Surgical Management of Complex Skull Base Tumor Using Preoperative Multimodal Image Fusion Technology.

OBJECTIVE: To review our single-institution experience in the surgical management of complex skull base tumors using multimodal image fusion technology. METHODS: From October 2019 to January 2022, 7 cases of complex skull base tumors that performed preoperative multimodal image fusion in Zhuhai People's Hospital neurosurgery department were involved in this study. The image data were uploaded to the GE AW workstation. Corresponding image sequences were opened in the workstation to complete registration fusion and 3D reconstruction. We retrospectively reviewed the clinical and imaging data, and surgical strategy, respectively. RESULTS: one case of recurrent C2 schwannoma, 1 case of recurrent spindle cell tumor of the left cranio-orbital communication, 1 case of lobular malignant tumor of the left infratemporal fossa, 1 case of central giant cell repairing granuloma, 1 case of mesenchymal malignant tumor in left pharyngeal process, 1 case of meningioma in jugular foramen, and 1 case of hemangioblastoma with vascular malformation in fourth ventricular. All cases underwent preoperative multimodal image fusion for the surgical plan and all cases had gross total resection. Except for one case of mesenchymal malignant tumor in left pharyngeal process that had dysphagia and one case of hemangioblastoma that had discoordination, others cases were without postoperative complication. CONCLUSIONS: Preoperative multimodal image fusion and surgical approach simulation benefit complex skull base tumor surgical treatment. Individually multiple image assessment of complex skull base tumors to determine the specific surgical strategy is more rational and should be recommended (Supplemental Digital Content 1, Supplementary Video, http://links.lww.com/SCS/F936).

Correlation between vascular endothelial growth factor A gene polymorphisms and tendon and ligament injury risk: a systematic review and meta-analysis.

BACKGROUND: Relevant evidence suggests that angiogenic factors contribute significantly to fibril matrix reconstruction following physical injuries to tendon ligaments. Vascular endothelial growth factor A (VEGFA), with its potent angiogenic effect, has been studied extensively, and its functional polymorphisms, including rs699947, rs1570360, and rs2010963, have been the focus of numerous investigations. Some scholars have explored the association between gene polymorphisms in the VEGFA and the risk of tendon ligament injury, but the findings are not entirely consistent. OBJECTIVES: The purpose of this study was to investigate the association between rs699947, rs1570360, and rs2010963 gene polymorphisms in VEGFA and the risk of tendon and ligament injuries. METHODS: After including articles about the association of VEGFA rs699947, rs1570360, and rs2010963 polymorphisms with tendon and ligament injuries according to the search strategy, we assessed their quality and conducted meta-analyses to examine the link between these polymorphisms and the risk of tendon and ligament injuries using odds ratios and 95% confidence intervals. RESULTS: Of 86 related articles, six were included in the meta-analysis. Some of these suggest an association between VEGFA rs2010963 and the risk of tendon and ligament injury in the population, with the specific C allele being one of the adverse factors for knee injury. Some studies suggest that VEGFA rs699947 and VEGFA rs1570360 single-nucleotide polymorphisms are associated with anterior cruciate ligament rupture. The risk of non-contact anterior cruciate ligament rupture is nearly doubled in individuals with the rs699947 CC genotype compared to the control group. Our analysis did not find any significant relationship between VEGFA gene polymorphisms (rs699947, rs1570360, and rs2010963) and the chance of tendon and ligament injury without consideration of race. However, the European population reveals that the CC genotype of VEGFA rs699947 can result in a greater risk of tendon and ligament injury, whereas the AG genotype for rs1570360 provides some protection. Additionally, rs2010963 was significantly associated with tendon and ligament injury; individuals with the C allele and the CC genotype had higher risk. False-positive report probability confirmed the high credibility of our results. CONCLUSION: Overall, this study found no significant association between VEGFA rs699947, rs1570360, and rs2010963 polymorphisms and the risk of tendon ligament injury. However, in subgroup analysis, some genotypes of VEGFA rs699947, rs1570360, and rs2010963 were found to increase the risk of tendon ligament injury in European populations.

