Identification of NR3C2 as a functional diagnostic and prognostic biomarker and potential therapeutic target in non-small cell lung cancer.

Background: Non-small cell lung cancer (NSCLC), including the lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) subtypes, is a malignant tumor type with a poor 5-year survival rate. The identification of new powerful diagnostic biomarkers, prognostic biomarkers, and potential therapeutic targets in NSCLC is urgently required. Methods: The UCSC Xena, UALCAN, and GEO databases were used to screen and analyze differentially expressed genes, regulatory modes, and genetic/epigenetic alterations in NSCLC. The UCSC Xena database, GEO database, tissue microarray, and immunohistochemistry staining analyses were used to evaluate the diagnostic and prognostic values. Gain-of-function assays were performed to examine the roles. The ESTIMATE, TIMER, Linked Omics, STRING, and DAVID algorithms were used to analyze potential molecular mechanisms. Results: NR3C2 was identified as a potentially important molecule in NSCLC. NR3C2 is expressed at low levels in NSCLC, LUAD, and LUSC tissues, which is significantly related to the clinical indexes of these patients. Receiver operating characteristic curve analysis suggests that the altered NR3C2 expression patterns have diagnostic value in NSCLC, LUAD, and especially LUSC patients. Decreased NR3C2 expression levels can help predict poor prognosis in NSCLC and LUAD patients but not in LUSC patients. These results have been confirmed both with database analysis and real-world clinical samples on a tissue microarray. Copy number variation contributes to low NR3C2 expression levels in NSCLC and LUAD, while promoter DNA methylation is involved in its downregulation in LUSC. Two NR3C2 promoter methylation sites have high sensitivity and specificity for LUSC diagnosis with clinical application potential. NR3C2 may be a key participant in NSCLC development and progression and is closely associated with the tumor microenvironment and immune cell infiltration. NR3C2 co-expressed genes are involved in many cancer-related signaling pathways, further supporting a potentially significant role of NR3C2 in NSCLC. Conclusions: NR3C2 is a novel potential diagnostic and prognostic biomarker and therapeutic target in NSCLC.

Dual-molecular targeting nanomedicine upregulates synergistic therapeutic efficacy in preclinical hepatoma models.

Advanced hepatocellular carcinoma (HCC) is one of the most challenging cancers because of its heterogeneous and aggressive nature, precluding the use of curative treatments. Sorafenib (SOR) is the first approved molecular targeting agent against the mitogen-activated protein kinase (MAPK) pathway for the noncurative therapy of advanced HCC; yet, any clinically meaningful benefits from the treatment remain modest, and are accompanied by significant side effects. Here, we hypothesized that using a nanomedicine platform to co-deliver SOR with another molecular targeting drug, metformin (MET), could tackle these issues. A micelle self-assembled with amphiphilic polypeptide methoxy poly(ethylene glycol)-block-poly(L-phenylalanine-co-l-glutamic acid) (mPEG-b-P(LP-co-LG)) (PM) was therefore designed for combinational delivery of two molecular targeted drugs, SOR and MET, to hepatomas. Compared with free drugs, the proposed, dual drug-loaded micelle (PM/SOR+MET) enhanced the drugs' half-life in the bloodstream and drug accumulation at the tumor site, thereby inhibiting tumor growth effectively in the preclinical subcutaneous, orthotopic and patient-derived xenograft hepatoma models without causing significant systemic and organ toxicity. Collectively, these findings demonstrate an effective dual-targeting nanomedicine strategy for treating advanced HCC, which may have a translational potential for cancer therapeutics. STATEMENT OF SIGNIFICANCE: Treatment of advanced hepatocellular carcinoma (HCC) remains a formidable challenge due to its aggressive nature and the limitations inherent to current therapies. Despite advancements in molecular targeted therapies, such as Sorafenib (SOR), their modest clinical benefits coupled with significant adverse effects underscore the urgent need for more efficacious and less toxic treatment modalities. Our research presents a new nanomedicine platform that synergistically combines SOR with metformin within a specialized diblock polypeptide micelle, aiming to enhance therapeutic efficacy while reducing systemic toxicity. This innovative approach not only exhibits marked antitumor efficacy across multiple HCC models but also significantly reduces the toxicity associated with current treatments. Our dual-molecular targeting approach unveils a promising nanomedicine strategy for the molecular treatment of advanced HCC, potentially offering more effective and safer treatment alternatives with significant translational potential.

