Detection of acetylcholinesterase and butyrylcholinesterase in vitro and in vivo using a new fluorescent probe.

A new fluorescence probe OHPD that could specifically identify acetylcholinesterase/butyrylcholinesterase has been developed and successfully applied to imaging in vivo. Probe OHPD shows significant color change, high selectivity, high sensitivity, and low detection limit for the detection of cholinesterase. Moreover, the real-time imaging in situ indicated that endogenous cholinesterase was mainly present in the yolk sac of zebrafish.

Dual-Nozzle 3D Printed Nano-Hydroxyapatite Scaffold Loaded with Vancomycin Sustained-Release Microspheres for Enhancing Bone Regeneration.

Background: Successful treatment of infectious bone defect remains a major challenge in the orthopaedic field. At present, the conventional treatment for infectious bone defects is surgical debridement and long-term systemic antibiotic use. It is necessary to develop a new strategy to achieve effective bone regeneration and local anti-infection for infectious bone defects. Methods: Firstly, vancomycin / poly (lactic acid-glycolic acid) sustained release microspheres (VAN/PLGA-MS) were prepared. Then, through the dual-nozzle 3D printing technology, VAN/PLGA-MS was uniformly loaded into the pores of nano-hydroxyapatite (n-HA) and polylactic acid (PLA) scaffolds printed in a certain proportion, and a composite scaffold (VAN/MS-PLA/n-HA) was designed, which can not only promote bone repair but also resist local infection. Finally, the performance of the composite scaffold was evaluated by in vivo and in vitro biological evaluation. Results: The in vitro release test of microspheres showed that the release of VAN/PLGA-MS was relatively stable from the second day, and the average daily release concentration was about 15.75 µg/mL, which was higher than the minimum concentration specified in the guidelines. The bacteriostatic test in vitro showed that VAN/PLGA-MS had obvious inhibitory effect on Staphylococcus aureus ATCC-29213. Biological evaluation of VAN/MS-PLA/n-HA scaffolds in vitro showed that it can promote the proliferation of adipose stem cells. In vivo biological evaluation showed that VAN/MS-PLA/n-HA scaffold could significantly promote bone regeneration. Conclusion: Our research shows that VAN/MS-PLA/n-HA scaffolds have satisfying biomechanical properties, effectively inhibit the growth of Staphylococcus aureus, with good biocompatibility, and effectiveness on repairing bone defects. The VAN/MS-PLA/n-HA scaffold provide the clinic with an application prospect in bone tissue engineering.

Comparison of single­nucleus and single­cell transcriptomes in hepatocellular carcinoma tissue.

Single­nucleus RNA sequencing (snRNA­seq) is a method used to analyze gene expression in cells for which isolation is complex, such as those in hepatocellular carcinoma (HCC) tissues. It constitutes an alternative to single­cell RNA sequencing (scRNA­seq) by analyzing the nucleus rather than the whole cell; however, whether it can completely replace scRNA­seq in HCC remains to be clarified. In the present study, scRNA­seq was compared with snRNA­seq in tumor tissue obtained from patients with HCC, using the 10X Genomics Chromium platform. Seurat was also used to process the data and compare the differences between the two sequencing methods in identifying different cell types. In the present study, the transcriptomes of 14,349 single nuclei and 9,504 single cells were obtained from the aforementioned HCC tissue. A total of 21 discrete cell clusters, including hepatocytes, endothelial cells, fibroblasts, B cells, T cells, natural killer cells and macrophages were identified. Notably, a high number of hepatocytes were detected using snRNA­seq, while an increased number of immunocytes were identified in the tumor microenvironment using scRNA­seq. Results of the present study provided a comprehensive image of human HCC at a single­cell resolution. Moreover, results of the present study further demonstrated that snRNA­seq may be adequate in replacing scRNA­seq in certain cases, and snRNA­seq performs at an improved level in hepatocyte sequencing. Combined use of the two sequencing methods may contribute to the study of intercellular interactions.

