Successful treatment of a B/T MPAL patient by chemo-free treatment with venetoclax, azacitidine, and blinatumomab.

B/T mixed phenotype acute leukemia (MPAL), which represents only 2-3% of all MPAL cases, is classified as a high-risk leukemia subtype. Adults diagnosed with B/T MPAL have a notably low 3-year survival rate, estimated at 20-40%. The rarity and undercharacterization of B/T MPAL present substantial challenges in identifying an optimal treatment protocol. This report aims to shed light on this issue by presenting a case in which a patient with a complex karyotype was treated using a combination of venetoclax, azacitidine, and blinatumomab. This novel, chemo-free regimen resulted in the patient achieving both hematologic and molecular complete remission, with no severe organ or hematological toxicity observed. Notably, the patient continued to maintain molecular remission for 1 year following the transplantation. Based on these findings, the combination of venetoclax, azacitidine, and blinatumomab could be considered a potential therapeutic approach for B/T MPAL patients, meriting further investigation.

Preclinical study and first-in-human imaging of [18F]FAP-2286, and comparison with 2-[18F]FDG PET/CT in various cancer patients.

PURPOSE: Fibroblast-activated protein (FAP) is highly expressed in cancer-associated fibroblasts (CAFs) of many solid cancers, but low or absent in normal tissues. Our study aimed to develop a novel FAP-specific tracer, namely [18F]FAP-2286, and evaluated its performance in comparison with well-established agents such as [18F]FAPI-42 and [68Ga]Ga-FAP-2286 in preclinical research, as well as 2-[18F]FDG in pilot clinical study. METHODS: [18F]FAP-2286 was manually synthesized in accordance with Good Manufacturing Practice (GMP). Subsequent investigations encompassed cell uptake, competitive binding affinity, internalization and efflux assays using HT-1080hFAP cell lines. PET imaging and biodistribution studies were conducted in HEK-293ThFAP, A549hFAP, HT-1080hFAP tumor-bearing mice as well as HEK-293T, A549 and HT-1080 control groups. Furthermore, clinical evaluation of [18F]FAP-2286 was performed in fifteen patients with various cancers compared to 2-[18F]FDG PET. RESULTS: The radiolabeling yield of [18F]FAP-2286 was 30.53 ± 5.20%, with a radiochemical purity exceeding 97%. In cell assays, [18F]FAP-2286 showed specific uptake, high internalization fraction and low cellular efflux. Rapid tumor uptake and satisfactory tumor retention was observed on micro-PET imaging and cancer patients. Meanwhile, the clinical research demonstrated that [18F]FAP-2286 may represent an alternative for low glucose-metabolism malignant tumors PET imaging such as gastric cancers. CONCLUSION: [18F]FAP-2286 showed superior imaging quality including rapid and high target uptake and satisfactory retention in both tumor-bearing mice and cancer patients. It may emerge as a promising candidate for early or delayed phase imaging and 2-[18F]FDG non-avid cancers PET scan.

First-in-human study of PSMA-targeting agent, [18F]AlF-P16-093: dosimetry and initial evaluation in prostate cancer patients.

PURPOSE: This is a first-in-human study to evaluate the radiation dosimetry of a new prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical, [18F]AlF-P16-093, and also initial investigation of its ability to detect PSMA-positive tumors using PET scans in a cohort of prostate cancer (PCa) patients. METHODS: The [18F]AlF-P16-093 was automatically synthesized with a GE TRACERlab. A total of 23 patients with histopathologically proven PCa were prospectively enrolled. Dosimetry and biodistribution study investigations were carried out on a subset of six (6) PCa patients, involving multiple time-point scanning. The mean absorbed doses were estimated with PMOD and OLINDA software. RESULTS: [18F]AlF-P16-093 was successfully synthesized, and radiochemical purity was > 95%, and average labeling yield was 36.5 ± 8.3% (decay correction, n = 12). The highest tracer uptake was observed in the kidneys, spleen, and liver, contributing to an effective dose of 16.8 ± 1.3 µSv/MBq, which was ~ 30% lower than that of [68Ga]Ga-P16-093. All subjects tolerated the PET examination well, and no reportable side-effects were observed. The PSMA-positive tumors displayed rapid uptake, and they were all detectable within 10 min, and no additional lesions were observed in the following multi-time points scanning. Each patient had at least one detectable tumor lesion, and a total of 356 tumor lesions were observed, including intraprostatic, lymph node metastases, bone metastases, and other soft tissue metastases. CONCLUSIONS: We report herein a streamlined method for high yield synthesis of [18F]AlF-P16-093. Preliminary study in PCa patients has demonstrated its safety and acceptable radiation dosimetry. The initial diagnostic study indicated that [18F]AlF-P16-093 PET/CT is efficacious and potentially useful for a widespread application in the diagnosis of PCa patients.