Association between vitamin B2 intake and prostate-specific antigen in American men: 2003-2010 National Health and Nutrition Examination Survey.

BACKGROUND: Accumulating evidence suggests a pivotal role of vitamin B2 in the pathogenesis and progression of prostate cancer (PCa). Vitamin B2 intake has been postulated to modulate the screening rate for PCa by altering the concentration of prostate-specific antigen(PSA). However, the relationship between vitamin B2 and PSA remains indeterminate. Hence, we conducted a comprehensive evaluation of the association between vitamin B2 intake and PSA levels, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: From a pool of 20,371 participants in the NHANES survey conducted between 2003 and 2010, a cohort of 2,323 participants was selected for the present study. The male participants were classified into four distinct groups based on their levels of vitamin B2 intake. We employed a multiple linear regression model and a non-parametric regression method to investigate the relationship between vitamin B2 and PSA levels. RESULTS: The study cohort comprised of 2,323 participants with a mean age of 54.95 years (± 11.73). Our findings revealed a statistically significant inverse correlation between vitamin B2 intake (mg) and PSA levels, with a reduction of 0.13 ng/ml PSA concentration for every unit increase in vitamin B2 intake. Furthermore, we employed a fully adjusted model to construct a smooth curve to explore the possible linear relationship between vitamin B2 intake and PSA concentration. CONCLUSIONS: Our study in American men has unveiled a notable inverse association between vitamin B2 intake and PSA levels, potentially posing a challenge for the identification of asymptomatic prostate cancer. Specifically, our findings suggest that individuals with higher vitamin B2 intake may be at a greater risk of being diagnosed with advanced prostate cancer in the future, possibly indicating a detection bias. These results may offer a novel explanation for the observed positive correlation between vitamin B2 intake and prostate cancer.

Esculin suppresses the PERK-eIF2α-CHOP pathway by enhancing SIRT1 expression in oxidative stress-induced rat chondrocytes, mitigating osteoarthritis progression in a rat model.

OBJECTIVE: Osteoarthritis (OA) is a degenerative disease characterized by the gradual degeneration of chondrocytes, involving endoplasmic reticulum (ER) stress. Esculin is a natural compound with antioxidant, anti-inflammatory and anti-tumor properties. However, its impact on ER stress in OA therapy has not been thoroughly investigated. We aim to determine the efficiency of Esculin in OA treatment and its underlying mechanism. METHODS: We utilized the tert-butyl hydroperoxide (TBHP) to establish OA model in chondrocytes. The expression of SIRT1, PERK/eIF2α pathway-related proteins, apoptosis-associated proteins and ER stress-related proteins were detected by Western blot and Real-time PCR. The apoptosis was evaluated by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. X-ray imaging, Hematoxylin & Eosin staining, Safranin O staining and immunohistochemistry were used to assess the pharmacological effects of Esculin in the anterior cruciate ligament transection (ACLT) rat OA model. RESULTS: Esculin downregulated the expression of PERK/eIF2α pathway-related proteins, apoptosis-associated proteins and ER stress-related proteins, while upregulated the expression of SIRT1 and Bcl2 in the TBHP-induced OA model in vitro. It was coincident with the results of TUNEL staining and flow cytometry. We further confirmed the protective effect of Esculin in the rat ACLT-related model. CONCLUSION: Our results suggest the potential therapeutic value of Esculin on osteoarthritis. It probably inhibits the PERK-eIF2α-ATF4-CHOP pathway by upregulating SIRT1, thereby mitigating endoplasmic reticulum stress and protecting chondrocytes from apoptosis.

Brucellosis involving the aorta and iliac arteries: a systematic review of 130 cases.