Synthesis of Imidazo[1,2-a]pyridine-Fused 1,3-Benzodiazepine Derivatives with Anticancer Activity via a One-Pot Cascade GBB-3CR/Pd(II)-Catalyzed Azide-Isocyanide Coupling/Cyclization Process.

A new one-pot synthesis of imidazo[1,2-a]pyridine-fused 1,3-benzodiazepine derivatives via a sequential GBB-3CR/Pd(II)-catalyzed azide-isocyanide coupling/cyclization process was developed. The Groebke-Blackburn-Bienaymé three-component reactions (GBB-3CR) of 2-aminopyridine, 2-azidobenzaldehydes, and isocyanides in the presence of a catalytic amount of p-toluenesulfonic acid gave azide intermediates without separation. The reaction was followed by using another molecule of isocyanides to produce imidazo[1,2-a]pyridine-fused 1,3-benzodiazepine derivatives in good yields by the Pd(II)-catalyzed azide-isocyanide coupling/cyclization reaction. The synthetic approach produces novel nitrogen-fused polycyclic heterocycles under mild reaction conditions. The preliminary biological evaluation demonstrated that compound 6a inhibited glioma cells efficiently, suggesting potentially broad applications of the approach for synthesis and medicinal chemistry.

Efficacy of oblique lumbar interbody fusion versus transforaminal lumbar interbody fusion in the treatment of lumbar degenerative diseases: a systematic review and meta-analysis.

INTRODUCTION: This meta-analysis aimed to compare the differences in postoperative efficacy between oblique lumbar interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in the treatment of lumbar degenerative diseases. MATERIALS AND METHODS: Strictly based on the search strategy, we searched the published papers on OLIF and TLIF for the treatment of lumbar degenerative diseases in PubMed, Embase, CINAHL, and Cochrane Library. A total of 607 related papers were retrieved, and 15 articles were finally included. The quality of the papers was evaluated according to the Cochrane systematic review methodology, and the data were extracted and meta-analyzed using Review manager 5.4 software. RESULTS: Through comparison, it was found that in the treatment of lumbar degenerative diseases, the OLIF group had certain advantages over the TLIF group in terms of intraoperative blood loss, hospital stay, visual analog scale (VAS) for leg pain (VAS-LP), Oswestry disability index (ODI), disc height (DH), foraminal height (FH), fused segmental lordosis (FSL), and cage height, and the differences were statistically significant. The results were similar in terms of surgery time, complications, fusion rate, VAS for back pain (VAS-BP) and various sagittal imaging indicators, and there was no significant difference. CONCLUSIONS: OLIF and TLIF can relieve low back pain symptoms in the treatment of lumbar degenerative diseases, but OLIF has certain advantages in terms of ODI and VAS-LP. In addition, OLIF has the advantages of minor intraoperative trauma and quick postoperative recovery.

Application of Preoperative Multimodal Image Fusion Technique in Microvascular Decompression Surgery via Suboccipital Retrosigmoid Approach.

