TRIM21-mediated ubiquitination of PLIN2 regulates neuronal lipid droplet accumulation after acute spinal cord injury.

To investigate the changes in neuronal lipid droplet (LD) accumulation and lipid metabolism after acute spinal cord injury (SCI), we established a rat model of compressive SCI. Oil Red O staining, BODIPY 493/503 staining, and 4-hydroxynonenal immunofluorescence staining were performed to determine overall LD accumulation, neuronal LD accumulation, and lipid peroxidation. Lipidomics was conducted to identify the lipid components in the local SCI microenvironment. We focused on the expression and regulation of perilipin 2 (PLIN2) and knocked down PLIN2 in vivo by intrathecal injection of adeno-associated virus 9-synapsin-short-hairpin RNA-PLIN2 (AAV9-SYN-shPlin2). Motor function was assessed using the Basso-Beattie-Bresnahan score. Proteins that interacted with PLIN2 were screened by immunoprecipitation (IP) and qualitative shotgun proteomics, and confirmed by co-IP. A ubiquitination assay was performed to validate whether ubiquitination was involved in PLIN2 degradation. Oil Red O staining indicated that LDs steadily accumulated after SCI. Fluorescent staining indicated the accumulation of LDs in neurons with increased lipid peroxidation. Lipidomics revealed significant changes in lipid components after SCI. PLIN2 expression significantly increased following SCI, and knockdown of PLIN2 using AAV9-SYN-Plin2 reduced neuronal LD accumulation. This intervention improved the neuronal survival and motor function of injured rats. IP and qualitative shotgun proteomics identified tripartite motif-containing protein 21 (TRIM21) as a direct binding protein of PLIN2, and this interaction was confirmed by co-IP in vitro and immunofluorescence staining in vivo. By manipulating TRIM21 expression, we found it was negatively correlated with PLIN2 expression. In conclusion, PLIN2 is involved in neuronal LD accumulation following SCI. TRIM21 mediated the ubiquitination and degradation of PLIN2 in neurons. Inhibition of PLIN2 enhanced the recovery of motor function after SCI.

The Development of Spinal Endoscopic Ultrasonic Imaging System with an Automated Tissue Recognition Algorithm.

STUDY DESIGN: Preclinical experimental study. OBJECTIVE: To develop an intraoperative ultrasound-assisted imaging device, which could be placed at the surgical site through an endoscopic working channel and which could help surgeon recognition of different tissue types during endoscopic spinal surgery (ESS). SUMMARY OF BACKGROUND DATA: ESS remains a challenging task for spinal surgeons. Great proficiency and experience are needed to perform procedures such as intervertebral discectomy and neural decompression within a narrow channel. The limited surgical view poses a risk of damaging important structures, such as nerve roots. METHODS: We constructed a spinal endoscopic ultrasound system, using a 4-mm custom ultrasound probe, which can be easily inserted through the ESS working channel, allowing up to 10 mm depth detection. This system was applied to ovine lumbar spine samples to obtain ultrasound images. Subsequently, we proposed a two-stage classification algorithm, based on a pretrained DenseNet architecture for automated tissue recognition. The recognition algorithm was evaluated using accuracy and consistency. RESULTS: The probe can be easily used in the ESS working channel and produce clear and characteristic ultrasound images. We collected 367 images for training and testing of the recognition algorithm, including images of the spinal cord, nucleus pulposus, adipose tissue, bone, annulus fibrosus and nerve roots. The algorithm achieved over 90% accuracy in recognizing all types of tissues with a Kappa value of 0.875. The recognition times were under 0.1 s using the current configuration. CONCLUSION: Our system was able to be used in existing ESS working channels and clearly identified at-risk spinal structures in vitro. The pretrained algorithms could identify six intraspinal tissue types accurately and quickly. The concept and innovative application of intraoperative ultrasound in ESS may shorten the learning curve of ESS and improve surgical efficiency and safety.