Objective: Brucellosis, the most common bacterial zoonosis, poses a serious threat to public health in endemic regions. Cardiovascular complications of brucellosis, mostly pericarditis or endocarditis, are the leading cause of brucellosis-related death. Complications involving the aorta and iliac arteries are extremely rare but can be life-threatening. Our objective was to identify and review all reported cases of aortic and iliac involvement in brucellosis to provide a deep, up-to-date understanding of the clinical characteristics and management of the disease. Methods: Online searches in PubMed, Web of Science, China National Knowledge Infrastructure, and the Chinese Wanfang database were conducted to collect articles reporting cases of brucellosis with aortic and iliac artery involvement. All data in terms of patient demographics, diagnostic methods, clinical manifestations, and treatment regimens and outcomes were extracted and analyzed in this systematic review. Results: A total of 79 articles were identified, reporting a total of 130 cases of brucellosis with aortic and iliac artery involvement. Of the 130 cases, 110 (84.5%) were male individuals and 100 (76.9%) were over 50 years old. The patients had an overall mortality rate of 12.3%. The abdominal aorta was most commonly involved, followed by the ascending aorta, iliac artery, and descending thoracic aorta. Arteriosclerosis, hypertension, and smoking were the most common comorbidities. There were 71 patients (54.6%) who presented with systemic symptoms of infection at the time of admission. Endovascular therapy was performed in 56 patients (43.1%), with an overall mortality rate of 3.6%. Open surgery was performed in 52 patients (40.0%), with an overall mortality rate of 15.4%. Conclusion: Aortic and iliac involvement in brucellosis is extremely rare but can be life-threatening. Its occurrence appears to be associated with the male gender, an older age, arteriosclerosis, and smoking. Although the number of reported cases in developing countries has increased significantly in recent years, its incidence in these countries may still be underestimated. Early diagnosis and therapeutic intervention are critical in improving patient outcomes. Endovascular therapy has become a preferred surgical treatment in recent years, and yet, its long-term complications remain to be assessed.

The cytotoxicity of γδT cells in non-small cell lung cancer mediated via coordination of the BCL-2 and AKT pathways.

The effectiveness and mechanisms of γδT-cell immunotherapy in lung cancer remain unclear. In this study, we assessed the effects of continuous, low-dose γδT-cell intervention on lung cancer cells. We cultured γδT cells with a lung cancer cell line (A549) and replaced the γδT-cell population every 48 hours. The killing effect of γδTcells on A549 cells and the Half-maximal inhibitory concentration (IC50) value were detected by the cholecystokinin octapeptide (CCK-8) method. The levels of perforin, granzyme B and the inflammatory factors interleukin-6 (IL-6), interferon (IFN)-γ, and tumor necrosis factor-alpha (TNF-a), in the supernatants of cocultured cells were measured by ELISA. The protein expression of Bcl-2, Bax, PI3K and Akt was detected by western blotting. Our results indicated that γδT-cell treatment decreased the protein expression of Bcl-2, PI3K, and AKT but upregulated that of Bax. Moreover, γδT-cell treatment increased perforin and granzyme B release related to the Bax/Bcl-2 signaling pathway. In addition, γδT-cell-mediated cytolysis for A549 cells involved the PI3K/AKT pathway. In vivo results were consistent with the in vitro results. γδT-cell immunotherapy integrated regulation of a signaling pathway network involving the mutual regulation of apoptosis and proliferation. γδT-cell immunotherapy could be used to enhance the cytotoxic killing of lung cancer cells.

Clinical effect of endovascular repair of complex aortic lesions using optimized Octopus surgery.

