Identification of PANoptosis-related predictors for prognosis and tumor microenvironment by multiomics analysis in glioma.

PANoptosis is a newly described inflammatory programmed cell death, that highlights coordination between pyroptosis, apoptosis and necroptosis. However, the functions of PANoptosis-related genes in glioma progression still remain to be explored. This study aims to identify PANoptosis-related predictors that may be utilized for prognosis prediction and development of new therapeutic targets. Firstly, bulk and single-cell RNA-seq (scRNA-seq) data of glioma patients were extracted from TCGA, CGGA and GEO database. Genetic analysis indicates a considerably high mutation frequency of PANoptosis-related genes (PANRGs) in glioma. Consensus clustering was applied to reveal different subtypes of glioma based on PANRGs. Two PANoptosis subtypes with distinct prognostic and TME characteristics were identified. Then, with LASSO-Cox regression analysis, four PANoptosis-related predictors (MYBL2, TUBA1C, C21orf62 and KCNIP2) were determined from bulk and scRNA-seq analysis. Predictive PANRG score model was established with these predictors and its correlation with tumor microenvironment (TME) was investigated. The results showed that patients with low PANRG score, had higher infiltration of anti-tumor immune cells, higher MSI score and lower TIDE score, which are more likely to benefit from immunotherapy. Further analysis identified 16 potential drugs associated with PANoptosis-related predictors. Moreover, the expression levels of four PANoptosis-related predictors were examined in clinical samples and the results were consistent with those analyzed in the database. Besides, we also confirmed the biological functions of two oncogenic predictors (MYBL2 and TUBA1C) by cell experiments, which revealed that knockdown of MYBL2 or TUBA1C could significantly inhibit the proliferation and migration of glioma cells. These findings highlight the prognostic value and biological functions of PANRGs in glioma, which may provide valuable insights for individualized treatment.

EMNPD: a comprehensive endophytic microorganism natural products database for prompt the discovery of new bioactive substances.

The discovery and utilization of natural products derived from endophytic microorganisms have garnered significant attention in pharmaceutical research. While remarkable progress has been made in this field each year, the absence of dedicated open-access databases for endophytic microorganism natural products research is evident. To address the increasing demand for mining and sharing of data resources related to endophytic microorganism natural products, this study introduces EMNPD, a comprehensive endophytic microorganism natural products database comprising manually curated data. Currently, EMNPD offers 6632 natural products from 1017 endophytic microorganisms, targeting 1286 entities (including 94 proteins, 282 cell lines, and 910 species) with 91 diverse bioactivities. It encompasses the physico-chemical properties of natural products, ADMET information, quantitative activity data with their potency, natural products contents with diverse fermentation conditions, systematic taxonomy, and links to various well-established databases. EMNPD aims to function as an open-access knowledge repository for the study of endophytic microorganisms and their natural products, thereby facilitating drug discovery research and exploration of bioactive substances. The database can be accessed at http://emnpd.idrblab.cn/ without the need for registration, enabling researchers to freely download the data. EMNPD is expected to become a valuable resource in the field of endophytic microorganism natural products and contribute to future drug development endeavors.

Hypoxia Affects Autophagy in Human Umbilical Vein Endothelial Cells via the IRE1 Unfolded Protein Response.

OBJECTIVE: The purpose of this study was to investigate the role of the unfolded protein response, specifically the inositol-requiring enzyme 1 (IRE1) signaling pathway, in hypoxia-induced autophagy in human umbilical venous endothelial cells (HUVECs). METHODS: The expression of IRE1 and autophagy relative protein in HUVECs with hypoxia was explored by Western blotting, qRT-PCR and confocal microscopy. Further, we evaluated the biological effects of HUVECs by tube formation assay and wound healing assay in vitro. Finally, we examined the function of IRE1 in local blood vessels through animal models. RESULTS: Hypoxia activated the IRE1 signaling pathway and induced autophagy in a time-dependent manner in HUVECs and further influenced the biological effects of HUVECs. Intraperitoneal injection of IRE1 inhibitors inhibited local vascular autophagy levels and lipid accumulation in model animals. CONCLUSION: Hypoxia can induce autophagy and activate the IRE1 signaling pathway in HUVECs and the IRE1 signaling pathway is involved in autophagy in hypoxic conditions.