OBJECTIVE: To explore the application value of preoperative multimodal image fusion technique in microvascular decompression (MVD) surgery via the suboccipital retrosigmoid approach. METHODS: Comprehensive data of 13 patients with primary trigeminal neuralgia (TN) and 13 patients with hemifacial spasm (HFS) treated by MVD surgery via the suboccipital retrosigmoid approach at the Department of Neurosurgery in Zhuhai People's Hospital from January 2021 to December 2021 were retrospectively analyzed. Preoperatively, all patients underwent cranial thin-section computed tomography and magnetic resonance examinations. Three-dimensional (3D) digital images of the skull, brainstem, nerves, and blood vessels were constructed by the 3D-slicer software or RadiAnt DICOM Viewer, which were then applied to design the surgical approach and surgical plan. The multimodal image fusion results, clinical characteristics, intraoperative data, surgical outcomes, and complications of all patients were summarized. RESULTS: The 3D digital images after fusion reconstruction can vividly show the anatomical relationship between the skull, brainstem, nerves, and blood vessels and was helpful to tailor the surgical strategy. All 26 patients underwent a smooth surgery. During the surgery, the key points were accurately located, the corners of the transverse sinus and sigmoid sinus were completely exposed, and no venous sinus injury occurred in all 26 patients. The key point was approximately located at the top point of the digastric groove, 12.3 ± 0.46 mm vertically above and 6.3 ± 0.6 mm laterally to the Frankfurt horizontal plane. The average cranial opening time was 30.4 (±3.6) min, and the mean operating time was 104.7 (±12.1) min. The diameter of the bone window was about 2.0 cm-3.0 cm, and the bone flap was restored. Among the 13 patients with primary TN, 12 (92.3%) exhibited complete relief of pain and 1 had significant relief. Complications of surgery included facial sensory numbness in 1 case, vertigo in 2 cases, and herpes at the corners of the mouth in 1 case. Of the 13 patients with HFS, 12 (92.3%) had complete relief of facial twitching symptoms and 1 had significant relief, and the complications included mild facial palsy in 2 (15.4%) cases and facial sensory numbness in another 2 (15.4%) cases. The mean follow-up time after surgery ranged from 6-16 months, and 1 of 26 patients experienced recurrence of HFS during the follow-up period. CONCLUSIONS: Preoperative multimodal image fusion technology can provide adequate preoperative assessment for patients and assistance in designing surgical approaches, which is an important guideline for MVD surgery via the suboccipital retrosigmoid approach for primary TN and facial muscle spasm.

Loss of selenoprotein W in murine macrophages alters the hierarchy of selenoprotein expression, redox tone, and mitochondrial functions during inflammation.

Macrophages play a pivotal role in mediating inflammation and subsequent resolution of inflammation. The availability of selenium as a micronutrient and the subsequent biosynthesis of selenoproteins, containing the 21st amino acid selenocysteine (Sec), are important for the physiological functions of macrophages. Selenoproteins regulate the redox tone in macrophages during inflammation, the early onset of which involves oxidative burst of reactive oxygen and nitrogen species. SELENOW is a highly expressed selenoprotein in bone marrow-derived macrophages (BMDMs). Beyond its described general role as a thiol and peroxide reductase and as an interacting partner for 14-3-3 proteins, its cellular functions, particularly in macrophages, remain largely unknown. In this study, we utilized Selenow knock-out (KO) murine bone marrow-derived macrophages (BMDMs) to address the role of SELENOW in inflammation following stimulation with bacterial endotoxin lipopolysaccharide (LPS). RNAseq-based temporal analyses of expression of selenoproteins and the Sec incorporation machinery genes suggested no major differences in the selenium utilization pathway in the Selenow KO BMDMs compared to their wild-type counterparts. However, selective enrichment of oxidative stress-related selenoproteins and increased ROS in Selenow-/- BMDMs indicated anomalies in redox homeostasis associated with hierarchical expression of selenoproteins. Selenow-/- BMDMs also exhibited reduced expression of arginase-1, a key enzyme associated with anti-inflammatory (M2) phenotype necessary to resolve inflammation, along with a significant decrease in efferocytosis of neutrophils that triggers pathways of resolution. Parallel targeted metabolomics analysis also confirmed an impairment in arginine metabolism in Selenow-/- BMDMs. Furthermore, Selenow-/- BMDMs lacked the ability to enhance characteristic glycolytic metabolism during inflammation. Instead, these macrophages atypically relied on oxidative phosphorylation for energy production when glucose was used as an energy source. These findings suggest that SELENOW expression in macrophages may have important implications on cellular redox processes and bioenergetics during inflammation and its resolution.

Combination of Preoperative Multimodal Image Fusion and Intraoperative Dyna CT in Percutaneous Balloon Compression of Trigeminal Ganglion for Primary Trigeminal Neuralgia: Experience in 24 Patients.

