control group ( n=12). The titanium nail was inserted into the tibial medullary cavity of mouse in the two groups to simulate artificial joint prosthesis replacement. And the cobalt-chromium particles were injected into the tibial medullary cavity of mouse in experimental group. The survival of the mouse was observed after operation; the position of the titanium nail and the bone mineral density of proximal femur were observed by X-ray film, CT, and Micro-CT bone scanning; and the degree of dissolution of the bone tissue around the tibia was detected by biomechanical test and histological staining. RESULTS: Two mice in experimental group died, and the rest of the mice survived until the experiment was completed. Postoperative imaging examination showed that there was no obvious displacement of titanium nails in control group, and there were new callus around the titanium nails. In experimental group, there was obvious osteolysis around the titanium nails. The bone mineral density of the proximal tibia was 91.25%±0.67%, and the maximum shear force at the tibial nail-bone interface was (5.93±0.85) N in experimental group, which were significantly lower than those in control group [102.07%±1.87% and (16.76±3.09) N] ( t=5.462, P=0.041; t=3.760, P=0.046). Histological observation showed that a large number of inflammatory cells could be seen around the titanium nails in experimental group, while there was no inflammatory cells, and obvious bone tissue formation was observed in control group. CONCLUSION: The artificial joint aseptic loosening mouse model can be successfully established by cobalt-chromium particles stimulation.

[A comparative study on effectiveness of closed reduction and internal fixation of intertrochanteric fracture assisted with skeletal tractor and traction table].

OBJECTIVE: To investigate the effectiveness and advantages of skeletal tractor in closed reduction and proximal femoral nail antirotation (PFNA) internal fixation of intertrochanteric fracture compared with traction table. METHODS: The clinical data of 86 patients with intertrochanteric fractures, who were treated with closed reduction and PFNA internal fixation between October 2016 and March 2018 and met the selection criteria, was retrospectively analysed. Among them, 44 cases were treated with skeletal tractor (trial group) and 42 cases were treated with traction table (control group). There was no significant difference between the two groups in gender, age, cause of injury, fracture side, AO classification, and degree of osteoporosis ( P>0.05). The preoperative position time, operation time, intraoperative fluoroscopy times, intraoperative blood loss, fracture healing time, intraoperative and postoperative complications, and postoperative Harris score were compared between the two groups. RESULTS: The operation was successfully completed in both groups. Compared with the control group, the patients in the trial group had shorter preoperative position time and operation time, fewer intraoperative fluoroscopy times, and less intraoperative blood loss ( P<0.05). The patients were followed up 12-21 months in trial group (mean, 14.2 months) and 12-22 months in control group (mean, 14.3 months). Venous thrombosis of lower extremity occurred in 8 patients (3 cases of trial group and 5 cases of control group) after operation. Internal fixation failure occurred in 5 patients (2 cases of trial group and 3 cases of control group) during 1 year after operation. All fractures healed except for those with internal fixation failure, the fracture healing time was (11.6±2.9) weeks in trial group and (12.4±3.6) weeks in control group; and there was no significant difference between the two groups ( t=1.250, P=0.214). At 1 year after operation, Harris score of the trial group was 86.2±5.9 and that of the control group was 84.1±6.1. There was no significant difference between the two groups ( t=1.768, P=0.080). CONCLUSION: Compared with traction table, skeletal tractor in closed reduction and PFNA internal fixation of intertrochanteric fracture can significantly shorten the preoperative position time and operation time, reduce the intraoperative fluoroscopy times, improve the operation efficiency, and have similar effectiveness.

Carboxylesterase-Cleavable Biotinylated Nanoparticle for Tumor-Dual Targeted Imaging.

