Laser navigation combined with XperCT technology-assisted puncture of basal ganglia intracerebral hemorrhage.

Basal ganglia hemorrhage, which is characterized by excessive incapacity charge and high mortality rates, is surgically treated by minimally invasive hematoma puncture and drainage. We aimed at determining the efficacy of laser-guided minimally invasive hematoma puncture and drainage for treatment of basal ganglia hemorrhage. A total of 61 patients with hypertensive basal ganglia hemorrhage were recruited at the Binzhou Medical University Hospital, between October 2019 and January 2021, and their clinical information retrospectively analyzed. Based on the surgical approach used, patients were assigned into either laser navigation or small bone window groups depending on the surgical approach. Then, we compared the operation times, intraoperative blood loss, clinic stay, Glasgow Outcome Score (GOS) rating at 30 days, Barthel index (BI) rating at 6 months, postoperative pneumonia incidences, and intracranial contamination complications between groups. Intraoperative blood loss, operation time, and sanatorium were significantly low in laser navigation group, relative to the small bone window group. At the same time, there were no significant differences between the groups with regard to postoperative hematoma volume, lung contamination, cerebrospinal fluid (CSF) leak, and intracranial contamination, as well as the 6-month BI and 30-day GOS rating. There were no deaths in either group. Compared with the traditional small bone window surgery, laser-guided puncture and drainage is a low-cost, accurate, and safe method for the treatment of basal ganglia hemorrhage, which is suitable for promotion in developing countries and economically underdeveloped areas.

Transcatheter closure of perimembranous ventricular septal defect using a novel fully bioabsorbable occluder: multicenter randomized controlled trial.

Although the use of bioabsorbable occluder is expected to reduce the risk of metal occluder-related complications, it has not been approved due to incomplete degradation and new complications. Novel fully bioabsorbable occluders were designed to overcome such limitations. The aim of this study was to investigate the efficacy and safety of a fully biodegradable occluder in patients with ventricular septal defects. 125 patients with perimembranous ventricular septal defect (VSD) larger than 3 mm were screened from April 2019 to January 2020 in seven centers. 108 patients were enrolled and randomized into the bioabsorbable occluder group (n = 54 patients) and nitinol occluder group (n = 54). A non-inferiority design was utilized and all patients underwent transcatheter device occlusion. Outcomes were analyzed with a 24-month follow-up. All patients were successfully implanted and completed the trial. No residual shunt >2 mm was observed during follow-up. Transthoracic echocardiography showed a hyperechoic area corresponding to the bioabsorbable occluder which decreased primarily during the first year after implantation and disappeared within 24 months. Postprocedural arrhythmia was the only occluder-related complication with an incidence of 5.56% and 14.81% for the bioabsorbable and nitinol groups, respectively (P = 0.112). The incidence of sustained conduction block was lower in the bioabsorbable occluder group (0/54 vs. 6/54, P = 0.036) at 24-month follow-up. In conclusion, the novel fully bioabsorbable occluder can be successfully and safely implanted under echocardiography guidance and reduce the incidence of sustained postprocedural arrythmia. The efficacy and safety of this fully biodegradable occluder are non-inferior to that of a traditional nitinol one.

Hypertensive intracerebral hemorrhage: Which one should we choose between laser navigation and 3D navigation mold?

Background: Hypertensive intracerebral hemorrhage (HICH) is a severe life-threatening disease, and its incidence has gradually increased in recent years. Due to the particularity and diversity of its bleeding sites, the early treatment of hematoma needs to be more meticulous and accurate, and minimally invasive surgery is often one of the measures that are commonly adopted now. The lower hematoma debridement and the navigation template created by 3D printing technology were compared in the external drainage of a hypertensive cerebral hemorrhage. Then the effect and feasibility of the two operations were explicitly evaluated. Material and methods: We performed a retrospective analysis of all eligible patients with HICH who underwent laser-guided hematoma evacuation or hematoma puncture under 3D-navigated molds at the Affiliated Hospital of Binzhou Medical University from January 2019 to January 2021. A total of 43 patients were treated. Twenty-three patients were treated with laser navigation-guided hematoma evacuation (group A); 20 patients were treated with 3D navigation minimally invasive surgery (group B). A comparative study was conducted between the two groups to evaluate the preoperative and postoperative conditions. Results: The preoperative preparation time of the laser navigation group was significantly shorter than that of the 3D printing group. The operation time of the 3D printing group was better than that of the laser navigation group (0.73 ± 0.26 h vs. 1.03 ± 0.27 h P = 0.00070). In the improvement in the short-term postoperatively, there was no statistically significant difference between the laser navigation group and the 3D printing group (Median hematoma evacuation rate P = 0.14); And in the three-month follow-up NIHESS score, there was no significant difference between the two (P = 0.82). Conclusion: Laser-guided hematoma removal is more suitable for emergency operations, with real-time navigation and shortened preoperative preparation time; hematoma puncture under a 3D navigation mold is more personalized and shortens the intraoperative time course. There was no significant difference in therapeutic effect between the two groups.

