Association of diarrhea or constipation with urinary incontinence in adults: A cross-sectional analysis of the National Health and Nutrition Examination Survey.

AIMS: This study aimed to investigate the association between diarrhea or constipation and urinary incontinence (UI) in adults. METHODS: Data from the National Health and Nutrition Examination Survey for 2009-2010 was used to include 4686 adults aged 20 and over in the analysis. Stress urinary incontinence (SUI) and urgency urinary incontinence (UUI) were used as outcome variables, with diarrhea and constipation as exposure factors. We first compared the baseline characteristics of those with and without SUI, as well as those with and without UUI. The impact of diarrhea or constipation on SUI and UUI was assessed using multivariate logistic regression models. To ensure the stability of the results, subgroup and stratified analyses were conducted. RESULTS: The prevalence rates of UUI and SUI were 22.49% and 23.39%, respectively. Adjusted multivariate logistic regression analysis revealed that the risk of UUI was increased by either diarrhea (OR 1.66, 95% CI 1.36-2.04) or constipation (OR 1.42, 95% CI 1.11-1.83). The risk of SUI was also elevated by either diarrhea (OR 1.36, 95% CI 1.11-1.67) or constipation (OR 1.32, 95% CI 1.06-1.63). Subgroup analysis revealed no significant differences in the interaction tests between constipation or diarrhea and UI. CONCLUSIONS: This study found that both constipation and diarrhea increase the risk of UUI and SUI.

The role of China in protecting the Arctic against pollutions from vessels: a legal perspective.

In the past decade, global climate change and the rapid melting of polar ice have dramatically transformed the Arctic landscape from a vast ice-covered area to a seasonally navigable sea. This accessibility has sparked increased commercial activity, posing a threat from various pollutants, particularly from vessel sources. Given China's profound interests in Arctic shipping, its involvement may face resistance from Arctic states, and therefore, it is important for China to ensure that its presence benefits local communities and states. This study explores China's role in shaping the international legal landscape to protect the Arctic from vessel-source pollutions. The intricate interplay between China's economic interests, maritime security concerns, and environmental commitments in the Arctic underscores China's potential role. By aligning with existing international legal structures, such as UNCLOS and MARPOL, China has already started to demonstrate its commitment to preserving the Arctic environment. This study assesses and discusses the potentially strategic importance of China's involvement in influencing legal regimes, offering a crucial contribution to global efforts to preserve this vital region.

The immune response to arterial damage in a mouse model of intermittent hypoxia: a transcriptomics analysis.

PURPOSE: Mice can develop arterial damage and even atherosclerosis under intermittent hypoxia (IH); however, the specific mechanism of arterial damage induced by IH remains unclear. Hence, this research aimed to illustrate the underlying mechanism linking IH to arterial injury. MATERIALS AND METHODS: The differential gene expression of the thoracic aorta under normoxia or IH mice was analyzed utilizing RNA sequencing. Furthermore, GO, KEGG pathway, and CIBERSORT analyses were carried out. For verification of the expression of candidate genes affected by IH, quantitative RT-qPCR (qRT-PCR) was conducted. Immunohistochemical (IHC) staining revealed immune cell infiltration in the thoracic aorta. RESULTS: The thickness of the intima-media of the mouse aorta was increased, and the fiber structure was disordered under IH. Transcriptomics analysis showed that in the aorta, 1137 upregulated genes and 707 downregulated genes were affected by IH, significantly related to the activation of the immune system and cell adhesion. Furthermore, B cell infiltration around the aorta was observed under IH. CONCLUSIONS: IH might lead to structural changes in the aorta by activating the immune response and enhancing cell adhesion.

Genome-Wide Association Study of Obstructive Sleep Apnea and Objective Sleep-related Traits Identifies Novel Risk Loci in Han Chinese Individuals.