Objective: We retrospectively assessed the surgical results of PBC with preoperative multimodal image fusion and intraoperative Dyna Computed Tomography (CT) in 24 patients with primary trigeminal neuralgia (PTN) to explore a valuable aid for Percutaneous balloon compression (PBC). Methods: We studied the data of 24 patients with PTN. All patients underwent PBC and were assessed with preoperative multimodal image fusion [computed tomography (CT) and magnetic resonance imaging (MRI)] and intraoperative Dyna CT in the Department of Neurosurgery of Zhuhai People's Hospital between October 2020 and September 2021. Multimodal image fusion-three-dimensional (3D) reconstruction of CT and MRI data-was performed using 3D-Slicer software, and preoperative evaluation was performed according to the results of image fusion. Dyna CT was used to dynamically observe the position and shape of the metallic hollow introducer and Fogarty catheter and balloon during the operation to guide the operation in real time. We performed follow-up assessments each month and summarized the clinical characteristics, surgical effects, and complications in all patients. Results: Surgery was successful for all patients; the patients reported immediate pain relief. Surgical complications included facial numbness in 24 patients (100%), mild masseter weakness in three (12.5%), herpes zoster in three (12.5%), and balloon rupture in one (4.2%). None of the patients had serious surgical complications. The mean follow-up time was 9.6 ± 2.7 months. During the follow-up period, 22 patients (91.7%) experienced no recurrence of pain, and two patients (8.3%) experienced recurrence of pain, of which one underwent secondary PBC surgery. Conclusions: Preoperative multimodal image reconstruction can help fully evaluate PBC surgery, clarify the etiology, and predict the volume of contrast medium required during the operation. It provided important assistance for PBC treatment of trigeminal neuralgia patients when preoperative multimodal image fusion is combined with intraoperative Dyna CT.

Thymoma-Related Paraneoplastic Syndrome Mimicking Reactive Arthritis.

Background and Objectives: Thymomas are associated with a high frequency of paraneoplastic manifestations. Paraneoplastic syndrome (PNS) with thymoma presents a challenge to clinicians because of the need to decipher the association between the presenting symptoms and the underlying tumor. The condition most commonly noted in patients with PNS with thymoma is myasthenia gravis. Other common autoimmune diseases that may present as PNS include systemic lupus erythematosus, pure red cell aplasia, and Good syndrome. Seventy-six percent of patients with PNS-associated thymoma experience resolution of PNS after curing thymoma. Materials and Methods: A 37-year-old man with a two-month fever accompanied by polyarthritis accidently found thymoma after contrast computed tomography scans of his chest. He accepted Video assisted thoracoscopic surgery with resection of thymoma. Results: Fever and polyarthritis resolved after operation but recurred in five days due to cytomegalovirus viremia, which might be predisposed by previous antibiotics treatment before the diagnosis of thymoma. Conclusion: Patients with a thymoma also have a high frequency of PNS, and the most frequent condition found in patients with PNS-associated thymoma is myasthenia gravis. Fever with polyarthritis has been rarely reported as a symptom of PNS-associated thymoma. Here we reported an unusual case of PNS mimicking reactive arthritis with thymoma, as diagnosed based on the patient's clinical progression, imaging examination, and laboratory tests. The patient died of his comorbidities, and his death may have been related to long-term antibiotic use and consequent intestinal dysbiosis. This challenging case may help to inform clinicians of the need for detailed work-up of fever with unknown origin in the presence of chronic polyarthritis to prevent the overdiagnosis of inflammatory arthritis or rheumatic disease and avoid further comorbidities. Detailed work-up should include the patient's history of infections, inflammation, and malignant or nonmalignant tumors.

NIX protein enhances antioxidant capacity of and reduces the apoptosis induced by HSP90 inhibitor luminespib/NVP-AUY922 in PC12 cells.

Pheochromocytomas and paragangliomas (PCPGs) are catecholamine-producing neuroendocrine tumors. Accumulating evidences indicate that the blockade of antioxidative pathways might be a novel therapeutic approach to the treatment of PCPG. NIX has been confirmed to play a key role in maintaining redox homeostasis in tumors, while the function of NIX in PCPG remains unclear. In this study, the analyses of the disease-free survival (DFS) showed that high NIX protein level is related to poor prognosis in patients of PCPG. Consistent with this, high level of NIX protein upregulates the level of p-NF-κB and promotes the migration of PC12 cells. In NIX-over-expressing PC12 cells, the level of reactive oxygen species (ROS) is decreased while trolox-equivalent antioxidant capacity (TEAC) increased. But in NIX-silencing cells, ROS level is increased, while TEAC reversely reduced, consequently antioxidase and phase II enzymes of NRF2 signaling were activated, and elevated endoplasmic reticulum (ER) stress was observed. Additionally, the apoptosis induced by luminespib/NVP-AUY922, an inhibitor of heat shock protein 90 (HSP90, a cellular stress response factor), was enhanced in NIX-silencing cells but reduced in the NIX-over-expressing cells. All of these results indicated that high NIX protein level enhances antioxidant capacity of PC12 cells and reduces the apoptosis caused by cell stress, such as induced by luminespib/NVP-AUY922. Therefore, luminespib/NVP-AUY922 might be effective only for PCPG with low NIX level, while targeting NIX could be a further supplement to the therapeutic treatment strategy for PCPG patients with high NIX protein level.