Identification of Chromatin Regulatory Factors Related to Immunity and Treatment of Alzheimer's Disease.

Alzheimer's disease is one of the common neurodegenerative diseases in the elderly, which mainly manifests as progressively severe cognitive impairment, which seriously affects the quality of life of patients. Chromatin regulators have been shown to be associated with a variety of biological processes, and we mainly explore the relationship between chromatin regulators and Alzheimer's disease. Eight hundred seventy chromatin regulators were collected from previous studies, and data related to Alzheimer's disease patients were downloaded from the GEO database. Finally, we screened chromatin regulators related to Alzheimer's disease immunity, established prediction models, and screened related drugs and miRNAs. We screened 160 differentially expressed CRs, constructed an interaction network, obtained 10 hub genes, successfully constructed a prediction model based on immune-related 5 CRs, and obtained 520 related drugs and 3 related miRNA, which provided an idea for the treatment of Alzheimer's disease. Our study identified 5 chromatin regulators related to Alzheimer's disease, which are expected to be new targets for Alzheimer's disease immunotherapy.

An enriched environment improves long-term functional outcomes in mice after intracerebral hemorrhage by mechanisms that involve the Nrf2/BDNF/glutaminase pathway.

Post-stroke depression exacerbates neurologic deficits and quality of life. Depression after ischemic stroke is known to some extent. However, depression after intracerebral hemorrhage (ICH) is relatively unknown. Increasing evidence shows that exposure to an enriched environment (EE) after cerebral ischemia/reperfusion injury has neuroprotective effects in animal models, but its impact after ICH is unknown. In this study, we investigated the effect of EE on long-term functional outcomes in mice subjected to collagenase-induced striatal ICH. Mice were subjected to ICH with the standard environment (SE) or ICH with EE for 6 h/day (8:00 am-2:00 pm). Depressive, anxiety-like behaviors and cognitive tests were evaluated on day 28 with the sucrose preference test, tail suspension test, forced swim test, light-dark transition experiment, morris water maze, and novel object recognition test. Exposure to EE improved neurologic function, attenuated depressive and anxiety-like behaviors, and promoted spatial learning and memory. These changes were associated with increased expression of transcription factor Nrf2 and brain-derived neurotrophic factor (BDNF) and inhibited glutaminase activity in the perihematomal tissue. However, EE did not change the above behavioral outcomes in Nrf2-/- mice on day 28. Furthermore, exposure to EE did not increase BDNF expression compared to exposure to SE in Nrf2-/- mice on day 28 after ICH. These findings indicate that EE improves long-term outcomes in sensorimotor, emotional, and cognitive behavior after ICH and that the underlying mechanism involves the Nrf2/BDNF/glutaminase pathway.

A fully biodegradable polydioxanone occluder for ventricle septal defect closure.

Ventricular septal defect (VSD) is one of the commonest congenital heart diseases (CHDs). Current occluders for VSD treatment are mainly made of nitinol, which has the risk of nickel allergy, persistent myocardial abrasion and fatal arrythmia. Herein, a fully biodegradable polydioxanone (PDO) occluder equipped with a shape line and poly-l-lactic acid PLLA membranes is developed for VSD closure without the addition of metal marker. PDO occluder showed great mechanical strength, fatigue resistance, geometry fitness, biocompatibility and degradability. In a rat subcutaneous implantation model, PDO filaments significantly alleviated inflammation response, mitigated fibrosis and promoted endothelialization compared with nitinol. The safety and efficacy of PDO occluder were confirmed in a canine VSD model with 3-year follow-up, demonstrating the biodegradable PDO occluder could not only effectively repair VSD, induce cardiac remodeling but also address the complications associated with metal occluders. Furthermore, a pilot clinical trial with five VSD patients indicated that all the occluders were successfully implanted under the guidance of echocardiography and no adverse events occurred during the 3-month follow-up. Collectively, the fully bioresorbable PDO occluder is safe and effective for clinical VSD closure and holds great promise for the treatment of structural CHDs.