Anterior cervical plating combined with zero-profile anchored spacer for the treatment of cervical facet dislocation in elderly patients.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of anterior cervical plating combined with zero-profile (Z-P) anchored spacer for the treatment of cervical facet dislocation in elderly patients. METHODS: This is a retrospective study. Twelve elderly patients (from 57 to 77 years old, averaged 65 years) with unilateral or bilateral facet dislocation of sub-axial cervical spine from September 2015 to September 2019 surgically treated at the authors' hospital were enrolled in this study. The patients with osteoporosis or osteopenia were all surgically treated by anterior-only procedure using cervical plating combined with zero-profile anchored spacer after closed manual reduction under general anesthesia and spinal cord monitoring. The operation times (OT), estimated blood loss (EBL), perioperative complications, were recorded. The clinical evaluation included visual analogue scales (VAS) and the American Spinal Injury Association (ASIA) scale. The radiographic evaluation included kyphotic angle (KA) and disc height (DH) and the fusion rate. RESULTS: Anterior discectomy, interbody fusion and fixation were performed in all patients after the disloctions were reduced by manual maneuver. The average OT was 66 minutes, with a range from 45 to 110 minutes. The EBL averaged 42 ml per surgical procedure, with a range from 20 to 60 ml. The VAS, ASIA, KA were improved significantly after surgery (P<0.05). The average follow-up time was 24.2 months, with a range from 12 to 38 months. There were no statistical differences between the immediately post-op KA and KA at the last follow-up (P>0.05). No disc space subsidence was observed statistically (P<0.05) Interbody fusion was obtained in all patients. Two patient experienced slight difficulty in swallowing, which were improved 6 weeks later. There were no hardware failure, no segmental instability, no wound infection or other complications. CONCLUSIONS: Manual reduction with spinal cord monitoring under general anesthesia is a safe and efficient option and the anterior cervical plating combined with Z-P spacer could achieve reliable fixation for the patients with cervical facet dislocation in the elderly patients with osteoporosis or osteopenia.

Estrogen-Related Receptor α: A Significant Regulator and Promising Target in Bone Homeostasis and Bone Metastasis.

Bone homeostasis is maintained with the balance between bone formation and bone resorption, which is involved in the functional performance of osteoblast and osteoclast. Disruption of this equilibrium usually causes bone disorders including osteoporosis, osteoarthritis, and osteosclerosis. In addition, aberrant activity of bone also contributes to the bone metastasis that frequently occurs in the late stage of aggressive cancers. Orphan nuclear receptor estrogen-related receptor (ERRα) has been demonstrated to control the bone cell fate and the progression of tumor cells in bone through crosstalk with various molecules and signaling pathways. However, the defined function of this receptor in bone is inconsistent and controversial. Therefore, we summarized the latest research and conducted an overview to reveal the regulatory effect of ERRα on bone homeostasis and bone metastasis, this review may broaden the present understanding of the cellular and molecular model of ERRα and highlight its potential implication in clinical therapy.

The Thermosensitive Injectable Celecoxib-Loaded Chitosan Hydrogel for Repairing Postoperative Intervertebral Disc Defect.

Percutaneous endoscopic lumbar discectomy has been widely used in clinical practice for lumbar spine diseases. But the postoperative disc re-herniation and inflammation are the main reason for pain recurrence after surgery. The postoperative local defect of the intervertebral disc will lead to the instability of the spine, further aggravating the process of intervertebral disc degeneration. In this work, we successfully synthesized the thermosensitive injectable celecoxib-loaded chitosan hydrogel and investigated its material properties, repair effect, biocompatibility, and histocompatibility in in vitro and in vivo study. In vitro and in vivo, the hydrogel has low toxicity, biodegradability, and good biocompatibility. In an animal experiment, this composite hydrogel can effectively fill local tissue defects to maintain the stability of the spine and delay the process of intervertebral disc degeneration after surgery. These results indicated that this composite hydrogel will be a promising way to treat postoperative intervertebral disc disease in future clinical applications.

Du13 encodes a C2 H2 zinc-finger protein that regulates Wxb pre-mRNA splicing and microRNA biogenesis in rice endosperm.

