Analysis of Revision Surgery Following Surgical Reconstruction of the Sigmoid Sinus Wall in Patients with Pulsatile Tinnitus.

BACKGROUND: To explore potential causes leading to the failure of the surgical reconstruction of sigmoid sinus wall in patients with pulsatile tinnitus. METHODS: This study retrospectively analyzed pulsatile tinnitus patients with sigmoid sinus wall dehiscence and/or sigmoid sinus diverticulum, who underwent revision surgeries following the surgical reconstruction of the sigmoid sinus wall. RESULTS: A total of 7 pulsatile tinnitus patients were included. After the first surgery, 5 of 7 patients showed varying degrees of remission in pulsatile tinnitus, but pulsatile tinnitus gradually recurred. The other 2 patients experienced no change in pulsatile tinnitus. Images after the first surgeries revealed that the surgical failure of Patients 1-5 was caused by incompleted elimination of sigmoid sinus wall dehiscence and sigmoid sinus diverticulum. Following revision surgeries, they all acquired great or complete resolution of pulsatile tinnitus. In Patient 6, an abnormal diploic vein entering the sigmoid sinus was overlooked during the first surgery for repairing sigmoid sinus wall dehiscence. As soon as the diploic vein was blocked during the revision surgery, the patient's pulsatile tinnitus was alleviated significantly. Patient 7 had a recurrence of pulsatile tinnitus after transient improvement following the first surgery, and still experienced no change in pulsatile tinnitus after the revision surgery. However, after venous sinus stenting in the stenosis of transverse-sigmoid sinus junction, she got complete resolution of pulsatile tinnitus. It sug- gested that the unresolved stenosis of the venous sinus was the cause of the surgical failure. CONCLUSIONS: Both sigmoid sinus diverticulum and sigmoid sinus wall dehiscence are recommended to be resolved during surgery. Abnormal diploic veins and venous sinus stenosis are potential causes of pulsatile tinnitus.

Clinical Analysis of Ear Congestion after Balloon Eustachian Tuboplasty (BET) with or without Tympanostomy Tube Insertion.

Objective: To explore the clinical analysis of ear congestion after balloon Eustachian tuboplasty (BET) with or without tympanostomy tube insertion. Methods: A total of 35patients (49 affected ears) with ear congestion following BET with or without tympanostomy tube insertion were recruited from the hospitalized patients from January 2015 to December 2017. The score of Eustachian Tube Dysfunction Questionnaire-7 (ETDQ-7) 15, visual analogue scale (VAS), and Valsalva scores were recorded before and after operation, and the influencing factors of prognosis were analyzed. The duration of follow-up was 1-4 years. Results: All patients showed significantly decreased average preoperative ETDQ-7 score, VAS, and Valsalva score after operation (p < 0.05). The significance of the surgery types, course of disease, severity of tympanic membrane retraction, and tympanogram tracings classification as influencing factors of prognosis did not come up to the statistical standard (p > 0.05). Conclusion: The patients showed relatively stable postoperative conditions after 3 years, and there were variations in the range of ETDQ-7 scores at 5 years postoperatively. Patients with levels I and II tympanic membrane retraction showed more favorable surgical effects. Surgical interventions are required for patients diagnosed with obstructive Eustachian tube dysfunction (ETD) after three months of conservative treatment without satisfactory results.

Long noncoding RNA GAS6 antisense RNA1 silencing attenuates the tumorigenesis of acute myeloid leukemia cells through targeting microRNA-370-3p/Tetraspanin3 axis.

PURPOSE: Acute myeloid leukemia (AML) is a type of hematologic malignancy. This study was attempt to explore the effect of long noncoding RNA GAS6 antisense RNA1 (GAS6-AS1) on pediatric AML and the regulation mechanisms. METHODS: GAS6-AS1, microRNA-370-3p (miR-370-3p), and Tetraspanin3 (TSPAN3) expression in bone marrow (BM) tissues and cells was determined by qRT-PCR. The correlation between GAS6-AS1 and clinicopathological features of pediatric patients with AML was assessed. In vitro, viability and migration and invasion of AML cells were evaluated via MTT and transwell assays, respectively. Interactions among GAS6-AS1, miR-370-3p, and TSPAN3 were revealed by dual-luciferase reporter assays. Western blot was applied to confirm the protein expression of TSPAN3. RESULTS: GAS6-AS1 and TSPAN3 expression was elevated in BM tissues of pediatric patients with AML and AML cells, but miR-370-3p expression was reduced. GAS6-AS1 expression was positively related to French-American-British (FAB) classification in pediatric patients with AML. In vitro, GAS6-AS1 deficiency restrained the viability, migration, and invasion of AML cells. Additionally, GAS6-AS1 mediated miR-370-3p expression indeed and TSPAN3 was identified as a target of miR-370-3p. Furthermore, miR-370-3p overexpression repressed the protein expression of TSPAN3. The feedback experiments demonstrated that miR-370-3p inhibition or TSPAN3 overexpression mitigated the suppressive effect of sh-GAS6-AS1 on the tumorigenesis of AML cells. CONCLUSION: GAS6-AS1 silencing restrained AML cell viability, migration, and invasion by targeting miR-370-3p/TSPAN3 axis, affording a novel therapeutic target for pediatric AML.