Bioinformatic analysis of potential biomarkers and mechanisms of immune infiltration in mitral regurgitation complicated by atrial fibrillation.

Background: Mitral regurgitation (MR) is one of the most prevalent valvular diseases. Degenerated MR-induced volume overload leads to left atrial enlargement and eventually, atrial fibrillation (AF). AF has a negative effect on patient prognosis despite recent advances in minimal invasive transcatheter devices for valve surgery. However, more effective strategies aimed at precisely treating from pathophysiology and genetic perspective are scarce. Methods: The gene expression datasets, GSE109744 and GSE79768, were obtained from the Gene Expression Omnibus database and analyzed to identify the differentially expressed genes (DEGs) in patients with mitral value prolapse (MVP) and AF. Subsequently, we predicted the extensive miRNA targets, and the protein-protein interaction (PPI) and miRNA-target gene regulatory networks were established. Functional enrichment analyses were performed for the DEGs. In addition, the co-expressed DEGs coupled with their predicted miRNAs and disease phenotypes involved in MVP and AF were assessed. Finally, the immune infiltration in both datasets was examined. Results: A total of 491 and 180 DEGs were identified in the mitral valve and left atrial specimens, respectively. From these, 11 integrated co-expressed DEGs were identified, namely, PRG4, GPR34, RELN, CA3, IL1B, EPHA3, CHGB, TCEAL2, B3GALT2, ASB11, and CRISPLD1. The enriched Gene Ontology terms and KEGG pathways associated with the DEGs were determined, and the top 10 hub genes and top 3 gene clusters were selected from the PPI network. A prediction of target miRNAs was performed based on the co-expressed DEGs. The enrichment of the co-expressed DEGs suggested that immune and inflammatory responses might be involved in the disease development through multiple immune related pathways, including the interaction of cytokines and chemokines. Notably, this result was consistent with the immune infiltration analysis since the proportions of naïve B cells and memory B cells were significantly different in MVP and AF tissues compared to normal tissues. Conclusions: MR and AF are related, and 11 co-expressed DEGs were found to be significantly associated with MVP with AF, and indeed, these may represent novel biomarkers. Several immune cells were found to contribute to the process of MVP and AF via diverse mechanisms, in particular, antigen-presenting cells.

Perimedullary arteriovenous fistula was misdiagnosed as intervertebral disc herniation: A case report.

INTRODUCTION: Spinal perimedullary arteriovenous fistula (PMAVFS) is a rare intradural vascular malformation with a high rate of misdiagnosis. In adults, most spinal PMAVFs are small and low-flow, starting with progressive spinal dysfunction. PATIENT CONCERNS: The patient was a 58-year-old male who presented with both lower limbs numb with intermittent walking weakness, obvious at both ankles, and no obvious inducing and relieving factors. The local hospital considered the diagnosis of lumbar disc herniation after MR examination; he was treated with lumbar fixation and fusion. DIAGNOSIS: After admission, a ce-MRA examination showed that the left spinal artery at the T10 level showed small branch blood vessels in the local area. The distal end was unclear, which seemed to be connected with the drainage vein of the spinal cord. The digital subtraction angiography (DSA) result indicated that the left intercostal artery of T10 sent the Adamkiewicz artery down to the level of L4, and an arteriovenous fistula was seen. The fistula was located at the lower edge of the L4 level and then drained to the upper premedullary vein to the level of T4 after a short descending. It was finally diagnosed as a perimedullary arteriovenous fistula. INTERVENTIONS: It was cured by cutting the arteriovenous fistula in the spinal canal by indocyanine green-assisted angiography. OUTCOMES: we report a case of PMAVFS misdiagnosed as lumbar disc herniation with resection and internal fixation. In our hospital, the final diagnosis was a perimedullary arteriovenous fistula, which was cured by cutting off the arteriovenous fistula within the spinal canthus. CONCLUSION: Spinal perimedullary arteriovenous fistula (PMAVFS) is a rare intradural vascular malformation with a high rate of misdiagnosis. In adults, most spinal PMAVFs are small and low-flow, starting with progressive spinal dysfunction. It is hoped that this can provide warnings to more neurosurgeons and reduce the occurrence of misdiagnosis.