Rationale: Previous genetic studies of obstructive sleep apnea (OSA) have limitations in terms of precise case definition, integrated quantitative traits, and interpretation of genetic functions; thus, the heritability of OSA remains poorly explained. Objectives: To identify novel genetic variants associated with OSA and objective sleep-related traits and to explore their functional roles. Methods: A genome-wide association study was performed in 20,590 Han Chinese individuals (5,438 OSA and 15,152 control samples). Human samples and point mutation knockin mice were used for follow-up investigation of gene functions. Measurements and Main Results: Two characteristic study-wide significant loci (P < 2.63 × 10-9) for OSA were identified: the PACRG intronic variant rs6455893 on 6q26 (odds ratio [OR] = 1.62; 95% confidence interval [CI], 1.39-1.89; P = 6.98 × 10-10) and the missense variant rs3746804 (p.Pro267Leu) in the riboflavin transporter SLC52A3 on 20p13 (OR = 0.83; 95% CI, 0.79-0.88; P = 7.57 × 10-10). In addition, 18 genome-wide significant loci associated with quantitative OSA and objective sleep-related traits were identified, 5 of which exceeded the study-wide significance threshold. Rs3746804 was associated with elevated serum riboflavin concentrations, and the corresponding mutation in mice increased riboflavin concentrations, suggesting that this variant may facilitate riboflavin uptake and riboflavin-dependent physiological activity. Conclusions: We identified several novel genome-wide significant loci associated with OSA and objective sleep-related traits. Our findings provide insight into the genetic architecture of OSA and suggest that SLC52A3 might be a therapeutic target, whereas riboflavin might be a therapeutic agent.

Emerging functions of circular RNA in the regulation of adipocyte metabolism and obesity.

As noncoding RNAs, circular RNAs (circRNAs) are covalently enclosed endogenous biomolecules in eukaryotes that have tissue specificity and cell specificity. circRNAs were once considered a rare splicing byproduct. With the development of high-throughput sequencing, it has been confirmed that they are expressed in thousands of mammalian genes. To date, only a few circRNA functions and regulatory mechanisms have been verified. Adipose is the main tissue for body energy storage and energy supply. Adipocyte metabolism is a physiological process involving a series of genes and affects biological activities in the body, such as energy metabolism, immunity, and signal transmission. When adipocyte formation is dysregulated, it will cause a series of diseases, such as atherosclerosis, obesity, fatty liver, and diabetes. In recent years, many noncoding RNAs involved in adipocyte metabolism have been revealed. This review provides a comprehensive overview of the basic structure and biosynthetic mechanism of circRNAs, and further discusses the circRNAs related to adipocyte formation in adipose tissue and liver. Our review will provide a reference for further elucidating the genetic regulation mechanism of circRNAs involved in adipocyte metabolism.

Multiple genetic variations of chronic rhinosinusitis with nasal polyps are associated with respiratory parameters in men with obstructive sleep apnea.

PURPOSE: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a higher risk of obstructive sleep apnea (OSA). However, the relationship between CRSwNP and OSA remains unclear. The aim of this research study was to evaluate the association of multiple single nucleotide polymorphism (SNP) variations in CRSwNP with sleep- and breath-related parameters in men with OSA. METHODS: We included eight CRSwNP SNPs in 2320 participants after strict screening. For each participant, the genetic risk score (GRS) was calculated based on the cumulative effect of multiple genetic variants of CRSwNP. A bivariate correlation analysis was used to assess the relationship between CRSwNP genetic polymorphisms and polysomnography parameters in men with OSA. Logistic regression analyses were used to assess the relationship between the risk of OSA and CRSwNP genetic polymorphisms. RESULTS: In moderate OSA, rs28383314 was related to the oxygen desaturation index, and rs4807532 was positively associated with the microarousal index (r = 0.09, P = 0.03 and r = 0.11, P = 0.01, respectively). The CRSwNP GRS was positively correlated with the oxygen desaturation index and cumulative time percentage with SpO2 < 90% in moderate OSA (r = 0.13, P < 0.001 and r = 0.1, P = 0.01, respectively). There was no association between the CRSwNP GRS and the risk of OSA (OR = 1.007; 95% CI, 0.973-1.042; P = 0.702). CONCLUSION: In men with moderate OSA, single CRSwNP genetic variations correlated with sleep-related parameters, and the cumulative effects of CRSwNP genetic variations were associated with the hypoxic index. CRSwNP may be a predisposing condition for sleep disorders in men with moderate OSA.