Recording of electrocochleography from the facial nerve canal in mice.

BACKGROUND: The ever-expanding arsenal of genetically modified mice has created experimental models for studying various mechanisms of deafness. Electrocochleography (ECochG) is a recording technique of cochlear potentials evoked by sound stimulation, which was widely used to evaluate the cochlear hearing function. However, there is currently a lack of information on long-term recording technology of ECochG in mice. NEW METHOD: We describe in detail the surgical procedure of implanting electrode into the facial nerve canal in C57BL/6J mice for ECochG recording. The results of ECochG recorded by electrode in the facial nerve canal were compared with ECochG guided by electrode on the round window niche. RESULTS: The surgical method of inserting the electrode into the facial nerve canal is relatively simple and can be completed within 15 min. The electrode inserted into the elongated facial nerve canal is stable and close to the auditory nerve trunk, so it is conducive to long-term auditory function monitoring. Hence, the ECochG guided by the electrode from the facial nerve canal can maintain a stable response for more than two weeks. In contrast, the ECochG guided by the electrode in the round window niche can only be maintained for a maximum of 20 min. COMPARISON WITH EXISTING METHODS: In mice, existing recording techniques of ECochG from round window niche is limited by conductive hearing loss due to middle ear effusion or surgical damage. CONCLUSIONS: ECochG recording from the facial nerve canal is suitable for long-term recording in mice. This electrode approach provides a repeatable and reliable measurement of ECochG.

Long-Term Effects of Zinc Deficiency and Zinc Supplementation on Developmental Seizure-Induced Brain Damage and the Underlying GPR39/ZnT-3 and MBP Expression in the Hippocampus.

We previously illustrated that long-term upregulated expression of ZnT-3 in the hippocampus of rats that underwent neonatal seizures was restored by pretreatment with a ketogenic diet. It was recently demonstrated that upregulated expression of ZnT-3 was associated with increased concentrations of intracellular free zinc ions in an in vitro model of glutamate-induced hippocampal neuronal excitotoxic damage. However, there is still a lack of research on the effects of different concentrations of zinc in the diet on developmental convulsive brain injury. The aim of this study was to investigate the effects of different zinc concentrations in the diet on long-term neurobehavioral and seizure thresholds following lithium chloride-pilocarpine-induced developmental seizures. Sprague-Dawley rats (postnatal day 27, P27) were randomly assigned to one of six dietary groups for 4 weeks: normal zinc control group (Control group, 44 mg/kg Zn), Zn-deficient control group (ZD group, 2.7 mg/kg Zn), Zn supplemented control group (ZS group, 246 mg/kg Zn), pilocarpine-induced seizure plus regular zinc diet group (SE group, 44 mg/kg Zn), seizure plus low-zinc diet group (SE + ZD group, 2.7 mg/kg Zn), and seizure plus high-zinc diet group (SE + ZS group, 246 mg/kg Zn). Novel object recognition and passive avoidance tests were performed on rats at P42 and P56. After routine seizure threshold detection and Timm staining procedures at P57, expression of GPR39, ZnT-3, and MBP were detected in the hippocampus by Western blot analysis. The results revealed that the Zinc-deficient diet for 4 weeks aggravated the long-term adverse effects of developmental seizures, evidenced by weight, cognition, seizure threshold and serum zinc concentrations, which were paralleled by expression changes in hippocampal GPR39 and ZnT-3. In contrast, zinc supplementation for 4 weeks significantly improved damage-related changes described above and rescued the abnormal expression of GPR39, ZnT-3, and MBP in the hippocampus. Similar alterations between the expression pattern of MBP and aberrant sprouting of mossy fibers in the hippocampus may indicate that sprouting is a secondary pathological change caused by developmental brain damage rather than the cause of epileptogenesis. Up-regulation of MBP protein levels in the high zinc diet-treated seizure group as well as the corresponding improvement of cognitive impairment and reduced hippocampal mossy fiber regenerative sprouting, may represent a compensatory mechanism for neuronal membrane damage and repair.

Quantum Dot Cellular Uptake and Toxicity in the Developing Brain: Implications for Use as Imaging Probes.

Nanometer-sized luminescent semiconductor quantum dots (QDs) have been utilized as imaging and therapeutic agents in a variety of disease settings, including diseases of the central nervous system. QDs have several advantages over traditional fluorescent probes including their small size (5-10 nm), tunable excitation and emission spectra, tailorable surface functionality, efficient photoluminescence, and robust photostability, which are ideal characteristics for in vivo imaging. Although QDs are promising imaging agents in brain-related applications, no systematic evaluation of QD behavior in brain-relevant conditions has yet been done. Therefore, we sought to investigate QD colloidal stability, cellular uptake, and toxicity in vitro, ex vivo, and in vivo in the brain environment. We found that QD behavior is highly dependent on surface functionality and that treatment of cultured organotypic whole hemisphere (OWH) slices with QDs results in dose-dependent toxicity and metallothionein increase, but no subsequent mRNA expression level changes in inflammatory cytokines or other oxidative stress. QDs coated with poly(ethylene glycol) (PEG) were protected from aggregation in neurophysiologically relevant fluids and in tissue, allowing for greater penetration. Importantly, QD behavior differed in cultured slices as compared to monolayer cell cultures, and behavior in cultured slices aligned more closely with that seen in vivo. Irrespective of surface chemistry and brain-relevant platform, non-aggregated QDs were primarily internalized by microglia in a region-dependent manner both in slices and in vivo upon systemic administration. This knowledge will help guide further engineering of candidate QD-based imaging probes for neurological application.