Neuroblastoma Suppressor of Tumorigenicity 1 Mediates Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension Related to Congenital Heart Disease.

Endothelial-to-mesenchymal transition (EndMT) plays a critical role in the flow-induced vascular remodeling process, such as pulmonary arterial hypertension (PAH) related to congenital heart disease (CHD). NBL1 (neuroblastoma suppressor of tumorigenicity 1) is a secreted glycoprotein that has been implicated in CHD-PAH by aggravating the phenotypic transformation of smooth muscle cells. However, the underlying mechanisms regarding the interplay between NBL1 and endothelial cells in CHD-PAH remain to be fully elucidated. Thus, we aimed to identify the potential effect of NBL1 on EndMT using a novel flow-associated PAH model with Nbl1 knockout rats. The phenotype of EndMT was detected using RNA sequencing and further examined using western blotting and immunostaining of pulmonary arteries. Our observations demonstrated that the novel strategy of Nbl1 knockout effectively attenuated flow-associated PAH through downregulation of EndMT to some extent. Mechanistic experiments were established on human pulmonary artery endothelial cells to confirm that EndMT was induced by NBL1 in vitro. After 7 days' stimulation with NBL1, concentrations of EndMT-related biomarkers and downstream transcription factors were quantified using RNA sequencing, western blotting, and immunocytochemistry. Both in vitro and in vivo experiments supported the imbalance of increased TGF-ß (transforming growth factor-ß) and dysregulation of BMP (bone morphogenetic protein) signaling by NBL1. Blocking the canonical TGF-ß pathway efficiently preserved endothelial function upon NBL1 stimulation. These data suggested that NBL1 aggravated flow-associated PAH by inducing EndMT via the TGF-ß and BMP signaling pathway. Thus, antagonizing NBL1 and rebalancing TGF-ß and BMP signaling may be a suitable therapeutic target for CHD-PAH.

Xper-CT combined with laser-assisted navigation radiofrequency thermocoagulation in the treatment of trigeminal neuralgia.

Objective: Our objective was to study the clinical feasibility of Xper-CT combined with laser-assisted radiofrequency thermocoagulation in the treatment of trigeminal neuralgia. Materials and methods: A retrospective analysis was made of 60 patients with trigeminal neuralgia who visited the Affiliated Hospital of Binzhou Medical University from January 2019 to May 2021. According to the different surgical methods, we were divided into C-arm X-ray group and laser navigation group. The operation time, operative complications, post-operative 24 h, post-operative 3 and 6 months Barrow Neurotics Institute (BNI) score were recorded and compared. Results: Compared with the C-arm X-ray-guided puncture group, Xper-CT combined with laser-assisted navigation has the obvious advantages of shorter total puncture time, shorter surgical time, higher success rate of first puncture, and better surgical effect. Conclusion: Radiofrequency therapy of trigeminal neuralgia with Xper-CT combined with laser-assisted navigation has a good clinical effect and can be promoted and applied.

OsHXK3 encodes a hexokinase-like protein that positively regulates grain size in rice.

KEY MESSAGE: We report the map-based cloning and functional characterization of SNG1, which encodes OsHXK3, a hexokinase-like protein that plays a pivotal role in controlling grain size in rice. Grain size is an important agronomic trait determining grain yield and appearance quality in rice. Here, we report the discovery of rice mutant short and narrow grain1 (sng1) with reduced grain length, width and weight. Map-based cloning revealed that the mutant phenotype was caused by loss of function of gene OsHXK3 that encodes a hexokinase-like (HKL) protein. OsHXK3 was associated with the mitochondria and was ubiquitously distributed in various organs, predominately in younger organs. Analysis of glucose (Glc) phosphorylation activities in young panicles and protoplasts showed that OsHXK3 was a non-catalytic hexokinase (HXK). Overexpression of OsHXK3 could not complement the Arabidopsis glucose insensitive2-1 (gin2-1) mutant, indicating that OsHXK3 lacked Glc signaling activity. Scanning electron microscopy analysis revealed that OsHXK3 affects grain size by promoting spikelet husk cell expansion. Knockout of other nine OsHXK genes except OsHXK3 individually did not change grain size, indicating that functions of OsHXKs have differentiated in rice. OsHXK3 influences gibberellin (GA) biosynthesis and homeostasis. Compared with wild type, OsGA3ox2 was significantly up-regulated and OsGA2ox1 was significantly down-regulated in young panicle of sng1, and concentrations of biologically active GAs were significantly decreased in young panicles of the mutants. The yield per plant of OsHXK3 overexpression lines (OE-4 and OE-35) was increased by 10.91% and 7.62%, respectively, compared to that of wild type. Our results provide evidence that an HXK lacking catalytic and sensory functions plays an important role in grain size and has the potential to increase yield in rice.