Role of miR-490-3p in blocking bladder cancer growth through targeting the RNA-binding protein PCBP2.

MiR-490-3p is regarded as a tumor suppressor in many cancers, but whether miR-490-3p is involved in the development of bladder cancer remains unknown. BALB/c nude mice (male, 15-20 g) were used to investigate the role of MiR-490-3p in bladder cancer. The relationship between miR-490-3p and PCBP2 involved in bladder cancer regulation were determined. Cell viability, proliferation, and cell cycle were estimated by cell counting kit-8 (CCK-8) assay, 5-bromo-2'-deoxyuridine (BrdU) detection, and flow cytometry analysis, respectively. In animal experiments, lentivirus was transfected into bladder cancer cells to overexpress miR-490-3p, which were then injected into mice and the change of tumor volume was assessed. Principal findings: The expression of MiR-490-3p was decreased in bladder cancer cells. Overexpression of miR-490-3p inhibited bladder cancer cell viability and proliferation. Moreover, overexpression of miR-490-3p caused cell cycle arrest in bladder cancer cells. The inhibitory effect of miR-490-3p on bladder cancer cells growth could be counteracted by enhancing PCBP2 expression. In vivo, bladder cancer growth in mice was blocked by miR-490-3p upregulation. MiR-490-3p suppressed bladder cancer growth and bladder cancer cell proliferation by down-regulating PCBP2 expression.

The Expression and Regulation of Na+-K+-ATPase in Nasal Epithelial Cells of Chronic Rhinosinusitis with Nasal Polyps.

OBJECTIVE: Na+-K+-ATPase (NKA) is essential in maintaining cell permeability, reserving potential energy, and preventing cellular edema. Nevertheless, how NKA expression is altered and regulated in chronic rhinosinusitis with nasal polyps (CRSwNPs) remain uncertain. Therefore, the present study aimed to explore the expression and regulation of NKA in CRSwNP. METHODS: NKA immunolabeling was assessed by the immunohistochemistry method, NKA protein levels were detected with the Western blotting method, and mRNA levels of NKA and aquaporin-5 (AQP5) were assayed by real-time PCR in nasal tissues from CRSwNP and control subjects. The co-localization of NKA with inflammatory cells was evaluated by immunofluorescence staining. In addition, human nasal epithelial cells (HNECs) were cultured and stimulated using various stimulators to evaluate the regulation of NKA. RESULTS: We found significantly decreased NKA positive cells, NKA protein levels, and mRNA levels of NKA and AQP5 in nasal tissues from CRSwNP patients compared to control subjects, especially in eosinophilic CRSwNP. Furthermore, NKA mRNA levels in HNECs were downregulated by staphylococcal enterotoxin B (SEB), lipopolysaccharides (LPSs), inflammatory cytokine (IFN)-γ, IL-4, IL-13, and IL-1ß. CONCLUSION: NKA and AQP5 expressions were decreased in CRSwNP. NKA in HNECs could be suppressed by SEB, LPS, IFN-γ, IL-4, IL-13, and IL-1ß. Impairment of NKA may contribute to the genesis and development of CRSwNP via inducing AQP5 downregulation and edema.

Effect of Dexmedetomidine on Tachyarrhythmias After Cardiac Surgery: A Systematic Review and Meta-Analysis.