Identification of line-source transfer mobility and force density by ground acceleration measurements.

Ground-borne vibration caused by railway traffic has been a research concern due to its possible side effects on nearby residences. The force density and line-source mobility can effectively characterize the generation and transmission of train-induced vibrations, respectively. This research proposed a frequency-domain method for identifying the line-source transfer mobility and force density using measured vibrations at the ground surface, which was on the basis of the least-square method. The proposed method was applied to a case study at Shenzhen Metro in China, where a total of seven fixed-point hammer impacts with 3.3 m equal intervals were used to represent the train vibration excitations. Line-source transfer mobility of the site and force density levels of the metro train were identified, respectively. Causes for different dominant frequencies can be traced by separating the dynamic characteristics of vibration excitation and transmission. It was found in the case study that at a location 3 m away from the track, the peak at 50 Hz was caused by excitations, while that at 63 Hz was attributed to transmission efficiency related to the soil properties. Subsequently, numerical validations of the fixed-point loads' assumption and identified force density levels were carried out. Good comparisons between numerically predicted and experimentally identified force density levels indicated the feasibility of the proposed method. At last, the identified line-source transfer mobility and force density levels were applied to the forward problem, i.e., making predictions of train-induced vibrations. The predicted ground and structural vibrations at different locations were compared to corresponding measurements, with good agreement, which experimentally validated the identification method. The identification results of the case study can be employed by similar railway systems as a good reference.

Intravenous Thrombolysis for Acute Ischemic Stroke in Patients With Cardiac Myxoma: A Case Series and Pooled Analysis.

Background and Purpose: Acute ischemic stroke (AIS) is a major life-threatening consequence of cardiac myxoma (CM) and leads to a poor prognosis. Although intravenous thrombolysis (IVT) is the first-line treatment for AIS, its efficacy and safety in CM-AIS have not been established. Currently, there are only limited data from case reports. Our study aimed to investigate the clinical characteristics of CM-AIS and evaluate the safety and efficacy of IVT for CM-AIS patients. Methods: Fourteen CM-AIS patients who received IVT between January 2016 and December 2021 were identified from our multicenter stroke registry databases. Clinical, neuroimaging and outcome data were analyzed. We then performed a pooled analysis of the published literature from inception to December 2021. Results: Of the 14 CM-AIS patients, nine were treated with IVT alone, and five were treated with bridging therapy (BT). The median age was 51.5 years, and 57.1% were female. The median onset-to-needle time was 160 min. The median National Institute of Health Stroke Score (NIHSS) decreased from 15.5 at presentation to 13 24 h after IVT. Very early neurological improvement (VENI) was observed in one patient. Hemorrhagic transformation (HT) was observed in five (35.7%) patients, and only one patient was symptomatic (7.1%). Three-month favorable outcomes were achieved in six patients (66.7%) who underwent IVT alone and three patients (60%) who received BT, which resulted in a total proportion of favorable outcomes of 64.3%. None of the patients died at 3 months follow-up. Forty-seven cases (15 BT patients) were included for the pooled analysis. The median NIHSS score was 16.5, and VENI was observed in 10 (21.3%) patients. HT was detected in 11 patients (23.4%), and four (8.5%) patients were symptomatic. Favorable outcomes at 3 months were achieved in 61.7% of patients, 56.3% of patients who underwent IVT alone, and 73.3% of patients who received BT. The 3-month mortality rate was 4.3%. Conclusions: IVT is a potentially safe and efficient treatment for CM-AIS patients. Further studies with larger sample sizes are required to provide more evidence on the safety and efficacy of IVT and BT in CM-AIS patients.

Mesenchymal Stromal Cell Therapy in Spinal Cord Injury: Mechanisms and Prospects.