Predictive value of intraoperative contrast-enhanced ultrasound in functional recovery of non-traumatic cervical spinal cord injury.

OBJECTIVES: To evaluate the ability of intraoperative CEUS to predict neurological recovery in patients with degenerative cervical myelopathy (DCM). METHODS: Twenty-six patients with DCM who underwent laminoplasty and intraoperative ultrasound (IOUS) were included in this prospective study. The modified Japanese Orthopaedic Association (mJOA) scores and MRI were assessed before surgery and 12 months postoperatively. The anteroposterior diameter (APD), maximum spinal cord compression (MSCC), and area of signal changes in the cord at the compressed and normal levels were measured and compared using MRI and IOUS. Conventional blood flow and CEUS indices (time to peak, ascending slope, peak intensity (PI), and area under the curve (AUC)) at different levels during IOUS were calculated and analysed. Correlations between all indicators and the neurological recovery rate were evaluated. RESULTS: All patients underwent IOUS and intraoperative CEUS, and the total recovery rate was 50.7 ± 33.3%. APD and MSCC improved significantly (p < 0.01). The recovery rate of the hyperechoic lesion group was significantly worse than that of the isoechoic group (p = 0.016). 22 patients were analysed by contrast analysis software. PI was higher in the compressed zone than in the normal zone (24.58 ± 3.19 versus 22.43 ± 2.39, p = 0.019). ΔPI compress-normal and ΔAUC compress-normal of the hyperechoic lesion group were significantly higher than those of the isoechoic group (median 2.19 versus 0.55, p = 0.017; 135.7 versus 21.54, p = 0.014, respectively), and both indices were moderately negatively correlated with the recovery rate (r = - 0.463, p = 0.030; r = - 0.466, p = 0.029). CONCLUSIONS: Signal changes and microvascular perfusion evaluated using CEUS during surgery are valuable predictors of cervical myelopathy prognosis. CLINICAL RELEVANCE STATEMENT: In the spinal cord compression area of degenerative cervical myelopathy, especially in the hyperechoic lesions, intraoperative CEUS showed more significant contrast agent perfusion than in the normal area, and the degree was negatively correlated with the neurological prognosis. KEY POINTS: • Recovery rates in patients with hyperechoic findings were lower than those of patients without lesions detected during intraoperative ultrasound. • The peak intensity of CEUS was higher in compressed zones than in the normal parts of the spinal cord. • Quantitative CEUS comparisons of the peak intensity and area under the curve at the compressed and normal levels of the spinal cord revealed differences that were inversely correlated to the recovery rate.

An innovative approach to assess spinal canal expansion following French-door cervical laminoplasty by intraoperative ultrasonography.

OBJECTIVE: To investigate the feasibility and effectiveness of applying intraoperative ultrasound (IOUS) to evaluate spinal canal expansion in patients undergoing French-door cervical laminoplasty (FDCL). MATERIALS AND METHODS: Twenty-five patients who underwent FDCL for multilevel degenerative cervical myelopathy were prospectively recruited. Formulae describing the relationship between laminoplasty opening angle (LOA) and laminoplasty opening size, the increase in sagittal canal diameter and the spinal canal area were deduced with trigonometric functions. The LOA was measured with IOUS imaging during surgery, and other spinal canal parameters were assessed. Actual spinal canal enlargement was verified on postoperative CT images. Linear correlation analysis and Bland‒Altman analysis were used to evaluate correlation and agreement between the intraoperative and postoperative measurements. RESULTS: The LOA at C5 measured with IOUS was 27.54 ± 3.12°, and it was 27.23 ± 3.02° on postoperative CT imaging. Linear correlation analysis revealed a significant correlation between IOUS and postoperative CT measurements (r = 0.88; p < 0.01). Bland-Altman plots showed good agreement between these two methods, with a mean difference of 0.30°. For other spinal canal expansion parameter measurements, correlation analysis showed a moderate to a high degree of correlation (p < 0.01), and Bland-Altman analysis indicated good agreement. CONCLUSION: In conclusion, during the French-door cervical laminoplasty procedure, application of IOUS can accurately evaluate spinal canal expansion. This innovative method may be helpful in improving surgical accuracy by enabling the operator to measure and determine canal enlargement during surgery, leading to ideal clinical outcomes and fewer postoperative complications. CLINICAL RELEVANCE STATEMENT: The use of intraoperative ultrasonography to assess spinal canal expansion following French-door cervical laminoplasty may improve outcomes for patients undergoing this procedure by providing more accurate measurements of spinal canal expansion. KEY POINTS: • Spinal canal expansion after French-door cervical laminoplasty substantially influences operative prognosis; insufficient or excessive lamina opening may result in unexpected outcomes. • Prediction of spinal canal expansion during surgery was previously impracticable, but based on this study, intraoperative ultrasonography offers an innovative approach and strongly agrees with postoperative CT measurement. • Since this is the first research to offer real-time canal expansion guidance for cervical laminoplasty, it may improve the accuracy of the operation and produce ideal clinical outcomes with fewer postoperative complications.