ABSTRACT: Tachyarrhythmias after cardiac surgery is a common occurrence in clinical practice, which can be life threatening. We searched 6 databases, including Embase, PubMed, Cochrane, CNKI, Wanfang, and Sinomed, to evaluate the effect of dexmedetomidine on tachyarrhythmias after adult cardiac surgery. The primary end point was the number of patients with atrial fibrillation (AF) after cardiac surgery. The secondary end points included the number of patients with supraventricular tachycardia or with ventricular tachycardia or with ventricular fibrillation or with myocardial infarction or deceased patients, the duration of mechanical ventilation, the intensive care unit stay, hospital stay, and the number of patients with bradycardia and those with hypotension. Among the 1388 retrieved studies, 18 studies (n = 3171 participants) met our inclusion criteria. Dexmedetomidine reduced the incidence of AF by 17% [relative risk (RR) = 0.83; 95% confidence interval (CI), 0.73-0.93; P = 0.002]. Through subgroup analysis, we found that when the maintenance dose of dexmedetomidine was >0.7 µg·kg-1·h-1, the effect of preventing AF was obvious (RR = 0.58; 95%CI 0.43-0.78; P = 0.0003). Dexmedetomidine also reduced the incidence of supraventricular tachycardia by approximately 70% (RR = 0.29; 95% CI, 0.11-0.77; P = 0.01) and the incidence of ventricular tachycardia by approximately 80% (RR = 0.23; 95% CI, 0.08-0.63; P = 0.004) but had no effect on ventricular fibrillation (RR = 1.02; 95% CI, 0.14-7.31; P = 0.99). The major side effect of dexmedetomidine was bradycardia. Dexmedetomidine can reduce the incidence of AF (especially high dosages), supraventricular tachycardia, and ventricular tachycardia after cardiac surgery in adults, but it does not affect the occurrence of ventricular fibrillation.

Effect of single-port inflatable mediastinoscopy simultaneous laparoscopic-assisted radical esophagectomy on respiration and circulation.

BACKGROUND AND PURPOSE: We previously developed a new surgical method, namely, single-port inflatable mediastinoscopy simultaneous laparoscopic-assisted radical esophagectomy. The purpose of this study was to evaluate the effect of carbon dioxide inflation on respiration and circulation using this approach. METHODS: From April 2018 to October 2020, 105 patients underwent this novel surgical approach. The changes in respiratory and circulatory functions were reported when the mediastinal pressure and pneumoperitoneum pressure were 10 and 12 mmHg, respectively. Data on blood loss, operative time, and postoperative complications were also collected. RESULTS: 104 patients completed the operation successfully, except for 1 patient who was converted to thoracotomy because of intraoperative injury. During the operation, respectively, the heart rate, mean arterial pressure, central venous pressure, peak airway pressure, end-expiratory partial pressure of carbon dioxide and partial pressure of carbon dioxide increased in an admissibility range. The pH and oxygenation index decreased 1 h after inflation, but these values were all within a safe and acceptable range and restored to the baseline level after CO2 elimination. Postoperative complications included anastomotic fistula (8.6%), pleural effusion that needed to be treated (8.6%), chylothorax (0.9%), pneumonia (7.6%), arrhythmia (3.8%) and postoperative hoarseness (18.2%). There were no cases of perioperative death. CONCLUSIONS: When the inflation pressure in the mediastinum and abdomen was 10 mmHg and 12 mmHg, respectively, the inflation of carbon dioxide from single-port inflatable mediastinoscopy simultaneous laparoscopic-assisted radical esophagectomy did not cause serious changes in respiratory and circulatory function or increase perioperative complications.

Broadening the Spectral Response of Perovskite Photodetector to the Solar-Blind Ultraviolet Region through Phosphor Encapsulation.

Hybrid perovskite photodetectors generally exhibit brilliant performance for photodetecting in the visible spectrum but poor detectability in the solar-blind ultraviolet (UV) region. To break through the bottleneck, we demonstrate a novel strategy to broaden the spectral response of perovskite photodetectors to the solar-blind UV region through phosphor encapsulation. The high photoluminescence quantum yield trichromatic phosphor capping layer achieves an extended spectral response to the solar-blind UV region through effectively down-converting the incident UV light into visible light. In addition, an external quantum efficiency of up to 12.13%@265 nm is achieved without bias voltage, while the initial value is near zero. The corresponding spectral responsivity and detectivity are 0.0269 A/W and 7.52 × 1011 Jones, respectively. Thus, the photodetectors show a high photocurrent and on/off ratio, increasing by roughly 2 orders of magnitude. Moreover, the photodetectors exhibit a large linear dynamic range of 105 dB, fast response times of 50.16/51.99 µs, and excellent stability. The practical applications for flame detection and UV-based communication are further explored. This work provides a new way to achieve UV light detection based on perovskite photodetectors. Perhaps, it may also be a promising alternative for wide-band gap semiconductors to realize the urgent pursuit of UV detection.