cIAP2 via NF-κB signalling affects cell proliferation and invasion in hepatocellular carcinoma.

AIMS: To investigate the role of cIAP2 in the malignant biological behaviours of hepatocellular carcinoma (HCC) cells and determine its mechanism of action. MAIN METHODS: cIAP2 protein expression was detected via immunohistochemistry (IHC) in 102 HCC specimens and 43 paracancerous liver tissues, and its relationship with clinicopathological features and patient prognosis was analysed. Then, short interfering RNA (siRNA) technology was used to knock down cIAP2 expression in BEL7402 and HepG2 cells. Cell Counting Kit-8 (CCK8) and Transwell assays were used to determine cell proliferation and invasion after knockdown of cIAP2 expression. The relationship between cIAP2 and the NF-κB pathway was explored via western blotting (WB) and a dual luciferase reporter system. Finally, nude mouse models of liver cancer were established to detect the effect of cIAP2 on tumourigenicity and the proliferation activity of orthotopic HCC cells. KEY FINDINGS: cIAP2 expression was significantly increased in HCC tissues and was correlated with intravascular thrombosis in HCC. High cIAP2 expression was correlated with poor patient prognosis. cIAP2 knockdown significantly reduced the proliferation and invasion of BEL7402 and HepG2 cells and the activity of the NF-κB pathway. Animal experiments showed that cIAP2 knockdown reduced the tumourigenicity of HepG2 cells in the liver of nude mice and the proliferation activity of the orthotopic HCC cells. SIGNIFICANCE: cIAP2 plays an important role in HCC proliferation and invasion and may exert its effects via the NF-κB signalling pathway.

[Effects of Different Routes in PMSC Transfusion on the Levels of Hematopoietic Regulatory Factors in Aplastic Anemia Rats].

OBJECTIVE: To investigate the effects of different routes in placental mesenchymal stem cells (PMSC) on serum expression levels of IL-4, IL-17, TNF-α and IFN-γ in aplastic anemia (AA) rats. METHODS: The rat model of aplastic anemia (AA rats) was established by 5-fluorouracil combined with busulfan. The rats was divided into four groups: control, experimental, PMSC-injected into the tail vein, and PMSC-injected into the medullary cavity. The general state of rats in each group was observed in detail before and after treatment. The serum levels of interleukin-4 (IL-4) , interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) were measured by enzyme-linked immunosorbent assay (ELISA) at week 1, 3 and 5 after treatment. RESULTS: The serum levels of TNF-α, IFN-γ and IL-17 in the experimental group were significantly higher than those in the control group, while the level of IL-4 was significantly decreased (P＜0.05). The levels of TNF-α, IFN-γ and IL-17 gradually decreased after treatment while the level of IL-4 increased. By the fifth week, the above indexes were closed to the control group (P＞0.05), and the levels of TNF-α, IFN-γ and IL-17 in the group with PMSCs injected via the medullary cavity decrease more significantly than those group with PMSC injected via the tail vein, but level of IL-4 was not significantly different between two groups. CONCLUSION: The level of serum hematopoietic negative regulators increase significantly, and the level of hematopoietic promoting factors decreases significantly in aplastic anemia rats. PMSC can down-regulate the level of hematopoietic negative regulators and up-regulate the level of hematopoietic promoting factors in the rats with aplastic anemia, and the inhibition of hematopoietic negative regulators by intramedullary injection is more significant than that by caudal vein injection.