Screening and diagnosis of cardiovascular disease using artificial intelligence-enabled cardiac magnetic resonance imaging.

Cardiac magnetic resonance imaging (CMR) is the gold standard for cardiac function assessment and plays a crucial role in diagnosing cardiovascular disease (CVD). However, its widespread application has been limited by the heavy resource burden of CMR interpretation. Here, to address this challenge, we developed and validated computerized CMR interpretation for screening and diagnosis of 11 types of CVD in 9,719 patients. We propose a two-stage paradigm consisting of noninvasive cine-based CVD screening followed by cine and late gadolinium enhancement-based diagnosis. The screening and diagnostic models achieved high performance (area under the curve of 0.988 ± 0.3% and 0.991 ± 0.0%, respectively) in both internal and external datasets. Furthermore, the diagnostic model outperformed cardiologists in diagnosing pulmonary arterial hypertension, demonstrating the ability of artificial intelligence-enabled CMR to detect previously unidentified CMR features. This proof-of-concept study holds the potential to substantially advance the efficiency and scalability of CMR interpretation, thereby improving CVD screening and diagnosis.

Hybridization-based discovery of novel quinazoline-2-indolinone derivatives as potent and selective PI3Kα inhibitors.

INTRODUCTION: Phosphatidylinositol 3-kinases (PI3Ks) overexpression can elicit cellular homeostatic dysregulation, which further contributes to tumorigenesis, with PI3Kα emerging as the most prevalent mutant isoform kinase among PI3Ks. Therefore, selective inhibitors targeting PI3Kα have attracted considerable interest in recent years. Molecular hybridization, with the advantage of simplified pharmacokinetics and drug-drug interactions, emerged as one of the important avenues for discovering potential drugs. OBJECTIVES: This study aimed to construct PI3Kα inhibitors by hybridization and investigate their antitumor activity and mechanism. METHODS: 26 quinazoline-2-indolinone derivatives were obtained by molecular hybridization, and their structure-activity relationship was analyzed by MTT, in vitro kinase activity and molecular docking. The biological evaluation of compound 8 was performed by transwell, flow cytometry, laser scanning confocal microscopy, Western blot, CTESA and immunohistochemistry. RESULTS: Here, we employed molecular hybridization methods to construct a series of quinazoline-2-indolinone derivatives as PI3Kα selective inhibitors. Encouragingly, representative compound 8 exhibited a PI3Kα enzymatic IC50 value of 9.11 nM and 10.41/16.99/37.53-fold relative to the biochemical selectivity for PI3Kß/γ/δ, respectively. Moreover, compound 8 effectively suppressed the viability of B16, HCT116, MCF-7, H22, PC-3, and A549 cells (IC50 values: 0.2 µM âˆ¼ 0.98 µM), and dramatically inhibited the proliferation and migration of NSCLC cells, as well as induced mitochondrial apoptosis through the PI3K/Akt/mTOR pathway. Importantly, compound 8 demonstrated potent in vivo anti-tumor activity in non-small cell lung cancer mouse models without visible toxicity. CONCLUSIONS: This study presented a new avenue for the development of PI3Kα inhibitors and provided a solid foundation for novel QHIDs as potential future therapies for the treatment of NSCLC.

Luteolin, a flavone ingredient: Anticancer mechanisms, combined medication strategy, pharmacokinetics, clinical trials, and pharmaceutical researches.