Objective: Complex aortic lesions, especially those involving branches of the visceral artery, remain a challenge to treat. A single-center study using the Octopus technique to evaluate the safety and short-term effects of endovascular repair of complex aortic lesions was reported and documented. Methods: The data of six cases who underwent optimized Octopus surgery in our center from August 2020 to February 2022 were analyzed retrospectively. The choice of operation scheme, operation time, operation complications, and follow-up data were analyzed among them. Results: The average age of the six patients undergoing optimized Octopus surgery was 55.1 ± 17.2 years. Two cases were diagnosed as pararenal aortic aneurysms; four cases were aortic dissection involving the visceral artery. All cases achieved technical success; all visceral arteries were reconstructed as planned. A total of 17 visceral arteries were planned to be reconstructed; five celiac arteries were embolized. Three cases of gutter endoleak were found during the operation without embolization but with follow-up observation. There were two cases of slight damage to renal function and two cases of perioperative death. Other complications, such as intestinal ischemia and spinal cord ischemia, did not occur. Follow-up ranged from 6 months to 30 months. One patient died of gastrointestinal bleeding 6 months after the operation. At the 6 months follow-up, computed tomographic angiography showed that all internal leaks had disappeared. The patency rate of the visceral artery was 100%, and no complications, such as stent displacement and occlusion, occurred during the follow-up period. Conclusion: With fenestrated and branched stent grafts technology not widely available, and off label use not a viable option, Octopus technology for treating complex aortic lesions should be considered. The Octopus technique is an up-and-coming surgical method, but we should recognize its operation difficulty, operation-related complications, and long-term prognosis. We should pay attention to and continue to optimize Octopus technology.

Human descending aorta injury caused by brucellosis: A case report.

BACKGROUND: Brucellosis is one of the most common zoonotic diseases in the world. Although cardiovascular complications of human brucellosis account for only 3% of morbidity, they are the leading cause of death. Peripheral vascular disease due to brucellosis is rare and under-reported in the literature. CASE PRESENTATION: Two patients with previous brucellosis, both of whom had been treated with anti-brucellosis, were admitted to vascular surgery for thoracic aortic ulcer and abdominal aortic pseudoaneurysm, respectively, with positive IgG antibody to brucellosis and negative IgM antibody to brucellosis, tube agglutination test, and blood culture. These 2 patients were successfully treated with aortic stent-graft implantation and followed up for 8 and 10 weeks without complications. CONCLUSIONS: Chronic damage to human blood vessels by brucellosis may not disappear with brucellosis treatment, and peripheral blood vessels should be examined annually in people previously diagnosed with brucellosis. Clinicians in related departments should pay attention to peripheral vascular complications of brucellosis.

Immunosuppressive adenosine-targeted biomaterials for emerging cancer immunotherapy.

Immunotherapy has paved the way for the future of cancer therapy, but there are still significant challenges to be overcome, such as the occurrence of immune escape or suppression. Adenosine is essential in modulating the immune responses of immune cells and maintaining immune tolerance. Emerging adenosine pathway inhibitors are considered a breakthrough in cancer immunotherapy, with emphasis first being placed on the top-down blockade of adenosine signaling axis, followed by combination therapy. However, these therapeutic strategies rely on adenosine inhibitors, mainly small molecules or antibody proteins, which are limited by a single route of administration and off-target toxicity. Therefore, synergistic nanomedicine with accurate delivery targeting deeper tumors is focused on in preclinical studies. This review discusses how adenosine reshapes immunosuppressive microenvironments through its effects on immune cells, including lymphocytes and myeloid cells. Additionally, it will be the first discussion of a comprehensive strategy of biomaterials in modulating the adenosine signaling pathway, including inhibition of adenosine production, inhibition of adenosine binding to immune cells, and depletion of adenosine in the microenvironments. Furthermore, biomaterials integrating multiple therapeutic modalities with adenosine blocking are also discussed as a promising strategy for promoting cancer immunotherapy.

Surgical Treatment of Recurrent Spheno- Orbital Meningioma.