Inflammation induces stress erythropoiesis through heme-dependent activation of SPI-C.

Inflammation alters bone marrow hematopoiesis to favor the production of innate immune effector cells at the expense of lymphoid cells and erythrocytes. Furthermore, proinflammatory cytokines inhibit steady-state erythropoiesis, which leads to the development of anemia in diseases with chronic inflammation. Acute anemia or hypoxic stress induces stress erythropoiesis, which generates a wave of new erythrocytes to maintain erythroid homeostasis until steady-state erythropoiesis can resume. Although hypoxia-dependent signaling is a key component of stress erythropoiesis, we found that inflammation also induced stress erythropoiesis in the absence of hypoxia. Using a mouse model of sterile inflammation, we demonstrated that signaling through Toll-like receptors (TLRs) paradoxically increased the phagocytosis of erythrocytes (erythrophagocytosis) by macrophages in the spleen, which enabled expression of the heme-responsive gene encoding the transcription factor SPI-C. Increased amounts of SPI-C coupled with TLR signaling promoted the expression of Gdf15 and Bmp4, both of which encode ligands that initiate the expansion of stress erythroid progenitors (SEPs) in the spleen. Furthermore, despite their inhibition of steady-state erythropoiesis in the bone marrow, the proinflammatory cytokines TNF-α and IL-1ß promoted the expansion and differentiation of SEPs in the spleen. These data suggest that inflammatory signals induce stress erythropoiesis to maintain erythroid homeostasis when inflammation inhibits steady-state erythropoiesis.

Monocyte-derived macrophages expand the murine stress erythropoietic niche during the recovery from anemia.

Anemic stress induces a physiological response that includes the rapid production of new erythrocytes. This process is referred to as stress erythropoiesis. It is best understood in the mouse where it is extramedullary and utilizes signals and progenitor cells that are distinct from bone marrow steady-state erythropoiesis. The development of stress erythroid progenitors occurs in close association with the splenic stress erythropoiesis niche. In particular, macrophages in the niche are required for proper stress erythropoiesis. Here we show that the expansion of the niche occurs in concert with the proliferation and differentiation of stress erythroid progenitors. Using lineage tracing analysis in 2 models of anemic stress, we show that the expansion of the splenic niche is due to the recruitment of monocytes into the spleen, which develop into macrophages that form erythroblastic islands. The influx in monocytes into the spleen depends in part on Ccr2-dependent signaling mediated by Ccl2 and other ligands expressed by spleen resident red pulp macrophages. Overall, these data demonstrate the dynamic nature of the spleen niche, which rapidly expands in concert with the stress erythroid progenitors to coordinate the production of new erythrocytes in response to anemic stress.

The intricate role of selenium and selenoproteins in erythropoiesis.

Selenium (Se) is incorporated as the 21st amino acid selenocysteine (Sec) into the growing polypeptide chain of proteins involved in redox gatekeeper functions. Erythropoiesis presents a particular problem to redox regulation as the presence of iron, heme, and unpaired globin chains lead to high levels of free radical-mediated oxidative stress, which are detrimental to erythroid development and can lead to anemia. Under homeostatic conditions, bone marrow erythropoiesis produces sufficient erythrocytes to maintain homeostasis. In contrast, anemic stress induces an alternative pathway, stress erythropoiesis, which rapidly produces new erythrocytes at extramedullary sites, such as spleen, to alleviate anemia. Previous studies suggest that dietary Se protects erythrocytes from such oxidative damage and the absence of selenoproteins causes hemolysis of erythrocytes due to oxidative stress. Furthermore, Se deficiency or lack of selenoproteins severely impairs stress erythropoiesis exacerbating the anemia in rodent models and human patients. Interestingly, erythroid progenitors develop in close proximity with macrophages in structures referred to as erythroblastic islands (EBIs), where macrophage expression of selenoproteins appears to be critical for the expression of heme transporters to facilitate export of heme from macrophage stores to the developing erythroid cells. Here we review the role of Se and selenoproteins in the intrinsic development of erythroid cells in addition to their role in the development of the erythropoietic niche that supports the functional role of EBIs in erythroid expansion and maturation in the spleen during recovery from anemia.