Current pharmaceutical research is energetically excavating the pharmacotherapeutic role of herb-derived ingredients in multiple malignancies' targeting. Luteolin is one of the major phytochemical components that exist in various traditional Chinese medicine or medical herbs. Mounting evidence reveals that this phytoconstituent endows prominent therapeutic actions on diverse malignancies, with the underlying mechanisms, combined medication strategy, and pharmacokinetics elusive. Additionally, the clinical trial and pharmaceutical investigation of luteolin remain to be systematically delineated. The present review aimed to comprehensively summarize the updated information with regard to the anticancer mechanism, combined medication strategies, pharmacokinetics, clinical trials, and pharmaceutical researches of luteolin. The survey corroborates that luteolin executes multiple anticancer effects mainly by dampening proliferation and invasion, spurring apoptosis, intercepting cell cycle, regulating autophagy and immune, inhibiting inflammatory response, inducing ferroptosis, and pyroptosis, as well as epigenetic modification, and so on. Luteolin can be applied in combination with numerous clinical anticarcinogens and natural ingredients to synergistically enhance the therapeutic efficacy of malignancies while reducing adverse reactions. For pharmacokinetics, luteolin has an unfavorable oral bioavailability, it mainly persists in plasma as glucuronides and sulfate-conjugates after being metabolized, and is regarded as potent inhibitors of OATP1B1 and OATP2B1, which may be messed with the pharmacokinetic interactions of miscellaneous bioactive substances in vivo. Besides, pharmaceutical innovation of luteolin with leading-edge drug delivery systems such as host-guest complexes, nanoparticles, liposomes, nanoemulsion, microspheres, and hydrogels are beneficial to the exploitation of luteolin-based products. Moreover, some registered clinical trials on luteolin are being carried out, yet clinical research on anticancer effects should be continuously promoted.

Tissue Identification of Intervertebral Disc Anatomy Using Forward-oriented Ultrasound Endoscopic System: A Feasibility Study.

Minimally invasive surgery is widely used for spine surgery, however the commonly used optical endoscopes cannot identity tissues under surface. In this study, a forward-oriented ultrasound endoscopic system was proposed to detect and identity different types of tissues for surgical approaches. A total of 150 ultrasound image data were collected from 6 types of intervertebral disc tissue using a custom-developed endoscopic probe. The gray-level co-occurrence matrix (GLCM) properties including energy (angular second moment, ASM), contrast, entropy, and homogeneity (inverse difference moment, IDM) were calculated on the acquired ultrasound images, and the single-parameter and combined parameter were applied for tissue classification. The classification accuracies of fibrous ring, nerve roots and bone were 100%, and the overall accuracy for all tissues was 73.33%. The results indicated that the combined parameter method provided more accurate classification output. It demonstrated that the proposed endoscopic ultrasonography system had the potential of identifying different tissues under surface during the endoscopic spine surgery.Clinical Relevance-This study establishes that the forward-oriented ultrasound endoscopic system was feasible to identify different types of tissues under surface during the endoscopic spine surgery.

An MRI-based machine learning radiomics can predict short-term response to neoadjuvant chemotherapy in patients with cervical squamous cell carcinoma: A multicenter study.

BACKGROUND AND PURPOSE: Neoadjuvant chemotherapy (NACT) has become an essential component of the comprehensive treatment of cervical squamous cell carcinoma (CSCC). However, not all patients respond to chemotherapy due to individual differences in sensitivity and tolerance to chemotherapy drugs. Therefore, accurately predicting the sensitivity of CSCC patients to NACT was vital for individual chemotherapy. This study aims to construct a machine learning radiomics model based on magnetic resonance imaging (MRI) to assess its efficacy in predicting NACT susceptibility among CSCC patients. METHODS: This study included 234 patients with CSCC from two hospitals, who were divided into a training set (n = 180), a testing set (n = 20), and an external validation set (n = 34). Manual radiomic features were extracted from transverse section MRI images, and feature selection was performed using the recursive feature elimination (RFE) method. A prediction model was then generated using three machine learning algorithms, namely logistic regression, random forest, and support vector machines (SVM), for predicting NACT susceptibility. The model's performance was assessed based on the area under the receiver operating characteristic curve (AUC), accuracy, and sensitivity. RESULTS: The SVM approach achieves the highest scores on both the testing set and the external validation set. In the testing set and external validation set, the AUC of the model was 0.88 and 0.764, and the accuracy was 0.90 and 0.853, the sensitivity was 0.93 and 0.962, respectively. CONCLUSIONS: Machine learning radiomics models based on MRI images have achieved satisfactory performance in predicting the sensitivity of NACT in CSCC patients with high accuracy and robustness, which has great significance for the treatment and personalized medicine of CSCC patients.