Near-infrared (NIR) nanoprobes with fluorescence "Turn-On" property are advantageous in cancer diagnosis but, to the best of our knowledge, "smart" nanoprobe that simultaneously targets both biotin receptor and carboxylesterase (CES) for HepG2 tumor-dual targeted imaging has not been reported. Methods: Using CBT-Cys click condensation reaction, we rationally designed a "smart" NIR fluorescence probe H2N-Cys(StBu)-Lys(Biotin)-Ser(Cy5.5)-CBT (NIR-CBT) and used it to facilely prepare the fluorescence-quenched nanoparticle NIR-CBT-NP. Results: In vitro results indicated that, after NIR-CBT-NP was incubated with CES for 6 h, its fluorescence was turned "On" by 69 folds. Cell experiments verified that NIR-CBT-NP was uptaken by HepG2 cells via biotin receptor-assisted endocytosis and its fluorescence was turned "On" by intracellular CES hydrolysis. Moreover, NIR-CBT-NP was successfully applied to image both biotin receptor- and CES-overexpressing HepG2 tumors. Conclusion: Fluorescence-quenched nanoparticle NIR-CBT-NP was facilely prepared to actively target biotin receptor-overexpressing HepG2 cancer cells and turn the fluorescence "On" by intracellular CES hydrolysis for tumor-dual targeted imaging. We anticipate that our fluorescence "Turn-On" nanoparticle could be applied for liver cancer diagnosis in clinic in the near future.

Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Predicting the Adverse Effects of Chimeric Antigen Receptor T Cell Therapy in Patients with Non-Hodgkin Lymphoma.

CD19-targeting chimeric antigen receptor (CAR)-T cell therapy has shown great efficacy in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) but has been associated with serious adverse effects, such as cytokine release syndrome (CRS). It has been speculated that NHL baseline disease burden might affect clinical outcome and CRS, but this has not been explored in detail in any previous study. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as measured by fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT), are quantitative indicators of baseline tumor burden. Using FDG PET-CT, we calculated baseline and post-CAR-T cell therapy MTV and TLG in 19 patients with NHL. The median MTV was 72 cm3 (range, .02 to 1137.7 cm3), and the median TLG was 555.9 (range, .011 to 8990.3). After a median follow-up of 5 months (range, 1 to 12 months), the best overall response rate was 79.0%. The baseline MTV and TLG did not differ significantly between patients with response and those without response (P = .62 and .95, respectively). On Cox regression analysis, baseline MTV and TLG were not significantly associated with overall survival (P = .67 and .45, respectively). Patients with mild and moderate CRS (grade 0 to 2) had significantly lower MTV and TLG than those with severe CRS (grade 3 to 4) (P = .008 for MTV comparison, P = .011 for TLG comparison). Using FDG PET-CT, we also demonstrated that CAR-T cell therapy in patients with NHL was associated with pseudoprogression and local immune activation. Our data indicate that patients with higher baseline disease burden have more severe CRS, and that CAR-T cell therapy is associated with lymphoma pseudoprogression and local immune activation.

Particulate and ion forms of cobalt-chromium challenged preosteoblasts promote osteoclastogenesis and osteolysis in a murine model of prosthesis failure.

This study investigated the interactive behavior of the particulate and ion forms of cobalt-chromium (Co-Cr) alloy challenged preosteoblasts during the process of prosthetic implant loosening. Preosteoblasts were challenged with Co-Cr particles or Co(II) ions for 72 h, followed by the proliferation and PCR assays. For in vivo test, a titanium pin was implanted into proximal tibia of SCID mice to mimic knee replacement. Co-Cr particles or Co(II) ion challenged preosteoblasts (5 × 105 ) were intra-articularly injected into the implanted knee. The animals were sacrificed 5 weeks post-op, and the prosthetic knees were harvested for biomechanical pin-pullout testing, histological evaluations, and microCT assessment. In vitro study suggested that Co-Cr particles and Co(II) ions significantly suppressed the proliferation of preosteoblasts in a dose-dependent manner. RT-PCR data on the challenged cells indicated overexpression of receptor activator of nuclear factor kappa-B ligand (RANKL) and inhibited osteoprotegerin (OPG) gene expression. Introduction of the differently challenged preosteoblasts to the pin-implant mouse model resulted in reduced implant interfacial shear strength, thicker peri-implant soft-tissue formation, more TRAP+ cells, lower bone mineral density, and bone volume fraction. In conclusion, both Co-Cr particles and Co(II) ions interfered with the growth, maturation, and functions of preosteoblasts, and provides evidence that the metal ions as well play an important role in effecting preosteoblasts in the pathogenesis of aseptic loosening. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 187-194, 2019.