Ultrafast, Self-Powered, and Charge-Transport-Layer-Free Ultraviolet Photodetectors Based on Sequentially Vacuum-Evaporated Lead-Free Cs2AgBiBr6 Thin Films.

Researchers have focused on perovskite-based ultraviolet photodetectors due to their significance in fundamental scientific and practical applications. However, toxicity and instability hold back their mass production and commercialization. The lead-free Cs2AgBiBr6 double perovskite, promised to be an alternative, is fabricated mostly by spin coating, which restricts the practical application in high-resolution image sensors. Herein, we demonstrate a sequential vacuum evaporation method for the fabrication of the Cs2AgBiBr6 film. A self-powered ultraviolet photodetector based on the evaporated Cs2AgBiBr6 thin film is further constructed without any carrier-transport layers, for the first time. The best-performing device has a high on/off ratio of 6.6 × 103, and its response time is fast, less than 6.13 µs. Moreover, the as-prepared devices exhibit salient stability under harsh operational conditions (continuous illumination, high temperature, and humidity). In addition, the pixelated image sensor containing a 25 × 25 Cs2AgBiBr6 photodetector array achieves a proof-of-concept special pattern recognition. Our work paves the way for new-generation ultraviolet image sensors composed of environmentally friendly and high-performance perovskite photodetector arrays.

Evidence for role of acid-sensing ion channel 1a in chronic rhinosinusitis with nasal polyps.

PURPOSE: A variety of inflammatory cells are infiltrated histologically in sinonasal mucosa of chronic rhinosinusitis with nasal polyps (CRSwNP), especially CRSwNP with asthma. Acid-sensing ion channel 1a (ASIC1a) is essential in the process of sensing acidification and triggering inflammation. Whereas, its role and mechanism in CRSwNP remain uncertain. The present study aimed to explore the roles and mechanism of ASIC1a in the pathogenesis of CRSwNP. METHODS: Nasal secretions from control subjects, patients with CRSwNP with or without asthma were collected for measuring pH values. Western blotting, real-time PCR and immunohistochemistry (IHC) were employed to assess ASIC1a expression in nasal tissue samples from included subjects. The co-localization of ASIC1a with inflammatory cells was evaluated by immunofluorescence staining. Then, dispersed nasal polyp cells (DNPCs) were cultured under acidified condition (pH 6.0), with or without ASIC1a inhibitor amiloride. Western blotting, real-time PCR, LDH activity kit, and ELISA were performed to assess the effects and mechanisms of stimulators on the cells. RESULTS: The pH values were significantly lower in the nasal secretions from patients with CRSwNP with asthma. Significant upregulation of ASIC1a protein, mRNA levels, and positive cells was found in CRSwNP with asthma. ASIC1a was detected in a variety of inflammatory cells. In cultured DNPCs, significant alterations of ASIC1a levels, LDH activity, HIF-1α levels, and inflammatory cytokines were found under acidified condition (pH 6.0), but were prevented by amiloride. CONCLUSION: Upregulation of ASIC1a might be essential in the process of sensing acidification and triggering inflammatory response via enhancing HIF-1α expression and LDH activity to activate inflammatory cells in the pathogenesis of CRSwNP, especially in CRSwNP with asthma.

Increased Expression of TXNIP Facilitates Oxidative Stress in Nasal Epithelial Cells of Patients With Chronic Rhinosinusitis With Nasal Polyps.