Improved Dynamic Event-Triggered Robust Control for Flexible Robotic Arm Systems with Semi-Markov Jump Process.

In this paper, we investigate the problem of a dynamic event-triggered robust controller design for flexible robotic arm systems with continuous-time phase-type semi-Markov jump process. In particular, the change in moment of inertia is first considered in the flexible robotic arm system, which is necessary for ensuring the security and stability control of special robots employed under special circumstances, such as surgical robots and assisted-living robots which have strict lightweight requirements. To handle this problem, a semi-Markov chain is conducted to model this process. Furthermore, the dynamic event-triggered scheme is used to solve the problem of limited bandwidth in the network transmission environment, while considering the impact of DoS attacks. With regard to the challenging circumstances and negative elements previously mentioned, the adequate criteria for the existence of the resilient H∞ controller are obtained using the Lyapunov function approach, and the controller gains, Lyapunov parameters and event-triggered parameters are co-designed. Finally, the effectiveness of the designed controller is demonstrated via numerical simulation using the LMI toolbox in MATLAB.

Identification and functional analysis of a novel de novo missense mutation located in the initiation codon of LAMP2 associated with early onset female Danon disease.

BACKGROUND: Danon disease is characterized by the failure of lysosomal biogenesis, maturation, and function due to a deficiency of lysosomal membrane structural protein (LAMP2). METHODS: The current report describes a female patient with a sudden syncope and hypertrophic cardiomyopathy phenotype. We identified the pathogenic mutations in patients by whole-exon sequencing, followed by a series of molecular biology and genetic approaches to identify and functional analysis of the mutations. RESULTS: Suggestive findings by cardiac magnetic resonance (CMR), electrocardiogram (ECG), and laboratory examination suggested Danon disease which was confirmed by genetic testing. The patient carried a novel de novo mutation, LAMP2 c.2T>C located at the initiation codon. The quantitative polymerase chain reaction (qPCR) and Western blot (WB) analysis of peripheral blood leukocytes from the patients revealed evidence of LAMP2 haploinsufficiency. Labeling of the new initiation codon predicted by the software with green fluorescent protein followed by fluorescence microscopy and Western blotting showed that the first ATG downstream from the original initiation codon became the new translational initiation codon. The three-dimensional structure of the mutated protein predicted by alphafold2 revealed that it consisted of only six amino acids and failed to form a functional polypeptide or protein. Overexpression of the mutated LAMP2 c.2T>C showed a loss of function of the protein, as assessed by the dual-fluorescence autophagy indicator system. The mutation was confirmed to be null, AR experiments and sequencing results confirmed that 28% of the mutant X chromosome remained active. CONCLUSION: We propose possible mechanisms of mutations associated with haploinsufficiency of LAMP2: (1) The inactivation X chromosome carrying the mutation was not significantly skewed. However, it decreased in the mRNA level and the expression ratio of the mutant transcripts; (2) The identified mutation is null, and the active mutant transcript fails to translate into the normal LAMP2 proteins. The presence of haploinsufficiency in LAMP2 and the X chromosome inactivation pattern were crucial factors contributing to the early onset of Danon disease in this female patient.

Fecal Microbiota Transplantation Revealed a Pain-related Gut Microbiota Community in Ovariectomized Mice.