Post hysteroscopic progesterone hormone therapy in the treatment of endometrial polyps.

OBJECTIVE: To find out the clinical effects of post hysteroscopic progesterone hormone therapy in the treatment of endometrial polyps in terms of clinical outcome and the expression of endometrial Vascular Endothelial Growth Factor (VEGF). METHODS: Ninety-eight patients who were confirmed as endometrial polyp in the hospital from April 2014 and December 2016 were selected and divided into treatment group and a control group using random number table, 49 in each group. Patients in both groups were given hysteroscopic operation. Patients in the treatment group were treated by progesterone hormone drugs after hysteroscopic operation, while patients in the control group were not given progesterone hormone. The changes of menstrual blood volume, menstrual cycle and expression of VEGF were compared between the two groups after treatment, and the recurrence condition, thickness of endometrium and hemoglobin were followed up one year after treatment. RESULTS: The pictorial blood loss assessment chart (PBAC) scores of patients in the two groups had no significant difference before treatment (P>0.05); but the score of the treatment group was much lower than that of the control group. The improvement rate of menstrual cycle of the treatment group was much higher than that of the control group, and the difference had statistical significance (P<0.05). Compared to before treatment, the serum VEGF level of the patients in both groups had a remarkable decline in the 1st, 3rd and 6th month after treatment, and the difference had statistical significance (P<0.05). The difference of the serum VEGF level between the two groups in the 1st and 3rd month after treatment had no statistical significance (P>0.05). The serum VEGF level of the treatment group was notably lower than that of the control group six months after treatment, and the difference had statistical significance (P<0.05). The follow-up results demonstrated that the treatment group had smaller thickness of endometrium and higher level of hemoglobin compared to the control group, and the recurrence rate of the treatment group was lower than that of the control group (P<0.05). CONCLUSION: Post hysteroscopic progesterone hormone therapy has favorable clinical effect in treating endometrial polyps as it can effectively prevent the recurrence of endometrial polyps, relieve the level of hemoglobin and reduce endometrial thickness.

Prospective Study of Closed Reduction of Trochanteric Fractures via a Novel Intraoperative Femoral Fracture Reduction Device: Early Clinical Results.

OBJECTIVE: Traction achieved using an intraoperative femoral fracture reduction device (IFFRD) was compared with that observed using a traction table (TT) for closed reduction of trochanteric fractures and cephalomedullary nail fixation. DESIGN: Prospective cohort study. SETTING: Level 1 trauma center. PATIENTS: One hundred forty-one eligible patients with 141 fractures (Orthopaedic Trauma Association type 31-A1, n = 28; A2, n = 75; and A3, n = 38 cases) were randomized to the IFFRD (n = 73) or TT (n = 68) group. INTERVENTION: The IFFRD was used while the patient was placed on a normal radiolucent operation table with 25-30 degrees elevation of the injured side to allow for antero-posterior and lateral fluoroscopic examination and facilitate entry-point guide wire insertion. MAIN OUTCOME MEASURES: Patient demographics, operative and fluoroscopy duration, quality of fracture reduction, and radiological bone union time were recorded. RESULTS: Patient demographics were similar between groups. Duration of patient positioning was longer in the TT group (P < 0.05); duration of fluoroscopy, fracture reduction, and time to union were comparable. CONCLUSIONS: An IFFRD used with a normal radiolucent operation table decreased patient positioning time, with efficacy comparable to the TT approach for closed reduction of trochanteric fractures. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.