OBJECTIVE: The extensive bone infiltration and carpet-like growth characteristics of spheno-orbital meningioma (SOM) make it hard to remove entirely, and recurrence and proptosis are the main reasons for reoperation. The authors report 20 cases of surgical treatment for recurrence of SOM, including surgical technique and symptom improvement. METHODS: The clinical data and follow-up results of 20 cases of recurrent SOM at our institution from 2000 to 2017 were retrospectively analyzed. RESULTS: All of the 20 patients with recurrence had received at least one operation before admission, with a mean age of 56 years and 70% female. The mean follow-up time was 36 months (172 months). All patients mainly showed symptoms such as proptosis and headache, and were found to be affected by supraorbital fissure during the operation. in 17 patients with recurrence, the affected sphenoid wing became tumor-like hyperplasia. Patients with extraocular muscle involvement have obvious protrusion and are often accompanied by diplopia. After surgical removal of the tumor, the symptoms of proptosis in 19 patients were significantly improved. During the follow-up, only 3 cases of proptosis recurred. After 15 patients underwent Simpson grade IV resection, 4 patients (27%) relapsed again. Five patients underwent Simpson III resection, and only 1 patient (20%) had tumor recurrence 18th months after surgery, and no proptosis recurred. CONCLUSIONS: The complete surgical removal of recurrent SOM is practically impossible. The main direction of surgical treatment should be to improve the symptoms of proptosis.

Case Report: A Pseudoaneurysm Involving the Left Common Iliac Artery Secondary to Brucellosis: A Rare Case Report.

Pseudoaneurysms of the common iliac artery caused by Brucellosis are exceedingly uncommon. Infected common iliac artery pseudoaneurysms, particularly those caused by brucellosis, are more difficult to diagnose and cure than general pseudoaneurysms. The risk of mortality is significantly high in this condition. Nonsurgical treatment of a brucellosis-induced common iliac artery pseudoaneurysm is futile, and it should be operated on as soon as feasible. Long-term and multi-course antibacterial therapy with combination antibiotics is required. For the treatment of Brucella-infected pseudoaneurysms, endovascular surgery can be both effective and safe.

IRF7 as an Immune-Related Prognostic Biomarker and Associated with Tumor Microenvironment in Low-Grade Glioma.

PURPOSE: Tumor microenvironment (TME) affects the occurrence and progression of low-grade glioma (LGG). The aim of this study is to identify TME-related genes that influence prognosis in LGG patients and to explore their function and role in tumor immunity. PATIENTS AND METHODS: The TME components of LGG samples in the Cancer Genome Atlas (TCGA) database were identified by the ESTIMATE method, and differentially expressed genes (DEGs) with significant differences in immune scores and stromal scores were screened out. The core genes of DEGs were screened out by protein-protein interaction (PPI) network. Furthermore, immune-related target genes significantly correlated with prognosis were identified. Survival analysis and correlation analysis showed the correlation between target genes and clinical features and prognosis. The expression differences of target genes were verified by external database Chinese Glioma Genome Atlas (CGGA). CIBERSORT software identified the proportion of tumor-infiltrating immune cells (TICs) that were significantly related to target genes. Gene set enrichment analysis (GSEA) could enrich the main functions related to high and low expression of target genes. RESULTS: A total of 1567 DEGs were screened out from 529 LGG samples in the TCGA database, and 146 immune-related genes affecting prognosis were found. A total of 403 core genes were obtained from PPI network. The target gene interferon regulatory factor 7 (IRF7) was significantly associated with prognosis and clinical features of the tumor. The CGGA database verified the relationship between high and low expression groups of IRF7 and prognosis. GSEA indicated that IRF7 was mainly enriched in immune-related activities, significantly correlated with T cells CD8, macrophages M1, macrophages M2 and monocytes. CONCLUSION: The IRF7 is involved in immune responses in TME of LGG, which in turn influenced tumor occurrence and progression. IRF7 can act as a potential biomarker for prognosis in patients with LGG and provide a target for tumor immunotherapy.

Subdural fluid collection rather than meningitis contributes to hydrocephalus after cervical laminoplasty: A case report.