Amylose content is a crucial physicochemical property responsible for the eating and cooking quality of rice (Oryza sativa L.) grain and is mainly controlled by the Waxy (Wx) gene. Previous studies have identified several Dull genes that modulate the expression of the Wxb allele in japonica rice by affecting the splicing efficiency of the Wxb pre-mRNA. Here, we uncover dual roles for a novel Dull gene in pre-mRNA splicing and microRNA processing. We isolated the dull mutant, du13, with a dull endosperm and low amylose content. Map-based cloning showed that Du13 encodes a C2 H2 zinc-finger protein. Du13 coordinates with the nuclear cap-binding complex to regulate the splicing of Wxb transcripts in rice endosperm. Moreover, Du13 also regulates alternative splicing of other protein-coding transcripts and affects the biogenesis of a subset of microRNAs. Our results reveal an evolutionarily conserved link between pre-mRNA splicing and microRNA biogenesis in rice endosperm. Our findings also provide new insights into the functions of Dull genes in rice and expand our knowledge of microRNA biogenesis in monocots.

Antibiotic-loaded calcium sulfate beads in spinal surgery for patients with spondylodiscitis: a clinical retrospective study.

BACKGROUND: Various surgical techniques for treating spondylodiscitis have been proposed, but the optimal surgical treatment remains controversial. In this study, we propose a new procedure that is implanting antibiotic-loaded calcium sulfate (CS) beads into the disc after debridement using the Quadrant channel combined with percutaneous fixation through a single-stage posterolateral approach for the treatment of spondylodiscitis. Thus, the purpose of this study is to assess the safety and efficacy of this procedure. METHODS: This study collected the data of 32 patients with spine spondylodiscitis and was surgically treated in our department from July 2015 to August 2020. The Demographic data included age, gender, involved segment, and complications were collected. The intra-operative details, results of culture, functional outcome, radiologic outcome, and length of hospital stay, laboratory examination were recorded. RESULTS: The mean age of the 32 patients was 61.1 ± 9.7 years old. The mean operative time was 135.0 ± 30.6 minutes, and the mean blood loss was 243.4 ± 92.1 ml. The positive rate of culture was 72%. The mean Visual analogue scale (VAS) and Oswestry Disability Index (ODI) score significantly improved from 7.5 to 1.6 and from 65% to 10%. Cobb angle was significantly improved and could be maintained at final follow-up. New bone formation was observed in all patients. There were no recurrences of infection in our study. CONCLUSIONS: The posterolateral debridement and percutaneous fixation combined with antibiotic-loaded calcium sulfate beads filling are effective in the treatment of spondylodiscitis in terms of infection control, early mobilization, and recovery.

Detection and imaging of Carbon monoxide releasing Molecule-2 in HeLa cells and zebrafish using a Metal-Free Near-Infrared fluorescent off-on probe.

By incorporating 4-nitrobenzene as the recognition unit into a stable hemicyanine skeleton based on IR 780, a designed near-infrared fluorescent off-on probe DNXI shows excellent analytical performance in real-time monitoring of carbon monoxide releasing molecule-2 (CORM-2) in living HeLa cells and zebrafish without transition metals. The response mechanism of CORM-2 with DNXI may reduce the nitro group to an amino group, followed by 1,6-rearrangement elimination reaction, resulting in the recovery of both color and fluorescence signal. As a result, DNXI shows very low background signal, which is rather desired for achieving sensitive detection of CORM-2. Compared with the existing CORM-2 probes, DNXI shows excellent optical performance in vitro and in vivo, high selectivity and sensitivity to CORM-2, as well as near-infrared fluorescence emission 712 nm, with a low detection limit of 103 nM. More importantly, DNXI is low cytotoxic, cell membrane permeable, and its applicability has been demonstrated for monitoring CORM-2 in living HeLa cells and zebrafish. These superior properties of the probe enable it have great potential to be used in biological systems or in vivo related studies.

Efficient Magnetic Nanocatalyst-Induced Chemo- and Ferroptosis Synergistic Cancer Therapy in Combination with T1-T2 Dual-Mode Magnetic Resonance Imaging Through Doxorubicin Delivery.