Higher sensitivity to pain is a common clinical symptom in postmenopausal females. The gut microbiota (GM) has recently been identified as participating in various pathophysiological processes and may change during menopause and contribute to multiple postmenopausal symptoms. Here, we investigated the possible correlation between GM alteration and allodynia in ovariectomized (OVX) mice. Results showed that OVX mice exhibited allodynia from 7 weeks after surgery compared with sham-operated (SHAM) mice by comparing pain-related behaviors. Fecal microbiota transplantation (FMT) from OVX mice induced allodynia in normal mice while FMT from SHAM mice alleviated allodynia in OVX mice. Microbiome 16S rRNA sequencing and linear discriminant analysis revealed alteration of the GM after OVX. Furthermore, Spearman's correlation analysis showed associations between pain-related behaviors and genera, and further verification identified the possible pain-related genera complex. Our findings provide new insights into the underlying mechanisms of postmenopausal allodynia, and suggest pain-related microbiota community as a promising therapeutic target. PERSPECTIVE: This article provided the evidence of gut microbiota playing essential roles in postmenopausal allodynia. This work intended to offer a guidance for further mechanism investigation into gut-brain axis and probiotics screening for postmenopausal chronic pain.

Semi-Immobilized Molecular Electrocatalysts for High-Performance Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries constitute promising next-generation energy storage devices due to the ultrahigh theoretical energy density of 2600 Wh kg-1. However, the multiphase sulfur redox reactions with sophisticated homogeneous and heterogeneous electrochemical processes are sluggish in kinetics, thus requiring targeted and high-efficient electrocatalysts. Herein, a semi-immobilized molecular electrocatalyst is designed to tailor the characters of the sulfur redox reactions in working Li-S batteries. Specifically, porphyrin active sites are covalently grafted onto conductive and flexible polypyrrole linkers on graphene current collectors. The electrocatalyst with the semi-immobilized active sites exhibits homogeneous and heterogeneous functions simultaneously, performing enhanced redox kinetics and a regulated phase transition mode. The efficiency of the semi-immobilizing strategy is further verified in practical Li-S batteries that realize superior rate performances and long lifespan as well as a 343 Wh kg-1 high-energy-density Li-S pouch cell. This contribution not only proposes an efficient semi-immobilizing electrocatalyst design strategy to promote the Li-S battery performances but also inspires electrocatalyst development facing analogous multiphase electrochemical energy processes.

Thoracoscopic and laparoscopic resection of a huge oesophageal liposarcoma: a case report.

Oesophageal liposarcomas are particularly rare, accounting for 1.2-1.5% of all gastrointestinal liposarcomas. Surgical resection is the usual treatment. Endoscopic resection is minimally invasive but still controversial. This current case report describes a rare case of a large oesophageal liposarcoma in a 52-year-old male that presented with 10-year history of dysphagia for dry and solid food that was exacerbated by a recent common cold. Thoracoscopic and laparoscopic oesophagectomy was performed. He did not have any dysphagia or dyspnoea 1 week postoperatively. The excised specimen consisted of a polypoid mass measuring 21.0 cm × 5.1 cm. Histological examination confirmed that it was an oesophageal liposarcoma. At 1-year postoperatively, there was no sign of recurrence. Thoracoscopy and laparoscopy can be used to treat large oesophageal masses. Long-term follow-up is required as oesophageal liposarcomas tend to recur.

MicroRNA-182 improves spinal cord injury in mice by modulating apoptosis and the inflammatory response via IKKß/NF-κB.