BACKGROUND: Oxidative stress plays crucial roles in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Thioredoxin-interacting protein (TXNIP) is essential in the process of triggering oxidative stress. However, its role and mechanism in CRSwNP remain unclear. The present study sought to explore the role and mechanism of TXNIP in the pathogenesis of CRSwNP. METHODS: Western blotting, real-time PCR and immunohistochemistry (IHC) were employed to assess TXNIP, thioredoxin (TRX) expression in nasal tissue samples from patients with CRSwNP and control subjects. MDA level and SOD activity in nasal tissue homogenates were measured using MDA and SOD Assay Kit. To evaluate the role and mechanism of TXNIP in CRSwNP, human nasal epithelial cells (HNECs) were cultured and stimulated using TXNIP siRNA, with or without N-acetylcysteine (NAC, an ROS scavenger). Western blotting, real-time PCR, ROS detecting dye DCFH-DA, MDA and SOD Assay Kit were performed to assess the effects and mechanisms of stimulators on the cells. RESULTS: We found significantly increased levels of TXNIP and decreased levels of TRX protein, mRNA, positive cells, increased MDA level and decreased SOD activity in CRSwNP patients compared with control subjects. In vitro study, significantly altered levels of TXNIP, TRX, MDA, SOD and ROS in HNECs were found following treatment of TXNIP siRNA with or without NAC on HNECs. CONCLUSION: TXNIP expression was increased and TRX expression was decreased in CRSwNP at both protein and mRNA levels. MDA levels were increased and SOD activities were decreased in CRSwNP. TXNIP may have negative association with TRX, and then decrease SOD activities and increase MDA levels, resulting in the upregulation of ROS and oxidative stress in HNECs, which may play a pivotal role in the pathogenesis of CRSwNP. Future studies are expected to further explore the role and mechanism of TXNIP in CRSwNP.

Treatment and Outcomes of Iatrogenic Cerebrospinal Fluid Leak Caused by Different Surgical Procedures.

BACKGROUND: Iatrogenic cerebrospinal fluid (CSF) leaks are associated with serious sequelae. We analyzed the causes, complications, treatments, and outcomes of iatrogenic CSF leaks. Furthermore, the comorbidities and outcomes between timely and delayed repairs of iatrogenic CSF leaks were also compared. METHODS: Medical records of patients with iatrogenic CSF leaks from January 2010 to January 2020 were reviewed. RESULTS: Iatrogenic CSF leaks can be attributed to endoscopic sinus surgery (ESS), transsphenoidal pituitary surgery, open craniotomy, or postradiation necrosis. Twenty-nine patients diagnosed with iatrogenic CSF leak were recruited. The primary diagnoses included 12 (41.4%) nasal lesions, 7 (24.2%) pituitary tumors, 3 (10.3%) anterior cranial fossa lesions, 4 (13.8%) cerebellopontine angle lesions, and 3 (10.3%) clival lesions. The longest interval from symptom onset to presentation at our hospital was observed after craniotomy, followed by transsphenoidal surgery and ESS, increasing the risks of meningitis in these patients. The most common leakage sites after ESS and transsphenoidal surgery were the cribriform plate/ethmoid roof and sella turcica, respectively, whereas the defect sites related to open craniotomy varied. The grafts used for repair varied according to the defect location and prior surgical history. Additionally, patients in whom repair was delayed had a higher incidence of meningitis (P = 0.003), than those with timely repair. CONCLUSIONS: Delayed intervention of CSF leak after transsphenoidal surgery and craniotomy was observed, increasing the risks of meningitis. Timely intervention with grafts based on the defect sites and patient prior surgical history is crucial for avoiding life-threatening comorbidities.

Contrast-Enhanced MRI Combined With the Glycerol Test Reveals the Heterogeneous Dynamics of Endolymphatic Hydrops in Patients With Menière's Disease.