BACKGROUND: Hydrocephalus following dural tear after spinal surgery is rare. Although a few cases of obstructive hydrocephalus caused by subdural fluid collection and communicating hydrocephalus associated with meningitis have been reported, the mechanism remains uncertain. Herein we describe a patient complicated with hydrocephalus after cervical laminoplasty in whom subdural fluid collection in the cervical spine and posterior cranial fossa rather than chronic meningitis was the main mechanism. CASE SUMMARY: A 45-year-old man underwent cervical laminoplasty for cervical spondylotic myelopathy at a local hospital. Ten days postoperatively, a high fever occurred and magnetic resonance imaging (MRI) showed cerebrospinal fluid (CSF) leakage. Pseudomeningocele liquid test showed high levels of protein and white blood cell (WBC) count with negative bacterial culture. The patient was treated with short-term intravenous antibiotic and discharged with normal body temperature. The patient was uneventful during the first 8 mo follow-up although repeated MRI showed persistent pseudomeningocele. At the 9th mo postoperatively, the patient gradually presented with dizziness and headache accompanied by recurrent weakness of his left arm. Imaging examinations demonstrated hydrocephalus and a cystic lesion around the cervical spinal cord. CSF test from lumbar puncture indicated chronic meningitis. MRI on 1 d after pseudomeningocele drainage showed a significant decrease in the cystic volume, suggesting that the cystic lesion would be subdural fluid collection rather than adhesive arachnoiditis. After dural defect repair, the patient's symptoms completely resolved and hydrocephalus gradually disappeared. CSF analysis at the 21-mo follow-up revealed significantly decreased protein level and WBC count. CONCLUSION: Subdural fluid collection rather than meningitis contributes to the hydrocephalus formation after cervical laminoplasty.

Modified porous microstructure for improving bone compatibility of poly-ether-ether-ketone.

Poly-ether-ether-ketone (PEEK) has been the promising implantation material since it was first applied in the medical field in the 1990s. With its irreplaceable advantages, such as high mechanical and biological properties, human-like tensile strength and elastic modulus, and excellent physical and chemical stability, PEEK has been regarded as an excellent implantation material, and has been widely used in orthopedics, reconstructive surgery, and dentistry. However, PEEK also has an obvious shortcoming of poor bone compatibility due to its inherent hydrophobicity and bio-inertia, which is a great challenge for its prospect. In the present study, based on the acknowledged fact that enhancing the roughness of PEEK can improve its bone compatibility, modified porous PEEK implants with different porosities (40%, 50%, 60% and solid) were fabricated by Fused Deposition Modeling (FDM), and experiments in vitro and in vivo were conducted to determine whether the bone compatibility can be improved, and compare the biological properties between different porosities. These results indicate that both in vitro and in vivo, the bone compatibility of the modified porous PEEK has been strongly improved, when compared to the control group (solid PEEK implants). In vitro and in vivo, the 40%-porosity-PEEK possessed the highest bone compatibility.

Cystic Adventitial Disease of the Common Femoral Artery: A Rare-Case Report.

Herein, we report the case of a 59-year-old man with intermittent claudication of ~100 m, who complained of resting pain in his lower right extremity. A pelvic, contrast-enhanced, computed tomography scan showed the presence of cystic density in the lower segment of the right common femoral artery. Faced with the risk of acute limb ischemia, we navigated a challenging diagnostic procedure to choose an appropriate treatment for him. Additionally, we performed a pathological investigation of the excised common femoral artery following the excision bypass. On postoperative day 5, the patient was discharged from the hospital. During the 2-year follow-up, no new cysts were discovered, and the patient had favorable prognosis.

Diagnostic nomogram model for predicting preoperative pathological grade of meningioma.