Identification of novel gene signatures and immune cell infiltration in intervertebral disc degeneration using bioinformatics analysis.

Background: Intervertebral disc degeneration (IDD) is the leading cause of lower back pain, and an overall understanding of the molecular mechanisms related to IDD is still lacking. The purpose of this study was to explore gene signatures and immune cell infiltration related to IDD via bioinformatics analysis. Methods: A total of five expression profiles of mRNA and non-coding RNA were downloaded from the Gene Expression Omnibus (GEO) database. The potentially involved lncRNA/circRNA-miRNA-mRNA networks and protein-protein interaction networks were constructed by miRNet, circBank, STRING, and the Cytoscape database. Gene ontology, Kyoto Encyclopaedia of Genes and Genomes Analysis, Gene Set Enrichment Analysis, Gene Set Variation Analysis, Immune Infiltration Analysis, and Drug-Gene Interaction were used to analyse the top 20 hub genes. RT-qPCR was conducted to confirm the 12 differential expressions of genes both in the nucleus pulposus and annulus fibrosus tissues Results: There were 346 differentially expressed mRNAs, 12 differentially expressed miRNAs, 883 differentially expressed lncRNAs, and 916 differentially expressed circRNAs in the GEO database. Functional and enrichment analyses revealed hub genes associated with platelet activation, immune responses, focal adhesion, and PI3K-Akt signalling. The apoptotic pathway, the reactive oxygen species pathway, and oxidative phosphorylation play an essential role in IDD. Immune infiltration analysis demonstrated that the Treg cells had significant infiltration, and three levels of immune cells, including dendritic cells, Th2 cells, and tumour-infiltrating lymphocytes, were inhibited in IDD. Drug-gene interaction analysis showed that COL1A1 and COL1A2 were targeted by collagenase clostridium histolyticum, ocriplasmin, and PDGFRA was targeted by 66 drugs or molecular compounds. Finally, 24 cases of IDD tissues and 12 cases of normal disc tissues were collected, and the results of RT-qPCR were consistent with the bioinformatics results. Conclusion: Our data indicated that the 20 hub genes and immune cell infiltration were involved in the pathological process of IDD. In addition, the PDGFRA and two potential drugs were found to be significant in IDD development.

Identification of immunodiagnostic blood biomarkers associated with spinal cord injury severity.

Blood always shows some immune changes after spinal cord injury (SCI), and detection of such changes in blood may be helpful for diagnosis and treatment of SCI. However, studies to date on blood immune changes after SCI in humans are not comprehensive. Therefore, to obtain the characteristics of blood immune changes and immunodiagnostic blood biomarkers of SCI and its different grades, a human blood transcriptome sequencing dataset was downloaded and analyzed to obtain differentially expressed immune-related genes (DEIGs), related functions and signaling pathways related to SCI and its various grades. Characteristic biomarkers of SCI and its different grades were identified by using weighted gene coexpression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) logistic regression. Expression of biomarkers was verified through experiments. The area under the curve (AUC) of biomarkers was calculated to evaluate their diagnostic value, and differences in immune cell content were examined. In this study, 17 kinds of immune cells with different contents between the SCI group and healthy control (HC) group were identified, with 7 immune cell types being significantly increased. Differences in the content of immune cells between different grades of SCI and the HC group were also discovered. DEIGs were identified, with alteration in some immune-related signaling pathways, vascular endothelial growth factor signaling pathways, and axon guidance signaling pathways. The SCI biomarkers identified and those of American Spinal Injury Society Impairment Scale (AIS) A and AIS D of SCI have certain diagnostic sensitivity. Analysis of the correlation of immune cells and biomarkers showed that biomarkers of SCI, AIS A grade and AIS D grade correlated positively or negatively with some immune cells. CKLF, EDNRB, FCER1G, SORT1, and TNFSF13B can be used as immune biomarkers for SCI. Additionally, GDF11and HSPA1L can be used as biomarkers of SCI AIS A grade; PRKCA and CMTM2 can be used as biomarkers of the SCI AIS D grade. Detecting expression of these putative biomarkers and changes in related immune cells may be helpful for predicting the severity of SCI.

Enhanced H2S Gas-Sensing Performance of Ni-Doped ZnO Nanowire Arrays.