Spinal cord injury (SCI) often leads to severe motor, sensory, and autonomic dysfunction in patients and imposes a huge economic cost to individuals and society. Due to its complicated pathophysiological mechanism, there is not yet an optimal treatment available for SCI. Mesenchymal stromal cells (MSCs) are promising candidate transplant cells for use in SCI treatment. The multipotency of MSCs, as well as their rich trophic and immunomodulatory abilities through paracrine signaling, are expected to play an important role in neural repair. At the same time, the simplicity of MSCs isolation and culture and the bypassing of ethical barriers to stem cell transplantation make them more attractive. However, the MSCs concept has evolved in a specific research context to encompass different populations of cells with a variety of biological characteristics, and failure to understand this can undermine the quality of research in the field. Here, we review the development of the concept of MSCs in order to clarify misconceptions and discuss the controversy in MSCs neural differentiation. We also summarize a potential role of MSCs in SCI treatment, including their migration and trophic and immunomodulatory effects, and their ability to relieve neuropathic pain, and we also highlight directions for future research.

Malignant Isolated Cortical Vein Thrombosis as the Initial Manifestation of Primary Antiphospholipid Syndrome: Lessons on Diagnosis and Management From a Case Report.

Background: Antiphospholipid syndrome (APS) with isolated cortical vein thrombosis (ICoVT) is an extremely rare but potentially malignant entity. It is particularly challenging to diagnose APS-related ICoVT because of the non-specific clinical manifestations and the frequent absence of typical neuroimaging. Moreover, there is currently limited knowledge on the clinical features and management strategies for the condition. Delays in diagnosis and treatment may lead to life-threatening consequences. Case Presentation: We present a rare case of a 74-year-old Chinese woman who presented with sudden onset of headache and right arm weakness that mimicked acute ischemic stroke. Her initial computed tomography was unremarkable, and intravenous thrombolysis was performed. Serial neuroimages confirmed ICoVT 4 days after symptom onset, and low-molecular-weight heparin (LMWH) was started at a dose of 0.4 ml twice per day, according to the 2019 Chinese guidelines. The workup for the predisposing causes of ICoVT revealed triple positivity APS. LMWH dose was adjusted according to the anti-Xa chromogenic assay. However, the patient's condition deteriorated rapidly, and there was a progressive enlargement of the venous infarction despite treatment with anticoagulants. Transtentorial herniation developed on day 12, and decompressive craniectomy was immediately performed. The patient's symptoms did not improve significantly after surgery, and she remained aphasic and hemiplegic at the 3-month follow-up, with a modified Rankin Scale score of 5. Conclusion: ICoVT is a rare yet potentially fatal manifestation of APS, and its diagnosis and treatment are extremely challenging. Timely diagnosis, prompt treatment, and close monitoring are essential to improve the clinical prognosis of patients with APS-related ICoVT.

Mechanical Thrombectomy for Acute Ischemic Stroke in Patients With Cardiac Myxoma: A Case Series and Pooled Analysis.

Background and Purpose: Acute ischemic stroke (AIS) is a common and life-threatening complication of patients with cardiac myxoma (CM). The role of the mechanical thrombectomy (MT) technique in CM-AIS patients remains unclear, and no guidelines exist for this population. Therefore, we conducted a case series study of MT in CM-AIS patients to investigate its safety and efficacy via a pooled analysis of published literature. Methods: Eleven CM-AIS patients who underwent MT between 2016 and 2021 were screened from multicenter stroke databases. Clinical, procedural, and outcome data were obtained from medical records. A systematic review was conducted to identify additional cases from published studies by searching PubMed and China National Knowledge Infrastructure databases. We then performed a pooled analysis of the published cases. Results: In the case series study, most patients were male (81.8%), with a median age of 51 years. All patients had CM located in the left atrium. The rate of successful reperfusion using the first-line thrombectomy technique was 100% with stent retriever (SR) and 66.7% with direct aspiration (DA), which resulted in overall successful reperfusion in 94.1% of all occlusions. The retrieved emboli of the five patients who underwent histopathology examination were identified as myxoma components. Hemorrhagic transformation was observed in five (45.5%) patients, of whom one was symptomatic (9.1%). Three-month favorable functional outcomes were achieved in five (45.5%) patients with a 3-month mortality rate of 18.2%. For the literature review, 35 cases with 51 target vessel occlusions were identified and included in the pooled analysis. The rate of successful reperfusion following first-line thrombectomy did not differ between SR (30 patients, 90.9%) and DA (10 patients, 83.3%). The overall successful reperfusion rate was 91.8% of all occlusions. Three-month favorable functional outcomes were achieved in 21 (60.0%) patients, and the mortality rate was 8.6%. Conclusions: Our findings suggest that MT is not only an effective technique but also a safe option for CM-AIS patients with large vessel occlusion. MT has several advantages for this population, which include a high recanalization rate, low bleeding risk, and the ability to evaluate the source of emboli and the etiology of stroke.

Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: A narrative review.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis (PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with supportive care, the median survival of HCC with PVTT is about 2.7 months. In the past, sorafenib was the only recommended therapy by guidelines with limited effectiveness. This narrative review aimed to describe the current management options for HCC with PVTT. DATA SOURCES: We have reviewed literature from PubMed on the treatment of HCC with PVTT and compiled evidence-based facts on effective therapies available for different types of PVTT. RESULTS: Sorafenib monotherapy is not much effective, but combining it with other methods can improve survival. Each type of PVTT can benefit from the combination of transarterial chemoembolization and sorafenib than sorafenib monotherapy. The tumor downstaging can be realized possibly after transarterial chemoembolization, but tumor invasion into the main trunk of the portal vein greatly impairs efficacy. Although surgery is a curative approach, it is often not recommended for Vp4 PVTT. Some new methods can broaden the indication, but further explorations are needed. Radiotherapy can decrease the possibility of Vp3 progression to Vp4, but building a forecast model of best radiation dose and response is necessary. Systemic chemotherapy, hepatic arterial infusion chemotherapy, radiofrequency ablation, portal stenting, and traditional Chinese medicine are also beneficial in Vp3-4 PVTT. The accurate diagnosis of PVTT can be made by radiomics, and prognostic classification models can be used to design personalized treatments. The application of new treatment methods such as the atezolizumab plus bevacizumab scheme may increase survival. CONCLUSIONS: HCC with PVTT is still a thorny problem, and effective therapeutics need to be explored.

Hierarchy in sensory processing reflected by innervation balance on cortical interneurons.

Sensory processing is subjected to modulation by behavioral contexts that are often mediated by long-range inputs to cortical interneurons, but their selectivity to different types of interneurons remains largely unknown. Using rabies-virus tracing and optogenetics-assisted recording, we analyzed the long-range connections to various brain regions along the hierarchy of visual processing, including primary visual cortex, medial association cortices, and frontal cortices. We found that hierarchical corticocortical and thalamocortical connectivity is reflected by the relative weights of inputs to parvalbumin-positive (PV+) and vasoactive intestinal peptide-positive (VIP+) neurons within the conserved local circuit motif, with bottom-up and top-down inputs preferring PV+ and VIP+ neurons, respectively. Our algorithms based on innervation weights for these two types of local interneurons generated testable predictions of the hierarchical position of many brain areas. These results support the notion that preferential long-range inputs to specific local interneurons are essential for the hierarchical information flow in the brain.

[Effect of placement of peripherally inserted central catheter via the upper versus lower extremity veins: a Meta analysis].

OBJECTIVE: To investigate the effect of placement of peripherally inserted central catheter (PICC) via the upper versus lower extremity veins in neonates through a Meta analysis. METHODS: CNKI, Wanfang Data, VIP Data, CBMdisc, PubMed, Web of Knowledge, Embase, Medline, Cochrane Library and Google Scholar were searched for control studies on the effect of PICC placement via the upper versus lower extremity veins in neonates. RevMan 5.3 was used to perform a Meta analysis of the studies which met the inclusion criteria. RESULTS: A total of 18 studies were included, among which there were 8 randomized controlled trials and 10 cohort studies, with 4 890 subjects in total. Compared with those undergoing PICC placement via the upper extremity veins, the neonates undergoing PICC placement via the lower extremity veins had significantly lower incidence rates of complications (RR=0.83, 95%CI: 0.75-0.92, P<0.05), catheter-related infections (RR=0.77, 95%CI: 0.60-0.99, P<0.05), catheter malposition (RR=0.28, 95%CI: 0.18-0.42, P<0.05), extravasation of the infusate (RR=0.52, 95%CI: 0.40-0.70, P<0.05), and unplanned extubation (RR=0.82, 95%CI: 0.69-0.98, P<0.05). They also had a significantly higher first-attempt success rate of puncture (RR=1.17, 95%CI: 1.05-1.30, P<0.05) and a significantly shorter PICC indwelling time (MD=-0.93, 95%CI: -1.26-0.60, P<0.05). CONCLUSIONS: The above evidence shows that PICC placement via the lower extremity veins has a better effect than PICC placement via the upper extremity veins in neonates.