BACKGROUND: The sensitivity of endolymphatic hydrops (EH) to the glycerol test varies in patients with Menière's disease (MD). PURPOSE: To explore the features of EH and its glycerol-induced dynamics in MD. STUDY TYPE: Case-control study. POPULATION: Twenty patients with MD (24 affected ears) were included. FIELD STRENGTH/SEQUENCE: 3.0T 3D-FLAIR (fluid-attenuated inversion recovery) MRI and late gadolinium enhancement. ASSESSMENT: Intratympanic gadolinium-enhanced MRI was performed in the MD-affected ears before and after the glycerol test. The borders of the endolymphatic and total lymphatic space were contoured on the axial MRI slices to evaluate the volume of hydrops in both the cochlear and vestibular regions. STATISTICAL TESTS: Paired and unpaired t-tests, the Mann-Whitney U-test, linear discriminant analysis, Pearson's correlation, and linear regression. RESULTS: After glycerol ingestion, vestibular EH decreased in all patients, whereas cochlear EH significantly decreased only in patients with positive glycerol test results (all P < 0.01). At baseline, cochlear EH in the positive result group was greater than in the negative result group (P = 0.007). Unexpectedly, in the positive result group a drastic glycerol-induced dehydrating effect was observed in patients whose pretest cochlear EH ratio was >16% (P = 0.011). Moreover, the dehydrating role of glycerol was positively correlated with the baseline cochlear hydrops level (r = 0.7691, P < 0.001). DATA CONCLUSION: MRI provides evidence that glycerol administration improves the hearing threshold via dehydrating the EH. In the cochlear region, the baseline level of cochlear EH is a closely related factor for the validity of the glycerol test, whereas EH is consistently dehydrated in the vestibular component. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3 J. Magn. Reson. Imaging 2020;52:1066-1073.

Surgical Treatment and Outcomes for Sinonasal and Skull Base Phosphaturic Mesenchymal Tumors.

OBJECTIVE: To describe our clinical experience with surgical treatments for sinonasal phosphaturic mesenchymal tumors diagnosed at our institution. STUDY DESIGN: Retrospective case series. SETTING: Affiliated Sixth People's Hospital, Shanghai Jiao Tong University. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of 10 patients diagnosed with phosphaturic mesenchymal tumors associated with tumor-induced osteomalacia between December 2014 and October 2019. RESULTS: There were 4 men and 6 women with a disease course of 1 to 19 years. All patients exhibited hypophosphatemia and tumor-induced osteomalacia. The tumor was located in the sinonasal region, frontal bone, and temporal bone in 8 patients, 1 patient, and 1 patient, respectively. Technetium-99m octreotide scintigraphy was used for tumor localization in 4 cases. Six patients underwent endoscopic resection; the remaining 4 underwent unilateral transorbital anterior and posterior ethmoid artery ligation + endoscopic resection, endoscopic resection + skull base repair, internal carotid artery stenting + transcatheter arterial embolization + temporal bone tumor excision + adipose tissue plugging, and endoscopic resection + transfrontal craniotomy (n = 1 each). Two patients had a history of incomplete endoscopic resection. All patients achieved clinical remission and normalized biochemical indices after surgery. Only 1 patient developed recurrence and died of a brain hernia. CONCLUSIONS: A diagnosis of sinonasal phosphaturic mesenchymal tumors should be based on a combination of clinical, imaging, and pathological findings. Technetium-99m octreotide scintigraphy helps in locating the tumor. Complete surgical excision guarantees clinical remission, and preoperative transcatheter arterial embolization or feeding artery ligation may reduce intraoperative bleeding in cases of highly vascularized tumors.

Radiofrequency Coblation-Assisted Resection of Skull Base Neoplasms Using an Endoscopic Endonasal Approach.