BACKGROUND: Meningioma is the most common primary tumor of the central nervous system. Preoperative diagnosis of high-grade meningioma is helpful for the selection of treatment options. The aim of our study is to establish a diagnostic nomogram model for preoperative prediction of the pathological grade of meningioma. METHODS: The predictive model was established from a cohort of 215 clinicopathologically confirmed meningioma between January 2012 and December 2017. Radiomic features were collected from preoperative magnetic resonance imaging (MRI) and computed tomography of patients with meningioma. The least absolute shrinkage and selection operator (LASSO) regression model was used for data dimension reduction and feature selection. Multivariate logistic regression was used to build a predictive model and presented as a nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal validation was evaluated using bootstrapping validation. RESULTS: High-grade meningioma was observed in 47 patients (22%). The predictors included in the nomogram were tumor-brain interface, bone invasion, and tumor location. The final diagnostic model exhibited good calibration and discrimination with a C-index of 0.874 (95% confidence interval: 0.818-0.929) and a higher C-index of 0.868 in internal validation. Decision curve analysis (DCA) indicated that the nomogram is very useful in clinical practice. CONCLUSIONS: This study provides a nomogram model with tumor-brain interface, bone invasion, and tumor location that can effectively predict the preoperative pathological grading of patients with meningioma and thus help clinicians provide more reasonable treatment strategies for meningioma patients.

Comparison of surgical clipping and endovascular coiling in the treatment of oculomotor nerve palsy caused by posterior communicating artery aneurysm.

Oculomotor nerve palsy (ONP) caused by posterior communicating aneurysm (PcomAA) is mainly treated by surgical clipping or endovascular coiling. However, there are still some controversies about which treatment method could provide the more beneficial prognosis. This study aimed to compare ONP recovery rate between surgical clipping and endovascular coiling in patients diagnosed as PcomAA combined with ONP, and explore the potential risk factors of ONP recovery.The clinical data of 152 patients with ONP caused by PcomAA were retrospectively analyzed. Diameter of aneurysm, different treatment methods (surgical clipping or endovascular coiling), subarachnoid hemorrhage (SAH), degree of preoperative ONP, time from ONP onset to treatment, as well as degree of ONP symptom recovery were collected from medical records. All patients were followed up for at least 1 year.One hundred twelve patients underwent surgical clipping and 40 patients received endovascular coiling. There were no significant differences in age, gender, aneurysm diameter, hypertension, dyslipidemia, time from ONP symptom onset to treatment, SAH, and preoperative ONP degree between the 2 groups (all P > .05). Time to complete or partial recovery was 86.7 ±â€Š35.7 days for patients receiving surgical clipping and 132.6 ±â€Š37.5 days for patients receiving endovascular coiling, respectively (Log rank test, P < .001). The recovery rate was 94.6% in the surgical clipping group and 65.0% in the endovascular coiling group. The difference between the two groups was statistically significant (P < .001). Postoperative ONP recovery in the surgical clipping group was significantly superior to that of patients in the endovascular coiling group (HR, 2.625; 95% CI: 1.423-4.841; P = .002). Time from ONP symptom onset to treatment exerted the obvious effect on the ONP prognosis (HR, 0.572; 95% CI: 0.384-0.852; P = .006). In addition, the ONP recovery in patients with SAH before surgery was also independently associated with ONP prognosis (HR, 1.276; 95% CI, 1.043-1.562; P = .018). There was no treatment-related death in either group, and postoperative complications were within the manageable range.The recovery rate and recovery degree of ONP after surgical clipping was significantly better than that of endovascular coiling in PcomAA patients combined with ONP. The postoperative ONP recovery was associated with preoperative spontaneous SAH and time from ONP onset to treatment.

LEF1-AS1 accelerates tumorigenesis in glioma by sponging miR-489-3p to enhance HIGD1A.

Long non-coding (lncRNA) lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) has been validated to be implicated in manifold cancers, whereas its function in glioma has not been understood thoroughly. Hence, in this study, we tested that LEF1-AS1 expression was significantly upregulated in glioma tissues and cell lines. Besides, knockdown of LEF1-AS1 repressed cell proliferation while activated apoptosis in glioma cells in vitro, and also suppressed tumor growth in vivo. RNA pull-down and luciferase reporter assays affirmed that LEF1-AS1 could bind with miR-489-3p. In addition, miR-489-3p expression was downregulated in glioma cells. Moreover, miR-489-3p depletion partly offset LEF1-AS1 knockdown-mediated function on proliferation and apoptosis. Further, HIGD1A identified as the target gene of miR-489-3p was upregulated in glioma cells. HIGD1A silence could restrict the process of glioma. In rescue assays, upregulation of HIGD1A remedied the inhibitory impacts of LEF1-AS1 silence on glioma cell growth. In summary, our studies corroborated the regulatory mechanism of LEF1-AS1/miR-489-3p/HIGD1A axis in glioma, suggesting that targeting LEF1-AS1 might be a promising method for glioma therapy in the future.