Qualitative assessment of extractables from single-use components and the impact of reference standard selection.

The advent of single-use bioprocess systems used for the delivery, storage or manufacture of biopharmaceuticals has introduced a new potential source for extractables and leachables (E&L) as these systems are comprised of polymeric materials. Several industry working groups, the FDA and USP have issued guidance and draft guidance on E&L analyses for a variety of applications. These documents typically indicate that mass spectrometry should be applied for discovery of E&L's but provide little guidance as to the exact analytical methodology which should be used. We investigated the extractable profiles of a model single-use bioprocessing system consisting of a single-use bioprocess bag, connector tubing, and a hydrophilic disk filter including filter housing. Extractions were performed in water, ethanol, ethanol/water (50:50) and saline solutions. Extracts were analyzed using a stepwise analytical methodology including a variety of screening and mass spectrometry methods We then used this model system to demonstrate the use of recursive feature finding to automatically detect unique extractables followed by statistical filtering to focus on differentially present extractables which were above the analytical evaluation threshold (AET). We further show the significant affects of standard selection on the number of compounds determined to be above AET when reducing liquid chromatography-mass spectrometry (LC/MS) data. A relative response factor database consisting of 14 structurally diverse commercially available polymer additives was used to arrive at an LC/MS identification threshold. The results of this study demonstrate that significant care should be taken when selecting standards for LC/MS analysis to avoid under reporting of extractables and leachables.

Effect of otitis media with effusion and its clinical intervention on the development of mastoid in children.

CONCLUSION: Otitis media with effusion (OME) can affect the development of mastoid in children. For younger children (<12 years old), surgical intervention may promote the development of mastoid. It is highly recommended that patients with severe tympanic membrane retraction have tympanostomy tubes to improve the circulation in the middle ear as early as possible. OBJECTIVE: To investigate the effect of OME and its clinical intervention on the development of mastoid in children. METHODS: A total of 46 children with OME were divided into 2 groups according to their ages. In group 1, 26 cases (0-6 years old) were treated for approximately 2 months, while in group 2, 20 cases (7-15 years old) were treated for 10 months. The treatments included tympanic effusion incision or catheterization, and adenoidectomy and/or bilateral tonsillectomy. Before and 6 months after treatments, patients were examined by bilateral temporal bone CT scanning, pure-tone audiometry, and tympanometry. 3-D volumetric reconstruction was then performed to determine the morphological properties of each patient's mastoid. RESULTS: After a 2-month comprehensive treatment, the volume of mastoid was close to that in normal children, indicating that it could return to normal level if the treatment was completed within 2 months. In group 2, the results suggested that if the treatment lasted more than 6 months, the development of mastoid would be stalled.

[Simulation of the effects of climate change on canopy transpiration over a broad-leaved Korean pine forest in Changbai Mountains].

To investigate the effects of climate change on canopy transpiration, a process-based carbon and water coupling multi-layer model was verified, and used to simulate the canopy transpiration over a broad-leaved Korean pine forest in Changbai Mountains. This multi-layer model could well estimate canopy transpiration. The simulated values fitted well with the measured data based on eddy covariance method. The simulation of the responses of canopy transpiration to climate change indicated that the latent heat flux (LE) increased with increasing air temperature, and decreased with the decline of soil water content or the increase of air CO2 concentration. Under the climate scenarios in this study, the LE was most sensitive to the associated variation of 10% reduction of soil water content in 0-20 cm layer and 190 micromol x mol(-1) increase of CO2 concentration, but not sensitive to the synchronous variation of 10% reduce of soil water content and 3.6 degrees C increase of air temperature.

[Energy balance and evapotranspiration in broad-leaved Korean pine forest in Changbai Mountains].

Based on the continuous measurements of an open-path eddy covariance system, this paper analyzed the characteristics of energy balance components and evapotranspiration in a broad-leaved Korean pine forest in Changbai Mountains in 2008, as well as the differences of energy balance components and evapotranspiration between growth season and dormant season. For the test forest, the year-round energy balance closure was 72%, being at a medium level, compared to the other studies in the Fluxnet community. The energy balance components had significant differences in their diurnal and seasonal variations. In growth season, turbulent energy exchange was dominated by upward latent heat flux, accounting for 66% of available energy; while in dormant season, the turbulent energy exchange was dominated by upward sensible heat flux, accounting for 63% of available energy. The accumulated annual evapotranspiration in the study site in 2008 was 484.7 mm, occupying 87% of the precipitation at the same time period (558.9 mm), which demonstrated that evapotranspiration was the main water loss item in temperate forests of northern China.