Spinal cord injury (SCI) is one common neurological condition which involves primary injury and secondary injury. Neuron inflammation and apoptosis after SCI is the most important pathological process of this disease. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. First, by re-analysis of Gene Expression Omnibus dataset (accession GSE19890), miR-182 was selected for further study because of its suppressive effects on the inflammatory response in the various types of injuries. Functional experiments demonstrated that miR-182 overexpression promoted functional recovery, reduced histopathological changes, and alleviated spinal cord edema in mice. It was also observed that miR-182 overexpression reduced apoptosis and attenuated the inflammatory response in spinal cord tissue, as evidenced by the reduction of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß, and the induction of IL-10. Using a lipopolysaccharide (LPS)-induced SCI model in BV-2 cells, we found that miR-182 was downregulated in the BV-2 cells following LPS stimulation, and upregulation of miR-182 improved LPS-induced cell damage, as reflected by the inhibition of apoptosis and the inflammatory response. IκB kinase ß (IKKß), an upstream target of the NF-κB pathway, was directly targeted by miR-182 and miR-182 suppressed its translation. Further experiments revealed that overexpression of IKKß reversed the anti-apoptosis and anti-inflammatory effects of miR-182 in LPS stimulated BV-2 cells. Finally, we found that miR-182 overexpression blocked the activation of the NF-κB signaling pathway in vitro and in vivo, as demonstrated by the downregulation of phosphorylated (p­) IκB-α and nuclear p-p65. Taken together, these data indicate that miR-182 improved SCI-induced secondary injury through inhibiting apoptosis and the inflammatory response by blocking the IKKß/NF-κB pathway. Our findings suggest that upregulation of miR-182 may be a novel therapeutic target for SCI.

Invasive thymoma extending into the superior vena cava and right atrium: The value of multimodal cardiac magnetic resonance.

The purpose of this case report is to describe the multimodal cardiac magnetic resonance (CMR) imaging features of an invasive thymoma extending into the superior vena cava and right atrium. This unusual case indicates that multimodal CMR can not only reveal the morphological features of thymoma but also enable the identification of histological types, which provides a reasonable surgical plan in the perioperative management. .

Integrated Bioinformatics Analysis of Hub Genes and Pathways Associated with a Compression Model of Spinal Cord Injury in Rats.

BACKGROUND Spinal cord injury (SCI) is a serious nervous system condition that can cause lifelong disability. The aim of this study was to identify potential molecular mechanisms and therapeutic targets for SCI. MATERIAL AND METHODS We constructed a weighted gene coexpression network and predicted which hub genes are involved in SCI. A compression model of SCI was established in 45 Sprague-Dawley rats, which were divided into 5 groups (n=9 per group): a sham operation group, and 1, 3, 5, and 7 days post-SCI groups. The spinal cord tissue on the injured site was harvested on 1, 3, 5, and 7 days after SCI and 3 days after surgery in the sham operation group. High-throughput sequencing was applied to investigate the expression profile of the mRNA in all samples. Differentially expressed genes were screened and included in weighted gene coexpression network analysis (WGCNA). Co-expressed modules and hub genes were identified by WGCNA. The biological functions of each module were investigated using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. RESULTS According to the RNA-seq data, a total of 1965 differentially expressed genes were screened, and WGCNA identified 10 coexpression modules and 5 hub genes. Module function analysis revealed that SCI was associated with immune response, cell division, neuron projection development, and collagen fibril organization. CONCLUSIONS Our study revealed dynamic changes in a variety of biological processes following SCI and identified 5 hub genes via WGCNA. These results provide insights into the molecular mechanisms and therapeutic targets of SCI.

A finite element analysis on comparing the stability of different posterior fixation methods for thoracic total en bloc spondylectomy.

OBJECTIVE: To compare the spinal stability with different fixation methods after thoracic TES using finite element analysis METHODS: The spinal finite element model was established from a healthy volunteer, and the validity was verified. The models of T8 thoracic total en bloc spondylectomy (TES) with and without artificial vertebral body were established combination with different fixation methods: the first was long segment fixation with fixed segments T5-7, T9-11; the second was short segment fixation with fixed segments T6-7, T9-10; the third was modified short segment with a pair of vertebral body screws on T7 and T9 added on the basis of short segment fixation. The motions of each model in standing state were simulated in software. The range of motion (ROM) and internal fixation stress changes were analyzed. RESULTS: When anterior support was effective, the three fixation methods could effectively maintain the stability of the spine. However, when anterior support failed, the ROM of the long segment fixation group and the short segment fixation group in the flexion-extension directions was significantly higher than that of when the anterior support existed, while the modified short segment fixation group had no significant changes. Meanwhile, the stress of internal fixation in the long segment fixation group and the short segment fixation group were greatly increased. However, there were no significant changes in modified short segment fixation group. CONCLUSION: After TES, the presence of the thoracic cage gives partial anterior stabilization. When the anterior support failed, the modified short segment fixation method can provide better stability.