Ni-doped ZnO nanowire arrays (Ni-ZnO NRs) with different Ni concentrations are grown on etched fluorine-doped tin oxide electrodes by the hydrothermal method. The Ni-ZnO NRs with a nickel precursor concentration of 0-12 at. % are adjusted to improve the selectivity and response of the devices. The NRs' morphology and microstructure are investigated by scanning electron microscopy and high-resolution transmission electron microscopy. The sensitive property of the Ni-ZnO NRs is measured. It is found that the Ni-ZnO NRs with an 8 at. % Ni precursor concentration have high selectivity for H2S and a large response of 68.9 at 250 °C compared to other gases including ethanol, acetone, toluene, and nitrogen dioxide. Their response/recovery time is 75/54 s. The sensing mechanism is discussed in terms of doping concentration, optimum operating temperature, gas type, and gas concentration. The enhanced performance is related to the regularity degree of the array and the doped Ni3+ and Ni2+ ions, which increases the active sites for oxygen and target gas adsorption on the surface.

Increased blood flow of spinal cord lesion after decompression improves neurological recovery of degenerative cervical myelopathy: an intraoperative ultrasonography-based prospective cohort study.

INTRODUCTION: Surgical decompression is a highly effective therapy for degenerative cervical myelopathy (DCM), but the mechanisms of neurological recovery following decompression remain unclear. This study aimed to evaluate the spinal cord blood flow status after sufficient decompression by intraoperative contrast-enhanced ultrasonography (CEUS) and to analyze the correlation between neurological recovery and postdecompressive spinal cord blood perfusion in DCM. MATERIALS AND METHODS: Patients with multilevel DCM were treated by ultrasound-guided modified French-door laminoplasty using a self-developed rongeur. Neurological function was evaluated using the modified Japanese Orthopaedic Association (mJOA) score preoperatively and at 12 months postoperatively. Spinal cord compression and cervical canal enlargement before and after surgery were assessed by magnetic resonance imaging and computerized tomography. The decompression status was evaluated in real time by intraoperative ultrasonography, while the spinal cord blood flow after sufficient decompression was assessed by CEUS. Patients were categorized as favourable (≥50%) or unfavourable (<50%) recovery according to the recovery rate of the mJOA score at 12 months postoperatively. RESULTS: Twenty-nine patients were included in the study. The mJOA scores were significantly improved in all patients from 11.2±2.1 preoperatively to 15.0±1.1 at 12 months postoperatively, with an average recovery rate of 64.9±16.2%. Computerized tomography and intraoperative ultrasonography confirmed adequate enlargement of the cervical canal and sufficient decompression of the spinal cord, respectively. CEUS revealed that patients with favourable neurological recovery had a greater increased blood flow signal in the compressive spinal cord segment after decompression. CONCLUSIONS: In DCM, intraoperative CEUS can clearly reflect spinal cord blood flow. Patients with increased blood perfusion of the spinal cord lesion immediately after surgical decompression tended to achieve greater neurological recovery.

Inhibiting tau protein improves the recovery of spinal cord injury in rats by alleviating neuroinflammation and oxidative stress.

After spinal cord injury, the concentrations of total and hyperphosphorylated tau in cerebrospinal fluid increase, and levels of both correlate with injury severity. Tau inhibition is considered effective therapy for many central nervous system diseases, including traumatic brain injury and Alzheimer's disease. However, whether it can play a role in the treatment of spinal cord injury remains unclear. In this study, the therapeutic effects of tau inhibition were investigated in a rat model of transection spinal cord injury by injecting the rats with a lentivirus encoding tau siRNA that inhibits tau expression. We found that tau inhibition after spinal cord injury down-regulated the levels of inflammatory mediators, including tumor necrosis factor-α, interleukin-6 and interleukin-1ß. It also led to a shift of activated microglial polarization from the M1 pro-inflammatory phenotype to the M2 anti-inflammatory phenotype, and reduced the amount of reactive oxygen species in the acute phase. Furthermore, the survival of residual neural cells around the injury epicenter, and neuronal and axonal regeneration were also markedly enhanced, which promoted locomotor recovery in the model rats. Collectively, our findings support the conclusion that tau inhibition can attenuate neuroinflammation, alleviate oxidative stress, protect residual cells, facilitate neurogenesis, and improve the functional recovery after spinal cord injury, and thus suggest that tau could be a good molecular target for spinal cord injury therapy.

Comprehensive Analysis of Fibroblast Activation Protein Expression in Interstitial Lung Diseases.