Excessive iron ions in cancer cells can catalyze H2O2 into highly toxic •OH and then promote the generation of reactive oxygen species (ROS), inducing cancer ferroptosis. However, the efficacy of the ferroptosis catalyst is still insufficient because of low Fe(II) release, which severely limited its application in clinic. Herein, we developed a novel magnetic nanocatalyst for MRI-guided chemo- and ferroptosis synergistic cancer therapies through iRGD-PEG-ss-PEG-modified gadolinium engineering magnetic iron oxide-loaded Dox (ipGdIO-Dox). The introduction of the gadolinium compound disturbed the structure of ipGdIO-Dox, making the magnetic nanocatalyst be more sensitive to weak acid. When ipGdIO-Dox entered into cancer cells, abundant Fe(II) ions were released and then catalyzed H2O2 into highly toxic OH•, which would elevate cellular oxidative stress to damage mitochondria and cell membranes and induce cancer ferroptosis. In addition, the iRGD-PEG-ss-PEG chain coated onto the nanoplatform was also broken by high expression of GSH, and then, the Dox was released. This process not only effectively inhibited DNA replication but also further activated cellular ROS, making the nanoplatform achieve stronger anticancer ability. Besides, the systemic delivery of ipGdIO-Dox significantly enhanced the T1- and T2-weighted MRI signal of the tumor, endowing accurate diagnostic capability for tumor recognition. Therefore, ipGdIO-Dox might be a promising candidate for developing an MRI-guided chemo- and ferroptosis synergistic theranostic system.

Retropharyngeal Reduction Plate for Atlantoaxial Dislocation: A Cadaveric Test and Morphometric Trajectory Analysis.

OBJECTIVE: To evaluate the placement feasibility and safety of the newly designed retropharyngeal reduction plate by cadaveric test and to perform morphometric trajectory analysis. METHODS: The five cadaveric specimens with intact atlantoaxial joint were enrolled in this study. They were used for simulating the placement process and evaluating the placement feasibility of the retropharyngeal reduction plate. The atlantoaxial dislocation (AAD) of five cadaveric specimens were obtained by proper external force after dissecting ligaments. The retropharyngeal reduction plate was placed on atlantoaxial joint of cadaveric specimens. The X-ray and three-dimensional (3D) spiral CT were used for evaluating the placement safety of retropharyngeal reduction plate. The DICOM data was obtained after 3D spiral CT scanning for the morphometric trajectory analysis. RESULTS: The reduction plates were successfully placed on the atlantoaxial joint of five cadaveric specimens through the retropharyngeal approach, respectively. The X-ray and 3D spiral CT showed the accurate screw implantation and satisfying plate placement. The length of the left/right atlas screw trajectory (L/RAT) was, respectively, 1.73 ± 0.01 cm (LAT) and 1.71 ± 0.02 cm (RAT). The length of odontoid screw trajectory (OST) was 1.38 ± 0.02 cm. The length of the left/right axis screw trajectory (L/RAXT) was, respectively, 1.67 ± 0.02 cm (LAXT) and 1.67 ± 0.01 cm (RAXT). There was no statistical significance between left side and right side in terms of AT and AXT (P > 0.05). The angles of atlas screw trajectory angle (ASTA), axis screw trajectory angle (AXSTA), and odontoid screw trajectory angle (OSTA) were 38.04° ± 2.03°, 56.92° ± 2.66°, and 34.78° ± 2.87°, respectively. CONCLUSION: The cadaveric test showed that the retropharyngeal reduction plate is feasible to place on the atlantoaxial joint, which is also a safe treatment choice for atlantoaxial dislocation. The meticulous preoperative planning of screw trajectory based on individual differences was also vital to using this technique.

Hydrogen sulfide detection and zebrafish imaging by a designed sensitive and selective fluorescent probe based on resorufin.

A new long-wavelength fluorescent probe 1 that could specifically identify H2S has been successfully synthesized and applied for imaging H2S in zebrafish. Probe 1 was readily prepared by featuring nitrobenzene as the recognition unit coupled to resorufin. The fluorescence off-on response is based on the fact that H2S can reduce the nitro group to an amino group, followed by the 1,6-rearrangement-elimination and the release of resorufin. By evaluating the application abilities of probe 1 in vivo and vitro, it is shown that probe 1 has high sensitivity and selectivity to H2S, low background fluorescence interference, with a low detection limit of 17.30 µM. Notably, the occurrence of the reaction can be observed by the naked eye, and the color of the solution changes from yellow to pink. More importantly, it is the first time that using paper chips as carrier to detect H2S, which lays a foundation for the practical application of detecting H2S. The excellent analysis and application capabilities of probe 1 make it an effective tool for further application in practice.

A new near-infrared fluorescence probe synthesized from IR-783 for detection and bioimaging of hydrogen peroxide in vitro and in vivo.