LncRNA-XIST/microRNA-126 sponge mediates cell proliferation and glucose metabolism through the IRS1/PI3K/Akt pathway in glioma.

Abnormal glucose metabolism may contribute to cancer progression. Glioma represents a cancer resulting from an imbalance between glucose metabolism and tumor growth. However, the molecular mechanisms responsible for dysregulated brain glucose metabolism and lactate accumulation in glioma remain to be elucidated. The present study identified a long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) as a candidate to mediate glucose metabolism in glioma. Cell viability, migration, invasion, and resistance to apoptosis were evaluated in lncRNA-XIST-depleted glioblastoma cells by short hairpin RNA. Glucose uptake, lactate production, as well as levels of glucose transporter 1 (GLUT1) and GLUT3, were measured. Luciferase assay, RNA pull-down, and RNA immunoprecipitation were performed to validate the interactions among lncRNA-XIST, microRNA-126 (miR-126), and insulin receptor substrate 1 (IRS1). An in vivo analysis was carried out in nude mice bearing glioblastoma cell xenografts. The study found that lncRNA-XIST knockdown inhibited cell viability, migration, invasion, resistance to apoptosis, and glucose metabolism of glioblastoma cells. LncRNA-XIST functioned as a competing endogenous RNA of miR-126 and then regulated IRS1/PI3K/Akt pathway in glioblastoma cells. In vivo results demonstrated lncRNA-XIST knockdown reduces the tumorigenicity of glioblastoma cells. Taken together, we demonstrated a novel cellular mechanism that was dependent of the lncRNA-XIST/miR-126/IRS1/PI3K/Akt pathway in enhanced glucose metabolism in glioma.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio Are Effective Predictors of Prognosis in Patients with Acute Mesenteric Arterial Embolism and Thrombosis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been shown to be valuable prognostic markers for a variety of pathological conditions including solid tumors, sepsis, and others. However, the prognostic values of the NLR and PLR in patients with acute mesenteric arterial embolism (AMAE) and acute mesenteric arterial thrombosis (AMAT) have not been elucidated. The aim of this study was to determine the predictive value of the NLR and PLR for poor prognosis in patients with AMAE and AMAT. METHODS: A total of 137 patients with AMAE (n = 77) or AMAT (n = 60) were divided into a poor outcome group (cases of intestinal necrosis or death) and a better outcome group (cases without intestinal necrosis who survived successfully), according to prognosis. Neutrophil, platelet, and lymphocyte counts were recorded before pharmacotherapy or surgery. The NLR and PLR were calculated, and logistic regression analysis was performed to test their prognostic values. RESULTS: The cutoff values for NLR and PLR were 11.05 and 156.26, respectively. The PLR was linearly associated with the NLR (R = 0.769, P < 0.001). NLR (odds ratio [OR] = 6.835, 95% confidence interval [CI] = 2.282-20.469, P = 0.001), PLR (OR = 4.871, 95% CI = 1.627-14.587, P = 0.005), and coronary heart disease (OR = 3.388, 95% CI = 1.156-9.929, P = 0.026) were found to be independent prognostic factors for the patients. CONCLUSIONS: NLR ≥ 11.05, PLR ≥ 156.26, and coronary heart disease were shown to be risk factors for poor prognosis in patients with AMAE and AMAT. According to these factors, patients can be divided into 3 prognostic groups: good, NLR < 11.05 with PLR < 156.26; moderate, NLR < 11.05 with PLR ≥ 156.26 or NLR ≥ 11.05 with PLR < 156.26; and poor, NLR ≥ 11.05 with PLR ≥ 156.26.