Effects of the short-term application of pantoprazole combined with aspirin and clopidogrel in the treatment of acute STEMI.

The aim of the present study was to determine the effects of the short-term application of pantoprazole on the co-treatment of acute ST-segment elevation myocardial infarction (STEMI) with aspirin and clopidogrel. A total of 207 acute patients showing primary symptoms of STEMI, who received successful emergent percutaneous coronary intervention treatment during hospitalization were randomly divided into two groups. In the test group proton pump inhibitors (PPIs), the patients were treated with a combination of aspirin and clopidogrel and pantoprazole, while those in the control group were treated only with aspirin and clopidogrel. Gastrointestinal bleeding events and major adverse cardiac events (MACEs) were observed in the two groups. Gastrointestinal bleeding events of the two groups mostly occurred within the first week of hospitalization, although the incidence in the PPIs group was significantly higher than that in the control group (p<0.05). However, no significant difference was observed for the incidence of MACEs between the two groups (p>0.05). In conclusion, the results of the present study have shown that the short-term application of pantoprazole combined with aspirin and clopidogrel does not increase the incidence of MACEs in patients with acute STEMI, reduces the risk of gastrointestinal bleeding, and is thus worth promoting clinically, particularly for high-risk groups.

The impacts of transcatheter occlusion for congenital atrial septal defect on atrial volume, function, and synchronicity in children: a three-dimensional echocardiography study.

OBJECTIVE: To evaluate the impacts of transcatheter closure for atrial septal defect (ASD) on the atria. METHODS: Thirty-four patients with ASD undergoing transcatheter occlusion were recruited in the study, and 34 patients undergoing surgical operation and 34 healthy children were age-matched as controls. A real time three-dimensional (RT3DE) echocardiography was used to measure the volume, function, and synchronicity of the atria. RESULTS: There was no difference in the atrial volume and function between the transcatheter occlusion group and healthy control group (P > 0.05). However, the parameters reflecting the atrial asynchrony were larger in the transcatheter occlusion group (P < 0.05). Compared to the surgical repair group, the transcatheter occlusion group had smaller maximum volume of the left atrium (21.0 +/- 5.2 ml/m(2) vs 24.3 +/- 5.8 ml/m(2), P = 0.01), smaller total emptying volume of the left atrium (12.7 +/- 4.3 ml/m(2) vs 15.1 +/- 3.8 ml/m(2), P = 0.014), smaller total emptying volume of the right atrium (13.5 +/- 5.2 ml/m(2) vs 16.1 +/- 4.7 ml/m(2), P = 0.029), and larger atrial systolic asynchrony indices. CONCLUSIONS: An atrial asynchrony is observed in patients with transcatheter closure of ASD, although little negative impacts on the atrial volume and function are demonstrated, which deserves more attention during follow-up of this specific population.

Value of real-time 3-dimensional echocardiography sectional diagnosis in complex congenital heart disease evaluated by receiver operating characteristic analysis.

OBJECTIVE: We sought to evaluate the value of real-time 3-dimensional (3D) echocardiography (RT-3DE) in the pathologic morphology of complex congenital heart disease (CHD) using receiver operating characteristic (ROC) analysis. METHODS: Thirty patients with complex CHD were examined by 2-dimensional echocardiography (2DE) and RT-3DE. Their diagnoses of pathologic morphology were made by 3 echocardiographers blinded to clinical data. Their value was evaluated by ROC analysis using a 5-point categorical scale in major cardiovascular structures and spatial relationships among complex CHD. RESULTS: Compared with surgical findings, there were 75.6% of the definitely correct in RT-3DE and 64.4% in 2DE. ROC curve for RT-3DE was located left-superior to that for 2DE, and the area under ROC curve for RT-3DE (A = 0.96) was higher than that for 2DE (A = 0.90). There was significant difference between them by the method of Z test (Z = 2.64, P = .0083). CONCLUSIONS: With the spatial 3D display of cardiovascular structural malformations, RT-3DE, coupled with conventional Doppler 2DE, may add information on complex CHD.