A new near-infrared fluorescence probe was developed and synthesized for detection of hydrogen peroxide (H2O2) in vitro and in vivo. Synthesized from IR-783, the probe DBIS was designed to connect 4-(Bromomethyl)benzeneboronic acid pinacol ester as the recognizing moiety to the stable hemicyanine skeleton. Reaction of probe DBIS with H2O2 would result in the oxidation of phenylboronic acid pinacol ester, and thereby release the near-infrared fluorophore HXIS. The background signal of probe DBIS is very low, which is necessary for sensitive detection. Compared with the existing probes for detecting H2O2, the proposed probe DBIS shows excellent optical performance in vitro and in vivo, high selectivity, high sensitivity and good water solubility, as well as near-infrared fluorescence emission 708 nm, with a low detection limit of 0.12 µM. Furthermore, probe DBIS is low cytotoxic, cell membrane permeable, and its applicability has been shown to visualize endogenous H2O2 in mice. In addition, it is the first time that paper chips have been used as carrier to detect H2O2 through fluorescence signals instead of the traditional liquid phase detection mode of fluorescent probes. These superior characteristics of the probe make it have great application potential in biological systems or in vivo related research.

A new metal-free near-infrared fluorescent probe based on nitrofuran for the detection and bioimaging of carbon monoxide releasing molecule-2 in vivo.

As a stable donor for releasing controlled amounts of CO, carbon monoxide releasing molecule-2 (CORM-2) is a new type of therapeutic drug that contributes to exploring the pathophysiological effects of CO. The accurate detection of CORM-2 in biological systems is of great significance for controlling its dosage as a therapeutic drug and elucidating the reaction mechanisms of CO, but currently there is a lack of metal-free near-infrared fluorescent probes. Herein, a new metal-free near-infrared fluorescent probe based on nitrofuran which could selectively identify CORM-2 was designed and it has been successfully applied in living cells, zebrafish and mice. After reacting with CORM-2, both the color and fluorescence signal of the solution are restored, which is ascribed to the reduction of the nitro group. The spectroscopic probe DXPN shows high sensitivity to CORM-2 with a low detection limit of 87 nM and near-infrared fluorescence emission of 712 nm. Notably, this is the first time that paper chips are being used as a carrier to detect CORM-2 through fluorescence signals instead of the traditional liquid phase detection mode of fluorescent probes. These superior properties of the probe make it a promising and reliable tool for exploring the role played by CORM-2 in biological systems.

Early acute fat embolism syndrome caused by femoral fracture: A case report.

BACKGROUND: Fat embolism syndrome (FES) is a rare complication caused by the presence of fat particles in the microcirculation, which usually occurs within 12-72 h after trauma. At present, there have been few cases of fat embolism presenting within 3 h after trauma. Here, we report a case of femoral fracture complicated with an acute fat embolism caused by a car accident. CASE SUMMARY: A 29-year-old woman with pain, swelling and limited movement of her left lower limb after a car accident was taken by ambulance to our hospital. X-ray examination showed fracture of the middle and lower part of the left femur and fracture of the base of the left fifth metatarsal bone. She was hospitalized and admitted to the orthopedic ward. After the attending doctor performed tibial tubercle bone traction, the patient became confused, followed by respiratory distress. Finally, she was transferred to the intensive care unit. After nearly a month of treatment in the intensive care unit, the patient's cognitive function gradually recovered over 6 mo. CONCLUSION: For patients with early traumatic fractures, young emergency physicians and orthopedics should be aware of the possibility of FES.

Establishment of an Autophagy-Related Clinical Prognosis Model for Predicting the Overall Survival of Osteosarcoma.