Rationale: Sustained activation of lung fibroblasts and the resulting oversynthesis of the extracellular matrix are detrimental events for patients with interstitial lung diseases (ILDs). Lung biopsy is a primary evaluation technique for the fibrotic status of ILDs, and is also a major risk factor for triggering acute deterioration. Fibroblast activation protein (FAP) is a long-known surface biomarker of activated fibroblasts, but its expression pattern and diagnostic implications in ILDs are poorly defined. Objectives: The present study aims to comprehensively investigate whether the expression intensity of FAP could be used as a potential readout to estimate or measure the amounts of activated fibroblasts in ILD lungs quantitatively. Methods: FAP expression in human primary lung fibroblasts as well as in clinical lung specimens was first tested using multiple experimental methods, including real-time quantitative PCR (qPCR), Western blot, immunofluorescence staining, deep learning measurement of whole slide immunohistochemistry, as well as single-cell sequencing. In addition, FAP-targeted positron emission tomography/computed tomography imaging PET/CT was applied to various types of patients with ILD, and the correlation between the uptake of FAP tracer and pulmonary function parameters was analyzed. Measurements and Main Results: Here, it was revealed, for the first time, FAP expression was upregulated significantly in the early phase of lung fibroblast activation event in response to a low dose of profibrotic cytokine. Single-cell sequencing data further indicate that nearly all FAP-positive cells in ILD lungs were collagen-producing fibroblasts. Immunohistochemical analysis validated that FAP expression level was closely correlated with the abundance of fibroblastic foci on human lung biopsy sections from patients with ILDs. We found that the total standard uptake value (SUV) of FAP inhibitor (FAPI) PET (SUVtotal) was significantly related to lung function decline in patients with ILD. Conclusions: Our results strongly support that in vitro and in vivo detection of FAP can assess the profibrotic activity of ILDs, which may aid in early diagnosis and the selection of an appropriate therapeutic window.

A Novel Method of Making Hinges Using a Newly Designed Sharp Rongeur to Enhance Radiological and Clinical Outcomes in French-Door Cervical Expansive Laminoplasty.

OBJECTIVE: Although the lamina open angle of making hinges is closely related to the outcomes of French-door laminoplasty (FDL) for treatment of cervical spondylosis, there have been no methods to predict the lamina open angle preoperatively as yet. The aim of this study was to investigate the accuracy of predicting the laminal open angle using our newly designed sharp rongeur, and to compare the postoperative outcomes and complications between the methods of making hinges using the newly designed sharp rongeur and the traditional high-speed micro-drill during the FDL. METHODS: This was a single-center retrospective study. Following the approval of the institutional ethics committee, a total of 39 patients (Male: 28; Female: 11) diagnosed with cervical spondylos who underwent FDL in our institution between January 2018 and May 2019 were enrolled. Patients were divided into two groups based on the method of making hinges (sharp rongeur: 22 cases; high-speed micro-drill: 17 cases). The average age at surgery was 59.1 years (range: 16-85 years). The radiological parameters, clinical outcomes, modified Japanese Orthopaedic Association (mJOA) scale score, and the recovery rate of mJOA were recorded and compared between the groups, respectively. The radiological parameters and clinical measurements at pre- and post-operation stages were compared using the paired-sample t-test, the Wilcoxon signed-rank test, and the Friedman's test, and variables in the two groups were analyzed using an unpaired Student's t-test or a Mann-Whitney U test. RESULTS: The average follow-up period was 20.4 months (range: 14.0-25.9 months), the postoperative open angle was 60.13° ± 3.69° in the rongeur group with 22.78° ± 4.34° of angular enlargement, which was significantly lower than that of 68.96° ± 1.00° in the micro-drill group with 32.75° ± 4.22° of angular enlargement (U = 19.000, p < 0.001). The rongeur group showed a higher fusion rate (34.1% vs 14.7%, χ2  = 11.340, p = 0.001), and a lower fracture rate of the lamina (7.8% vs 25.5%, χ2  = 14.185, p < 0.001) at 1-month post-surgery, compared to the micro-drill group. There were no significant differences in the clinical outcomes and postoperative complications between the two groups (p > 0.05), except in the recovery rate of mJOA scores (0.836 ± 0.138 vs 0.724 ± 0.180, U = 115.000, p = 0.042) and neck disability index (NDI) at the final follow-up (7.55 ± 10.65 vs 14.71 ± 8.72, U = 94.000, p = 0.008). CONCLUSIONS: The special sharp rongeur with a tip angle of 20° could be a preferred method to make hinges during FDL, which can predict the laminal open angle accurately and enlarge it to about 23°, thus reducing the fracture rate and accelerating the bony fusion of hinges compared with the outcomes of the traditional micro-drill method.

Transplanting neurofibromatosis-1 gene knockout neural stem cells improve functional recovery in rats with spinal cord injury by enhancing the mTORC2 pathway.

The poor survival and low efficiency of neuronal differentiation limits the therapeutic effects of transplanted neural stem cells in the treatment of spinal cord injury. Neurofibromatosis-1 (NF-1) is a tumor suppressor gene that restricts the rapid and abnormal growth and differentiation of neural cells. In the present study, lentiviral vectors were used to knock out NF-1, Ricotr (the core member of mTORC2) or NF-1+Ricotr in neural stem cells in vitro, and the NF-1, Ricotr or NF-1+Ricotr knockout neural stem cells were transplanted at the lesion site in a rat model of spinal cord injury (SCI). We first demonstrated that targeted knockout of NF-1 had an antiapoptotic effect and improved neuronal differentiation by enhancing the mTORC2/Rictor pathway of neural stem cells in vitro. Subsequently, transplanting NF-1 knockout neural stem cells into the injured site sufficiently promoted the tissue repair and functional recovery of rats with spinal cord injury by enhancing the survival and neuronal differentiation of grafted neural stem cells. Collectively, these findings reveal a prominent role of NF-1 in neural stem cell biology, which is an invaluable step forward in enhancing the benefit of neural stem cell-mediated regenerative cell therapy for spinal cord injury and identifies the transplantation of NF-1 knockout neural stem cells as a promising strategy for spinal cord injury.