[The study of vascular lesion using ultrasound in children with a history of Kawasaki disease].

OBJECTIVE: To explore the endothelial function, carotid artery stiffness index and carotid intima-media thickness in children with a history of Kawasaki disease (KD). METHODS: A cohort of 204 children was studied, which comprised 51 patients with Kawasaki disease with coronary artery lesion (CAL group), 50 patients with Kawasaki disease with normal coronary arteries (normal coronary arteries group), and 103 healthy age matched children (control group). Their systemic blood pressure, fasting cholesterol concentrations, flow-mediated dilation (FMD) of the brachial artery, carotid artery stiffness index and carotid intima-media thickness (IMT) were compared. RESULTS: FMD of the brachial artery in CAL group (5.2% +/- 1.9%) and normal coronary arteries group (6.8% +/- 2.0%) were significantly lower than that of control group (13.2% +/- 4.1%, both P < 0. 01); carotid artery stiffness index in CAL group (4.0 +/- 0.6) was significantly greater than that of normal coronary arteries group (3.6 +/- 0.6) and control group (3.4 +/- 0.5, P = 0.05, P < 0.01); likewise, IMT in CAL group (0.447 mm +/- 0.024 mm) was significantly higher than that of normal coronary arteries group (0.426 mm +/- 0.016 mm) and control group (0.424 mm +/- 0.016 mm, both P < 0.01). In multiple linear regression analysis, age and patient grouping were significant determinants of carotid artery stiffness index, FMD and IMT. There were significant correlations between carotid artery stiffness index, FMD and IMT in both healthy group and KD group after adjustment of age. CONCLUSION: There were endothelial dysfunction and increased systemic arterial stiffness and IMT late after the acute phase of Kawasaki disease. flow-mediated dilation of the brachial artery, carotid artery stiffness index combined carotid intima-media thickness can evaluated completely the prognosis of vascular lesion in convalescence after KD.

Methodological study on real-time three-dimensional echo-cardiography and its application in the diagnosis of complex congenital heart disease.

BACKGROUND: Real-time three-dimensional echocardiography (RT-3DE) has made revolutionized improvements of cardiac imaging during the past few years. However, there is no standard examination method for RT-3DE so far. This study aimed to establish the diagnostic method of RT-3DE and evaluate its application in the diagnosis of complex congenital heart diseases (CHD). METHODS: Fifty patients with complex CHD were examined by RT-3DE with modes of Live 3DE and Full Volume. A series of novel volumetric views combined with Van Praagh sequential segmental approach were introduced to reveal the pathological morphology of the hearts, which were compared with the findings of two-dimensional echocardiography (2DE), angiography and cardiac surgery. RESULTS: In 50 patients, 190 image acquisitions of Full Volume were performed at several acoustic windows including subcostal, apical and parasternal regions. Among them, 94.2% (179/190) of image acquisitions were successful. Most sectional volumetric views could be clearly displayed in 92.6% of the successful image acquisitions. However, sectional volumetric views could not be clearly displayed in 7.4%, which was mainly due to poor perspective conditions of examination location, improper instrument multi-parameter setting and insufficient information of whole heart captured in Full Volume acquisitions. As compared with surgical findings and angiography, RT-3DE made correction to the diagnoses in 2 cases including 1 with corrected transposition of the great arteries and the other with single atrium and mitral cleft. The diagnoses initially made by 2DE for these 2 patients were double outlet right ventricle with transposition of the great arteries and complete atrio-ventricular septal defect. CONCLUSIONS: RT-3DE can clearly display the pathological morphology of complex CHD by a series of novel volumetric views combined with sequential segmental approach through providing more spatial informative cardiovascular structures, which provides a practical method for RT-3DE diagnosis.