Stress Erythropoiesis Model Systems.

Bone marrow steady-state erythropoiesis maintains erythroid homeostasis throughout life. This process constantly generates new erythrocytes to replace the senescent erythrocytes that are removed by macrophages in the spleen. In contrast, anemic or hypoxic stress induces a physiological response designed to increase oxygen delivery to the tissues. Stress erythropoiesis is a key component of this response. It is best understood in mice where it is extramedullary occurring in the adult spleen and liver and in the fetal liver during development. Stress erythropoiesis utilizes progenitor cells and signals that are distinct from bone marrow steady-state erythropoiesis. Because of that observation many genes may play a role in stress erythropoiesis despite having no effect on steady-state erythropoiesis. In this chapter, we will discuss in vivo and in vitro techniques to study stress erythropoiesis in mice and how the in vitro culture system can be extended to study human stress erythropoiesis.

Effects of heavy metals on health risk and characteristic in surrounding atmosphere of tire manufacturing plant, Taiwan.

The health and environmental effects of metal-containing carbon black (CB) particles emitted from a CB feeding area near a tire manufacturing plant were investigated. The mass ratios of PM1 and PM0.1 (UFPs) relative to TSP were 13.84% ± 4.88% and 50.84% ± 4.29%, respectively. The most abundant elements in all fractions were Fe, Al, and Zn. The mean percentage contributions of Al, Fe, Zn, Cu, and Co to the coarse particles ranged from 49.1% to 69.1%, thus indicating that the Al, Fe, and Zn contents in the CB particles were affected by workplace emissions. The ratios of the total mean deposition fluxes of atmospheric particle-bound heavy metals in the human respiratory tracts of workers/adults, workers/children, and adults/children were approximately 5.5, 11.0, and 2.0, respectively. The integrated risks of five elements via two exposure pathways to adults and children were 1.1 × 10-4 and 1.7 × 10-5, respectively; these numbers reflect the high cumulative carcinogenic risk posed by these toxic metals to local residents (both adults and children; limit, 10-6). These results demonstrate the potential health risk presented by particle-bound heavy metals to humans residing near tire manufacturing plants via inhalation and dermal contact exposure.

Calcium-Sensing Receptor Stimulation in Cultured Glomerular Podocytes Induces TRPC6-Dependent Calcium Entry and RhoA Activation.

BACKGROUND/AIMS: Recent studies provided compelling evidence that stimulation of the calcium sensing receptor (CaSR) exerts direct renoprotective action at the glomerular podocyte level. This protective action may be attributed to the RhoA-dependent stabilization of the actin cytoskeleton. However, the underlying mechanisms remain unclear. METHODS: In the present study, an immortalized human podocyte cell line was used. Fluo-3 fluorescence was utilized to determine intracellular Ca2+ concentration ([Ca2+]i), and western blotting was used to measure canonical transient receptor potential 6 (TRPC6) protein expression and RhoA activity. Stress fibers were detected by FITC-phalloidin. RESULTS: Activating CaSR with a high extracellular Ca2+ concentration ([Ca2+]o) or R-568 (a type II CaSR agonist) induces an increase in the [Ca2+]i in a dose-dependent manner. This increase in [Ca2+]i is phospholipase C (PLC)-dependent and is smaller in the absence of extracellular Ca2+ than in the presence of 0.5 mM [Ca2+]o. The CaSR activation-induced [Ca2+]i increase is attenuated by the pharmacological blockage of TRPC6 channels or siRNA targeting TRPC6. These data suggest that TRPC6 is involved in CaSR activation-induced Ca2+ influx. Consistent with a previous study, CaSR stimulation results in an increase in RhoA activity. However, the knockdown of TRPC6 significantly abolished the RhoA activity increase induced by CaSR stimulation, suggesting that TRPC6-dependent Ca2+ entry is required for RhoA activation. The activated RhoA is involved in the formation of stress fibers and focal adhesions in response to CaSR stimulation because siRNA targeting RhoA attenuated the increase in the stress fiber mediated by CaSR stimulation. Moreover, this effect of CaSR activation on the formation of stress fibers is also abolished by the knockdown of TRPC6. CONCLUSION: TRPC6 is involved in the regulation of stress fiber formation and focal adhesions via the RhoA pathway in response to CaSR activation. This may explain the direct protective action of CaSR agonists.