Comparative intra- and inter-observer reliability of two methods for evaluating intraoperative ultrasonography-based spinal cord hyperechogenicity intensity in degenerative cervical myelopathy.

OBJECTIVES: During French-door laminoplasty, a linear array transducer of IOUS was used to observe and record the spinal cord decompression. To acquire a higher-reliability method, and compare the in-observer and inter-observer reliability of two methods in evaluating the hyperechoic intensity of spinal cord ultrasound in degenerative cervical myelopathy (DCM). BACKGROUND: The intensity of spinal cord hyperechogenicity is considered as a potential predictor of neurological recovery in DCM after decompression, but the accuracy of gray value ratio (GVR) is affected by many factors. METHODS: Totally 28 patients (20 males and 8 females) who had been followed up for 12 months were included. Their mean age at surgery was 61.2 ± 10.8 years and the average symptom duration was 23.36 ± 22.11 months. The gray values of circles 1, 2 and 3 were recorded as Gcompression, Gnorml and Gsac, respectively. Circle 1 was drawn with the maximum brightness point within the spinal cord as the center, circle 2 with the same area was plotted on the spinal cord with uniform echogenicity, without compression and at least 1 cm away from the circle 1, and circle 3 was drawn on the dorsal dural sac at the same segment as circle 1. GVR was calculated as follows: GVR-A = Gcompression/Gnorml (method A), and GVR-B = Gcompression/Gsac (method B). The in-observer and inter-observer reliabilities of the two methods were compared. It is generally believed a reliability coefficient < 0.40 and > 0.75 indicate poor and good reliability respectively. The images-based GVR-B using this protocol demonstrates higher inter- and intraobserver reliabilities than GVR-A, and can be used as the basis for prognostic prediction and future studies. RESULTS: All examination acquisitions were successfully completed. GVR-A averaged 2.043 (0.318-5.56), and GVR-B averaged 0.578(0.06-1.41). GVR-B has better repeatability of gray value measurement, smaller relative standard deviation (RSD%) (0.298 vs. 0.32) and larger inter-group correlation coefficient compared with GVR-A. The mean value (MD) of the GVR difference calculated by GVR-B between the two clinicians was closer to 0. CONCLUSIONS: For DCM patients routinely using ultrasound for real-time cord visualization during spinal cord decompression by French-door laminoplasty, the images-based GVR-B using this protocol demonstrates better inter- and intraobserver reliabilities compared with GVR-A.

Effect of knee joint weight change on knee function recovery and gait after total knee arthroplasty.

BACKGROUND: Knee osteoarthritis (KOA) is a common disease based on degenerative pathological changes. Total knee arthroplasty (TKA) is an effective treatment for end-stage of KOA. However, only volume adaptation can be achieved with current knee prostheses, and it is difficult to achieve weight adaptation. This study focused on the weight difference of knee joints and initially explored the impact of this change on knee joint functional recovery and gait changes in patients after surgery. METHODS: From October 2015 to June 2019, patients who underwent primary unilateral TKA were enrolled in this prospective cohort study with the same brand of knee prostheses. General data were collected from patients who met the criteria. The resected bone and soft tissues were collected and weighed precisely during TKA, and multivariate regression analysis was used to determine the factors affecting the weight of the removed knee tissues. We compared the weight of excised tissues and the total weight of the knee prosthesis, and the weight difference was defined as the increased weight of the knee joint (IWKJ). All patients were evaluated by HSS score, gait analysis, and affected side knee X-ray at two weeks, three months, and the last follow-up after the operation. To further determine the influence of IWKJ on postoperative functional recovery, the relationship between IWKJ, HSS score, and gait analysis was analyzed by univariate regression. RESULTS: In total, 210 patients were eventually included in observation. All patients underwent postoperative follow-up for no less than two years. Multiple regression analysis showed that the course of the disease, body weight, and kellgren-Larencen stage(K-L stage)of the affected knee joint were independent factors affecting the weight of the removed knee tissues and were positively correlated with it. Univariate analysis showed that IWKJ was negatively correlated with HSS score at two weeks and three months after the operation. In addition, the values of spatiotemporal parameters and knee rotation ROM were negatively correlated with IWKJ two weeks after surgery, while outside food load response was positively correlated with IWKJ. Cadence, knee rotation ROM, and Ankle rotation ROM were negatively correlated with IWKJ, while outside food was positively correlated with IWKJ three months after surgery. At the last follow-up, only the hip rotation ROM was positively correlated with IWKJ. CONCLUSIONS: All Patients underwent TKA had varying degrees of increased knee weight. The increased weight was 298.98 ± 63.77 g. Patients' body weight, K-L staging, and disease duration are important factors that cause differences in resected knee tissue. Three months after the operation, the changes in knee joint weight had a negative correlation with the HSS score, which at the same time, it had varying degrees of linearity with gait parameters. However, the influence of weight diminished over time.