Laser Navigation Combined With XperCT Technology Assisted Puncture of Brainstem Hemorrhage.

Background: Brainstem hemorrhage has a rapid onset with high mortality and disability rates. In recent years, an increasing number of studies have reported on the surgical treatment of brainstem hemorrhage. The introduction of stereotaxic instruments and navigation systems has improved the accuracy of surgical treatment; however, the popularity of these devices in the primary hospitals is not high. In this study, we introduce laser navigation combined with the XperCT technology to assist in the puncture and drainage of brainstem hemorrhage, aiming to improve surgical accuracy and facilitate the drainage of brainstem hemorrhage in primary hospitals. Material and Methods: A total of five patients (four men and one woman), aged 34-70 years, who underwent hematoma puncture drainage with the assistance of laser navigation combined with XperCT technology at the Binzhou Medical University Hospital, China, between June 2020 and Aug 2021 were included in the study. The brainstem hemorrhages had volumes of 7-18 ml. Statistical analyses of the postoperative puncture deviation distance (distance between the actual puncture end and simulated puncture end) and postoperative improvement were also performed. Results: The operations were successfully completed in all five patients. The puncture deviation distance was <6 mm in all five patients and <2 mm in two patients. The postoperative hematoma clearance rate was about 70%-90%. Among four patients with respiratory failure, three had improved breathing and resumed spontaneous breathing. Out of three patients with high fever, one showed a substantial decrease in body temperature. There were no cases of postoperative infection. Of the five patients, two recovered consciousness, one died, and two voluntarily gave up further treatment and were discharged. Conclusions: Laser navigation combined with the XperCT technology could improve the accuracy of surgical puncture. The technique might be convenient for widespread clinical application because of its low trauma, high precision, short operation time, and low operation cost.

Systematic analysis of critical genes and pathways identified a signature of neuropathic pain after spinal cord injury.

Spinal cord injury (SCI) damages sensory systems, producing chronic neuropathic pain that is resistant to medical treatment. The specific mechanisms underlying SCI-induced neuropathic pain (SCI-NP) remain unclear, and protein biomarkers have not yet been integrated into diagnostic screening. To better understand the host molecular pathways involved in SCI-NP, we used the bioinformatics method, the PubMed database and bioinformatics methods to identify target genes and their associated pathways. We reviewed 2504 articles on the regulation of SCI-NP and used the text mining of PubMed database abstracts to determine associations among 12 pathways and networks. Based on this method, we identified two central genes in SCI-NP: interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). Adult male Sprague-Dawley rats were used to build the SCI-NP models. The threshold for paw withdrawal was significantly reduced in the SCI group, and TLR4 was activated in microglia after SCI. Enzyme-linked immunosorbent assay（ELISA) analysis of TNF-α and IL-6 levels was significantly higher in the SCI group than in the sham group. Western blot showed that expressions of the TLR4/MyD88/NF-κB inflammatory pathway protein increased dramatically in the SCI group. Using the TLR4 inhibitor TAK-242, the pain threshold and expressions of inflammatory factors and proteins of the proteins of the inflammatory signal pathway were reversed, TLR4 in microglia was suppressed, suggesting that SCI-NP was related to neuroinflammation mediated by the TLR4 signalling pathway. In conclusion, we found that TNF-α and IL-6 were the neuroinflammation-related genes involved in SCI-NP that can be alleviated by inhibiting the inflammatory pathway upstream of the TLR4/MyD88/NF-κB inflammatory pathway.