Cage migration after unilateral instrumented transforaminal lumbar interbody fusion and associated risk factors: a modified measurement method.

OBJECTIVE: In this retrospective study, a modified measurement method was used to analyze cage migration during follow-up after unilateral instrumented transforaminal lumbar interbody fusion (TLIF) and identify associated factors. METHODS: We retrospectively evaluated 75 patients who had been treated with unilateral instrumented TLIF. Cage migration was quantitatively defined as anterior-posterior or lateral displacement of the cage. RESULTS: Five patients had significant cage migration (6.7%), but none developed severe neural symptoms during follow-up or underwent reoperation. The cages tended to migrate posteriorly or toward the side of surgery. The initial cage position and patient age were strongly associated with migration. Migration was less frequent when the cages were initially placed closer to the side of surgery. Patients of advanced age were more likely to develop anterior-posterior migration than were young patients. CONCLUSION: Cage migration is related to the initial position of the cage. Particular attention is required when performing unilateral instrumented TLIF in patients of advanced age because they are most likely to develop cage migration. Quantification of cage migration is an effective method of exploring the associated factors.

Predictors of long-term outcome after septal myectomy in symptomatic hypertrophic obstructive cardiomyopathy patients with previous alcohol septal ablation and residual obstruction.

BACKGROUND AND AIM: Recently alcohol septal ablation (ASA) has emerged as an alternative treatment for drug-refractory hypertrophic obstructive cardiomyopathy (HOCM) and a subgroup of HOCM patients with previous ASA may need myectomy. However, subsequent outcome and mechanism of residual obstruction has not been determined. This study aims to determine outcome after myectomy and mechanism of residual obstruction in HOCM patients with previous ASA. METHODS: From February 2009 to June 2017, 38 HOCM patients with previous ASA underwent surgical septal myectomy at our institution. Seventy-six patients who underwent surgical septal myectomy initially were included as the comparison group through one-to-two propensity score matching method. RESULTS: Fourteen available cardiac magnetic resonance images revealed inferior location and small area of infarcted myocardium induced by ASA in 12 patients and outside targeted location in two patients. During follow-up (median, 2.4; maximum, 7.8 years), event-free survival at 7 years was 83.2% in the previous ASA group and 94.6% in the comparison group, respectively (P = 0.0378). Multivariable analysis indicated previous ASA (hazard ratio, 4.28; 95% confidence intervals [CI], 1.20-15.26; P = 0.025) and postoperative left ventricular end-diastolic diameter (hazard ratio, 1.14; 95% CI, 1.05-1.23; P = 0.002) were independent predictors of adverse events. CONCLUSIONS: This study demonstrated that uncontrollable extent and location of infarcted myocardium induced by ASA may attribute to residual obstruction after previous ASA, and the long-term event-free survival after myectomy was inferior. It may provide special precaution to patient selection and the increased number of ASA practiced worldwide.

MiR-92b-3p promotes neurite growth and functional recovery via the PTEN/AKT pathway in acute spinal cord injury.