PURPOSE: Osteosarcoma is the most common primary and highly invasive bone tumor in children and adolescents. The purpose of this study is to construct a multi-gene expression feature related to autophagy, which can be used to predict the prognosis of patients with osteosarcoma. Materials and methods. The clinical and gene expression data of patients with osteosarcoma were obtained from the target database. Enrichment analysis of autophagy-related genes related to overall survival (OS-related ARGs) screened by univariate Cox regression was used to determine OS-related ARGs function and signal pathway. In addition, the selected OS-related ARGs were incorporated into multivariate Cox regression to construct prognostic signature for the overall survival (OS) of osteosarcoma. Use the dataset obtained from the GEO database to verify the signature. Besides, gene set enrichment analysis (GSEA) were applied to further elucidate the molecular mechanisms. Finally, the nomogram is established by combining the risk signature with the clinical characteristics. RESULTS: Our study eventually included 85 patients. Survival analysis showed that patients with low riskScore had better OS. In addition, 16 genes were included in OS-related ARGs. We also generate a prognosis signature based on two OS-related ARGs. The signature can significantly divide patients into low-risk groups and high-risk groups, and has been verified in the data set of GEO. Subsequently, the riskScore, primary tumor site and metastasis status were identified as independent prognostic factors for OS and a nomogram were generated. The C-index of nomogram is 0.789 (95% CI: 0.703~0.875), ROC curve and calibration chart shows that nomogram has a good consistency between prediction and observation of patients. CONCLUSIONS: ARGs was related to the prognosis of osteosarcoma and can be used as a biomarker of prognosis in patients with osteosarcoma. Nomogram can be used to predict OS of patients and improve treatment strategies.

Analysis of risk factors for C5 nerve root paralysis after posterior cervical decompression.

BACKGROUND: C5 nerve root paralysis is a nonnegligible complication after posterior cervical spine surgery (PCSS). The cause of its occurrence remains controversial. The purpose of this study was to analyse the incidence of and risk factors for C5 nerve root paralysis after posterior cervical decompression. METHODS: We retrospectively analysed the clinical data of 640 patients who underwent PCSS in the Department of Orthopaedics, Affiliated Hospital of Qingdao University from September 2013 to September 2019. According to the status of C5 nerve root paralysis after surgery, all patients were divided into paralysis and normal groups. Univariate and multivariate analyses were used to determine the independent risk factors for C5 nerve root paralysis. A receiver operating characteristic (ROC) curve was used to demonstrate the discrimination of all independent risk factors. RESULTS: Multivariate logistic regression analysis revealed that male sex, preoperative cervical spine curvature, posterior longitudinal ligament ossification, and preoperative C4/5 spinal cord hyperintensity were independent risk factors for paralysis, whereas the width of the intervertebral foramina was an independent protective factor for paralysis. The area under the curve (AUC) values of the T2 signal change at C4-C5, sex, cervical foramina width, curvature and posterior longitudinal ligament ossification were 0.706, 0.633, 0.617, 0.637, and 0.569, respectively. CONCLUSIONS: Male patients with C4-C5 intervertebral foramina stenosis, preoperative C4-C5 spinal cord T2 high signal, combined with OPLL, and higher preoperative cervical spine curvature are more likely to develop C5 nerve root paralysis after surgery. Among the above five risk factors, T2 hyperintensity change in C4-C5 exhibits the highest correlation with C5 paralysis and strong diagnostic power. It seems necessary to inform patients who have had cervical spine T2 hyperintensity before surgery of C5 nerve root paralysis after surgery, especially those with altered spinal cord T2 signals in the C4-C5 segment.

Construction of Two Alternative Polyadenylation Signatures to Predict the Prognosis of Sarcoma Patients.

BACKGROUND: Increasing evidence indicates that alternative polyadenylation (APA) is associated with the prognosis of cancers. METHODS: We obtained gene expression and APA profiles of 259 sarcoma patients from the TCGA dataportal and TC3A database, respectively. The prognostic signatures, clinical nomograms, and regulatory networks were studied by integrated bioinformatics analyses. Then, the immune cell infiltration profile was obtained from the ImmuCellAI. The association between APA-based signature and immune cells was studied. RESULTS: A total of 61 and 38 APA events were identified as overall survival (OS)- and progress free-survival (PFS)-related biomarkers, respectively. Two signatures were generated. The area under the curves (AUC) values of OS signature were 0.900, 0.928, and 0.963 over 2-, 4-, and 6-years, respectively. And the AUC values of PFS signature at 2-, 4-, and 6-years were 0.826, 0.840, and 0.847, respectively. Overall and subgroup analyses indicated that high-risk patients had a worse prognosis than low-risk patients (all p-values < 0.05). In addition, immunomics analyses indicated that there are different patterns of immune cell infiltration between low- and high-risk patients. Furthermore, two clinical-APA nomograms were established and the C-indexes were 0.813 and 0.809 for OS nomogram and PFS nomogram, respectively. Finally, two APA regulatory networks were constructed. FIP1L1-VPS26B was identified as a key regulating relationship and validated in the pan-cancer analyses. CONCLUSION: In this study, we identified prognostic predictors based on APA events with high accuracy for risk stratification in sarcoma patients and uncovered interesting regulatory networks in sarcoma that could be underlying mechanisms. This study not only provides novel potential prognostic biomarkers but promote precision medicine and provide potential novel research interests for immunotherapy.