Association of cerebrospinal fluid advanced oxidation protein products levels with early brain injury and prognosis of aneurysmal subarachnoid hemorrhage: A preliminary prospective study.

OBJECTIVES: In this study, we investigated the time course in the cerebrospinal fluid (CSF) advanced oxidation protein products (AOPPs) levels in patients with aneurysmal subarachnoid hemorrhage (aSAH), and ascertained the relationship between the levels of AOPPs and early brain injury (EBI), hydrocephalus and prognosis of patients with aSAH. METHODS: We measured the CSF AOPPs levels in 50 patients with aSAH at 1-3 d, 4-6 d, 7-9 d, and 10-12 d after hemorrhage. The modified Fisher grades, Hunt-Hess grades, CSF IL-6 levels, peripheral blood count of white blood cells, cerebral edema scores and hydrocephalus were used to assess the severity of brain injury. Modified Rankin Scale (mRS) scores were used to assess the prognosis. Patients with mRS scores greater than 2 were considered to have a poor outcome. RESULTS: CSF AOPPs levels were significantly higher in patients with aSAH with poor prognosis, compared to patients with good prognosis and peaked in the early stage. Among patients with aSAH, the levels of CSF AOPPs on days 1-3 were significantly correlated with modified Fisher grades, Hunt-Hess grades, CSF IL-6 levels, peripheral blood count of white blood cells, and cerebral edema scores. Also, in patients with hydrocephalus, early CSF AOPPs levels were significantly elevated. Levels of CSF AOPPs in aSAH patients on days 1-3, 4-6, and 7-9 were independently associated with poor prognosis at the 90-day follow-up, and the optimal area under the curve (AUC) values for CSF AOPPs levels were found on days 1-3. CONCLUSIONS: AOPPs may serve as the potential biomarker to assess the severity of EBI and prognosis in patients with aSAH.

Two new stenosis detection methods of coronary angiograms.

PURPOSE: Coronary angiography is the "gold standard" for diagnosing coronary artery disease. At present, the methods for detecting and evaluating coronary artery stenosis cannot satisfy the clinical needs, e.g., there is no prior study of detecting stenoses in prespecified vessel segments, which is necessary in clinical practice. METHODS: Two vascular stenosis detection methods are proposed to assist the diagnosis. The first one is an automatic method, which can automatically extract the entire coronary artery tree and mark all the possible stenoses. The second one is an interactive method. With this method, the user can choose any vessel segment to do further analysis of its stenoses. RESULTS: Experiments show that the proposed methods are robust for angiograms with various vessel structures. The precision, sensitivity, and [Formula: see text] score of the automatic stenosis detection method are 0.821, 0.757, and 0.788, respectively. Further investigation proves that the interactive method can provide a more precise outcome of stenosis detection, and our quantitative analysis is closer to reality. CONCLUSION: The proposed automatic method and interactive method are effective and can complement each other in clinical practice. The first method can be used for preliminary screening, and the second method can be used for further quantitative analysis. We believe the proposed solution is more suitable for the clinical diagnosis of CAD.

Monitoring the delicate operations of surgical robots via ultra-sensitive ionic electronic skin.

The arrival of surgical robots in high-end medical equipment is a landmark, and the realization of tactile sensation a major challenge in this important cutting-edge research field. Aiming to address this issue, we present ultra-sensitive ionic electronic skin in the form of flexible capacitive pressure sensors, which incorporate multistage bionic microstructures in ion gels for the purpose of monitoring the delicate operations of surgical robots. Significantly, the ionic skin exhibits an ultra-high sensitivity of 9484.3 kPa-1 (<15 kPa), and the sensitivity remains higher than 235 kPa-1 in the wide range of 15-155 kPa. The device has also achieved a detection limit as low as 0.12 Pa or, equivalently, 0.31 mg, fast response within 24 ms, and high robustness (loading/unloading for 5000 cycles without fatigue). The sensor facilitates the challenging task of tele-operated robotic threading, which exceeds the human tactile perception limit when threading a needle. We have also confirmed that ionic skin can be used in robot-assisted invasive surgery, such as incision/resection of tissues and suturing of wounds, providing tactile information to surgeons to improve operation success rates. The flexible ionic skin is capable of conforming to the various shapes of robotic manipulators, thus has great promise for applications in robotic dexterous manipulation, prosthetics and human-machine interfaces.