OBJECTIVES: We describe our early experiences with resecting skull base tumors using a radiofrequency ablation-assisted endoscopic endonasal approach. Ninety-seven patients with skull base tumors who were admitted to the Otorhinolaryngology department at Shanghai Jiaotong University Affiliated Shanghai Sixth People's Hospital between January 2014 and December 2016 were operated on using a radiofrequency ablation-assisted endoscopic endonasal approach. Complete resection was achieved in all patients. This paper describes the operative technique and presents the degree of resection, complications, and early clinical outcomes. METHODS: We investigated the safety and feasibility of the technique and assessed preliminary treatment outcomes. RESULTS: No patients experienced a new neurological deficit, cerebrospinal fluid leak, or meningitis after surgery. No deaths related to skull base tumors were observed during the follow-up period (14-50 months). The volume of intraoperative blood loss was 100-1,200 mL (median 350 mL), the duration of operation was 40-510 min (median 180 min), and the hospital stay was 6-65 days (median 18). CONCLUSIONS: Our limited experience indicates that this technique is feasible and safe for complete resection of some skull base tumors in selected cases and in the future will have an increasing role to play in endoscopic sinonasal and skull base tumor dissection.

Cytochrome P450 1A2 Is Incapable of Oxidizing Bilirubin Under Physiological Conditions.

Background: Bilirubin (BR) is metabolized mainly by uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) through glucuronidation in the liver. Some studies have shown that several subtypes of cytochrome P450 (CYP) enzymes, including CYP1A2, are upregulated by inducers and proposed to be alternative BR degradation enzymes. However, no information is available on the BR degradation ability of CYP in normal rats without manipulation by CYP inducers. Methods: Quantitative real-time polymerase chain reaction (QRT-PCR), western blot, immunofluorescence, and confocal microscopy were used to find expression of CYP1A2 in the brain and the liver. BR metabolites in microsomal fractions during development were examined by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC-MS/MS). Results: In the present study, we observed that CYP1A2 mRNA levels increased at postnatal days (P)14 and P30 with respect to the level at P7 both in liver and brain, this increment was especially pronounced in the brain at P14. The expression of CYP1A2 in the brainstem (BS) was higher than that in the cerebellum (CLL) and cortex (COR). Meanwhile, the CYP1A2 protein level was significantly higher in the COR than in the brainstem and CLL at P14. The levels of BR and its metabolites (m/z values 301, 315, 333 and biliverdin) were statistically unaltered by incubation with liver and brain microsomal fractions. Conclusion: Our results indicated that the region-specific expression of CYP1A2 increased during development, but CYP family enzymes were physiologically incapable of metabolizing BR. The ability of CYPs to oxidize BR may be triggered by CYP inducers.

Ca2+-dependent recruitment of voltage-gated sodium channels underlies bilirubin-induced overexcitation and neurotoxicity.

Neonatal jaundice is prevalent among newborns and can lead to severe neurological deficits, particularly sensorimotor dysfunction. Previous studies have shown that bilirubin (BIL) enhances the intrinsic excitability of central neurons and this can potentially contribute to their overexcitation, Ca2+ overload, and neurotoxicity. However, the cellular mechanisms underlying elevated neuronal excitability remain unknown. By performing patch-clamp recordings from neonatal neurons in the rat medial vestibular nucleus (MVN), a crucial relay station for locomotor and balance control, we found that BIL (3 µM) drastically increases the spontaneous firing rates by upregulating the current-mediated voltage-gated sodium channels (VGSCs), while shifting their voltage-dependent activation toward more hyperpolarized potentials. Immunofluorescence labeling and western immunoblotting with an anti-NaV1.1 antibody, revealed that BIL elevates the expression of VGSCs by promoting their recruitment to the membrane. Furthermore, we found that this VGSC-trafficking process is Ca2+ dependent because preloading MVN neurons with the Ca2+ buffer BAPTA-AM, or exocytosis inhibitor TAT-NSF700, prevents the effects of BIL, indicating the upregulated activity and density of functional VGSCs as the core mechanism accountable for the BIL-induced overexcitation of neonatal neurons. Most importantly, rectification of such overexcitation with a low dose of VGSC blocker lidocaine significantly attenuates BIL-induced cell death. We suggest that this enhancement of VGSC currents directly contributes to the vulnerability of neonatal brain to hyperbilirubinemia, implicating the activity and trafficking of NaV1.1 channels as a potential target for neuroprotection in cases of severe jaundice.