Dual Alkali Solvent System for CO2 Capture from Flue Gas.

A novel two-aqueous-phase CO2 capture system, namely the dual alkali solvent (DAS) system, has been developed. Unlike traditional solvent-based CO2 capture systems in which the same solvent is used for both CO2 absorption and stripping, the solvent of the DAS system consists of two aqueous phases. The upper phase, which contains an organic alkali 1-(2-hydroxyethyl) piperazine (HEP), is used for CO2 absorption. The lower phase, which consists of a mixture of K2CO3/KHCO3 aqueous solution and KHCO3 precipitate, is used for CO2 stripping. Only a certain kind of amine (such as HEP) is able to ensure the phase separation, satisfactory absorption efficiency, effective CO2 transfer from the upper phase to the lower phase, and regeneration of the upper phase. In the meantime, due to the presence of K2CO3/KHCO3 in the lower phase, HEP in the upper phase is capable of being regenerated from its sulfite/sulfate heat stable salt, which enables the simultaneous absorption of CO2 and SO2/SO3 from the flue gas. Preliminary experiments and simulations indicate that the implementation of the DAS system can lead to 24.0% stripping energy savings compared to the Econamine process, without significantly lowering the CO2 absorption efficiency (∼90%).

Taste disturbance following tongue base resection for OSA.

OBJECTIVES/HYPOTHESIS: To investigate taste disturbance (TD) following endoscopic coblator open tongue base resection (Eco-TBR) for the treatment of obstructive sleep apnea (OSA)-hypopnea syndrome. STUDY DESIGN: A retrospective study in a tertiary academic medical center. METHODS: Eighty patients with OSA who failed continuous positive airway pressure therapy and underwent Eco-TBR for the tongue base obstruction were enrolled in this study. Taste changes and complications were examined before and after surgery. The standard three-drop-method gustatory function test was used to study taste status preoperatively and at 7 days, 1 month, and 3 months postoperatively. RESULTS: Six female and 74 male patients with OSA (mean age, 42.6 years; mean apnea-hypopnea index, 48.9/hour) had a minimum follow-up of 3 months and complete data available for analysis. One patient had postoperative oral bleeding. No long-term obvious dysphagia was encountered. Twelve patients had obvious TD in the four basic tastes (sweet, sour, salty, and bitter). At 3 months postoperative time, eight patients still had changes in taste sensation; however, the TD severity decreased and did not impact the patients' regular social life. The percentage of taste changes by time after Eco-TBR was between 13.8% and 17.5%. CONCLUSION: This study shows Eco-TBR may contribute to postoperative TD. The surgeons should clearly inform the OSA patient about the possibility of TDs after tongue base resection. LEVEL OF EVIDENCE: 4.

The role of TRPC6 in oxidative stress-induced podocyte ischemic injury.

Increasing evidence suggests that ischemia and hypoxia serve important functions in the development of renal diseases. However, the underlying mechanism of ischemic injury has not been fully understood. In this study, we found that renal ischemia-reperfusion injury induced podocyte effacement and the upregulation of TRPC6 mRNA and protein expression. In in vitro experiments, oxygen glucose deprivation (OGD) treatment enhanced the expression of TRPC6 and TRPC6-dependent Ca(2+) influx. TRPC6 knockdown by siRNA interference attenuated the OGD-induced [Ca(2+)]i and actin assembly. OGD treatment also increased ROS production. Furthermore, inhibition of ROS activity by N-acetyl-l-cysteine (NAC) eliminated the OGD-induced increase in TRPC6 expression and Ca(2+) influx. H2O2 treatment, which results in oxidative stress, also increased TRPC6 expression and Ca(2+) influx. We conclude that TRPC6 upregulation is involved in Ca(2+) signaling and actin reorganization in podocytes after OGD. These findings provide new insight into the mechanisms underlying the cellular response of podocytes to ischemic injury.