The protective effect of quercetin on macrophage pyroptosis via TLR2/Myd88/NF-κB and ROS/AMPK pathway.

AIMS: Pyroptosis is a pro-inflammatory form of programmed cell death, which plays a vital role in the development of inflammatory diseases. As a natural flavonoid, quercetin has been shown to possess anti-inflammatory activity, but its effects on macrophage pyroptosis is still unclear. Therefore, this study aims to investigate the effects of quercetin on macrophage pyroptosis and the underlying mechanism. MATERIAL AND METHODS: LPS/ATP treatment was used to induce THP-1 macrophage pyroptosis. Cell counting kit-8 (CCK-8) assay was used to evaluate cell viability. Scanning electron microscope (SEM) was used to detect cell morphology. Hoechst/propidium iodide (PI) staining and lactate dehydrogenase (LDH) assay were performed to evaluate the cell membrane integrity. The expression of key components and effectors of nod-like receptors3 (NLRP3) inflammasome were examined by real-time PCR and western blot. Immunofluorescence staining was used to detect reactive oxygen species (ROS) level and P65 nuclear translocation. KEY FINDINGS: Our results showed that quercetin prevented THP-1 macrophage pyroptosis by reducing the expression of NLRP3 and cleaved-caspase1, as well as IL-1ß and N-GSDMD in a concentration dependent manner. Quercetin suppressed NLRP3 inflammasome activation by inhibiting ROS overproduction. Moreover, quercetin inhibited the phosphorylation of P65 and its translocation from cytoplasm into nuclear. In addition, we found that quercetin suppressed the increase of TLR2/Myd88 and p-AMPK induced by LPS/ATP, while both TLR2 and AMPK agonist weakened the inhibitory effect of quercetin on the activity of NLRP3 inflammasome and alleviated the protective effect on macrophages pyroptosis. SIGNIFICANCE: Quercetin possesses a protective effect on macrophages pyroptosis via TLR2/Myd88/NF-κB and ROS/AMPK pathway.

Clinical Utility of F-18 Labeled Fibroblast Activation Protein Inhibitor (FAPI) for Primary Staging in Lung Adenocarcinoma: a Prospective Study.

PURPOSE: The purpose of this study was to compare the primary staging of F-18 labeled fibroblast activation protein inhibitor ([18F]F-FAPI) with that of F-18 labeled fluordesoxyglucose positron emission tomography/computed tomography ([18F]F-FDG PET/CT) in patients with lung adenocarcinoma (LAD). PROCEDURES: We prospectively analyzed the images of LAD patients who underwent [18F]F-FAPI and [18F]F-FDG PET/CT between May 2020 and August 2021. [18F]F-FAPI and [18F]F-FDG uptakes were compared using the paired samples t test, and lesion numbers were compared using the Wilcoxon signed-rank test. RESULTS: Thirty-four LAD patients were evaluated. Patients showed high [18F]F-FAPI uptake in primary lesions (SUVmax 12.54 ± 3.77). Both [18F]F-FAPI and [18F]F-FDG had 100% detection rates for primary tumors. However, [18F]F-FAPI showed higher SUVmax than [18F]F-FDG in lesions of the lymph nodes, pleura, bones, and other tissues (all P ≤ 0.05). Although the absolute uptake values of [18F]F-FAPI in brain lesions were lower than those of [18F]F-FDG (1.56 ± 2.19 vs.7.34 ± 3.54, P < 0.0001), the tumor-to-background (T/B) ratios were significantly higher than those of [18F]F-FDG (9.53 ± 12.07 vs.1.01 ± 0.49, P < 0.0001). Generally, [18F]F-FAPI PET/CT could visualize more total lesions than [18F]F-FDG (554 vs.464, P = 0.003), especially in lymph nodes (258 vs.229, P = 0.039), the brain (34 vs.9, P = 0.002), and pleura (56 vs.30, P = 0.041). However, contrast-enhanced brain magnetic-resonance imaging (MRI) showed more brain lesions than [18F]F-FAPI PET/CT (56 vs.34, P = 0.002). Compared with the [18F]F-FDG-based TNM stage, the [18F]F-FAPI-based TNM stage was upgraded in six patients (17.6%). CONCLUSIONS: [18F]F-FAPI PET/CT showed a very high detection rate for primary LAD. In addition, 18F-FAPI PET/CT demonstrated clearer tumor delineation and more lesions than [18F]F-FDG PET/CT, especially in lymph nodes, the brain, and pleura. Therefore, [18F]F-FAPI had an advantage over [18F]F-FDG for primary staging of LAD. However, brain MRI could identify more and smaller lesions than [18F]F-FAPI PET/CT.