Emerging evidence indicates that microRNAs play an important role in neural remodeling, including neurite growth, after acute spinal cord injury (ASCI). This study aims to identify the mechanism by which miR-92b-3p regulates neurite growth in vivo and in vitro. Adult Sprague-Dawley rats were selected to establish the ASCI model, and the expressions of miR-92b-3p and phosphate and tensin homolog deleted on chromosome ten (PTEN) were quantified at different time points. The interaction between miR-92b-3p and PTEN was further detected in the PC12 cell line and dual-luciferase reporter assay. Neurite growth proteins (GAP43 and NF-200) were assessed by western blotting after miR-92b-3p mimics treatment. The PTEN/AKT pathway-related proteins and their roles in miR-92b-3p regulation were also identified using western blotting and immunofluorescence in vitro through LY294002, an AKT inhibitor. The effect of miR-92b-3p was further determined in vivo according to the Basso-Beattie-Bresnahan (BBB) Scale and GAP43 and NF-200 expressions. miR-92b-3p was downregulated after ASCI, while PTEN showed a simultaneous opposing trend. Overexpression of miR-92b-3p downregulated PTEN expression and promoted phosphorylation of AKT, as well as the expression of GAP43 and NF-200 in PC12 cells. Furthermore, the dual-luciferase reporter assay revealed that miR-92b-3p exerted its effect by targeting PTEN's 3'-untranslated regions and that this effect could be counteracted by AKT phosphorylation blocker LY294002 through western blotting and immunofluorescence. Moreover, miR-92b-3p could also improve the BBB scale as well as GAP43 and NF-200 expression levels in vivo. Collectively, these results indicate that miR-92b-3p promotes neurite growth and functional recovery through the PTEN/AKT pathway in ASCI.

The need for bone biopsies in the diagnosis of new bone lesions in patients with a known primary malignancy: A comparative review of 117 biopsy cases.

OBJECTIVE: This study used a clinical dataset to investigate the proportion of the newly found bone lesions in malignant patients diagnosed by biopsy as being benign, malignant but unrelated to the primary malignancy, or bone metastases of the primary malignancy. The clinical factors that might affect the correlation between bone lesions and the primary malignancy were also analyzed. It is expected to obtain some information contributing to the clinical decision-making regarding the need for biopsy of these lesions from the research results. METHODS: Data from patients with a single known malignant tumor who had undergone biopsy of newly found bone lesions at our research institution between January 2012 and December 2017 were reviewed. Based on the pathology results, included cases were divided into a bone-metastasis-of-primary-tumor group (Group 1) and a non-bone-metastasis-of-primary-tumor group (Group 2). The sex, age, diagnostic interval time between the primary malignancy and bone lesions, clinical symptoms, number of involved bones, sites of bone biopsy, and 18F-FDG PET/CT results were compared between groups. RESULTS: A total of 117 patients (92 in Group 1 and 25 in Group 2) were included in the study. There was no significant difference in the sex, age or diagnostic interval time between patient groups. Of all the cases, 17.9% (21/117) were identified to be benign lesions such as fibrous dysplasia (n = 2), bone tuberculosis (n = 1), simple bone cyst (n = 1), aneurysmal bone cyst (n = 1), or solitary fibrous tumor (n = 1). Meanwhile, 3.4% (4/117) were new malignancies including chondrosarcoma (n = 1), plasmacytoma (n = 1) and bone metastases unrelated to the primary malignancy (n = 2). Bone metastases pertinent to the primary tumor accounted for 78.6% (92/117) of cases. Liver (n = 18), kidney (n = 14), breast (n = 13) and lung (n = 12) were the most common cancers among cases. Cases with clinical symptoms exhibited a higher likelihood of their bone lesions being diagnosed as bone metastases of their primary malignancy than those without clinical symptoms (81.3% (87/107) vs. 50.0% (5/10)) (P = 0.021). Neither the number of bone lesions nor the biopsy sites appeared to influence whether the bone lesions were metastases of the primary malignancy or not. In PET/CT examination, the mean maximum standardized uptake values of the two groups were similar. CONCLUSIONS: This study indicated that more than 1/5 of newly identified bone lesions in patients with a single known malignancy were not clinically associated with their primary tumors. Furthermore, 3.4% of these were newly discovered malignant bone tumors. The presence of clinical symptoms may be a significant factor affecting whether a new bone lesion is clinically linked to a patient's primary malignancy. Based on the experience from these patients, as for the newly found bone lesions, it is worthy to perform an active biopsy on those asymptomatic ones to avoid misdiagnosis and less biopsy on symptomatic ones for the sake of less cost and risks.