Microscopic extra-laminar sequestrectomy (MELS) for the treatment of hidden zone lumbar disc herniation: report of the surgical technique, patient selection, and clinical outcomes.

BACKGROUND: The area which located at the medial pedicle, posterior vertebral body and ventral hemilamina is defined as the hidden zone. Surgical management of hidden zone lumbar disc herniation (HZLDH) is technically challenging due to its difficult surgical exposure. The conventional interlaminar approach harbors the potential risk of post-surgical instability, while other approaches consist of complicated procedures with a steep learning curve and prolonged operation time. OBJECTIVE: To introduce microscopic extra-laminar sequestrectomy (MELS) technique for treatment of hidden zone lumbar disc herniation and present clinical outcomes. METHODS: Between Jan 2016 to Jan 2018, twenty one patients (13 males) with HZLDH were enrolled in this study. All patients underwent MELS (19 patients underwent sequestrectomy only, 2 patients underwent an additional inferior discectomy). The nerve root and fragment were visually exposed using MELS. The operation duration, blood loss, intra- and postoperative complications, and recurrences were recorded. The Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and the modified MacNab criteria were used to evaluate clinical outcomes. Postoperative stability was evaluated both radiologically and clinically. RESULTS: The mean follow-up period was 20.95 ± 2.09 (18-24) months. The mean operation time was 32.43 ± 7.19 min and the mean blood loss was 25.52 ± 5.37 ml. All patients showed complete neurological symptom relief after surgery. The VAS and ODI score were significantly improved at the final follow-up compared to those before operation (7.88 ± 0.70 vs 0.10 ± 0.30, 59.24 ± 10.83 vs 11.29 ± 3.59, respectively, p < 0.05). Seventeen patients (81%) obtained an "excellent" outcome and the remaining four (19%) patients obtained a "good" outcome based the MacNab criteria. One patient suffered reherniation at the same level one year after the initial surgery and underwent a transforaminal endoscopic discectomy. No major complications and postoperative instability were observed. CONCLUSIONS: Our observation suggest that MELS is safe and effective in the management of HZLDH. Due to its relative simplicity, it comprises a flat surgical learning curve and shorter operation duration, and overall results in reduced disturbance to lumbar stability.

Detection of Tyrosinase in Real Food Samples and Living Cells by a Novel Near-Infrared Fluorescence Probe.

A new near-infrared fluorescence probe was developed and applied to the fluorescence detection of tyrosinase in real food samples and living cells. The probe (E)-2-(2-(6-((3-hydroxybenzyloxy)carbonylamino)-2,3-dihydro-1H-xanthen-4-yl)vinyl)-3,3-dimethyl-1-propyl-3H-indolium (1) was designed and synthesized by coupling 3-hydroxybenzyl alcohol via carbamate bond with an amino hemicyanine skeleton, based on the high anti-interference ability of 3-hydroxybenzyl alcohol to reactive oxygen species and its binding affinity to tyrosinase. Compared with the existing tyrosinase probes, the proposed probe exhibits superior analytical performance, such as high selectivity, high sensitivity, superior spatiotemporal sampling ability, fluorescence signal switching at 706 nm, and low detection limit of 0.36 U mL-1. More importantly, the probe has been successfully used to monitor tyrosinase in the browning of apple slices for the first time, and the results indicated that the strongest fluorescence intensity could be achieved at 2.5 h to realize precise visual recognition of tyrosinase. Notably, the probe determined tyrosinase in real food samples (apple, banana, cheese, and red wine) with a stable average recovery range of 95.7-108.3% and has been successfully used to monitor tyrosinase in the living B16 cells. The superior properties of the probe make it of great potential use in food nutritional value evaluation and clinical diagnosis of melanin-related diseases.