Factors Influencing the Fasting Time in Adult Patients After the Endoscopic Management of Sharp Esophageal Foreign Bodies.

Background: Sharp esophageal foreign body (SEFB) impaction can cause varying degrees of damage to the esophagus. There are few studies analyzing the postoperative fasting time in SEFB patients. Methods: We retrospectively collected 835 SEFB patients. According to the fasting time after the endoscopic removal (ER) of SEFBs, the patients were divided into two groups: short fasting time (SFT, fasted ≤24 h) and long fasting time (LFT, fasted >24 h). Results: There were 216 and 619 patients in the SFT and LFT group, respectively. The average age of the SFT group (52.97 years) was younger than that of the LFT group (55.96 years) (p = 0.025). The LFT group had lower proportion of duration of impaction (DOI) within 12 hours (14.2% vs 22.2%, p = 0.006) and erosion rates (89.0% vs 94.0%, p = 0.034) as well as higher proportion of esophageal perforation (19.5 vs 6.5%, p = 0.010) and patients who got intravenous anesthesia (63.78% vs 31.9%, p = 0.000) than the SFT group. The longest diameter of the foreign body (Lmax) in the LFT group (2.60 ± 1.01 cm) was greater than that in the SFT group (2.41 ± 0.83 cm; p = 0.01). Multivariate regression analysis found that age (OR = 1.726[1.208-2.465], p = 0.003), DOI (OR = 1.793[1.175-2.737], p = 0.007), Lmax (OR = 1.477[1.033-2.111], p = 0.032), perforation (OR = 3.698[2.038-6.710]; p < 0.01) and intravenous anesthesia (OR = 3.734[2.642-5.278]; p < 0.01) were the independent factors that prolonged fasting time in patients with SEFBs, while esophageal mucosal erosion (OR = 0.433[0.229-0.820]; p = 0.01) was the influencing factor leading to shortened fasting time. Conclusion: For the first time, we analyzed factors influencing the fasting time after ER in SEFB patients. Age, DOI, Lmax, perforation and intravenous anesthesia were risk factors for a prolonged postoperative fasting time.

A first-in-human phase 1 study of simnotrelvir, a 3CL-like protease inhibitor for treatment of COVID-19, in healthy adult subjects.

Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence of adverse events (AEs) was 22.2% (17/72) and 6.3% (1/16) in intervention and placebo groups, respectively. The simnotrelvir apparent clearance was 135-369 L/h with simnotrelvir alone, and decreased significantly to 19.5-29.8 L/h with simnotrelvir/ritonavir. The simnotrelvir exposure increased in an approximately dose-proportional manner between 250 and 750 mg when co-administered with ritonavir. After consecutive twice daily dosing of simnotrelvir/ritonavir, simnotrelvir had a low accumulation index ranging from 1.39 to 1.51. The area under the curve of simnotrelvir increased 44.0 % and 47.3 % respectively, after high fat and normal diet compared with fasted status. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90 % inhibition of SARS-CoV-2 in vitro at 750 mg/100 mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen.

A first-in-human phase I study of SHR-1906, a humanized monoclonal antibody against connective tissue growth factor, in healthy participants.

New therapeutic targets and drugs are urgently needed to halt the fibrosing process in idiopathic pulmonary fibrosis (IPF). SHR-1906 is a novel fully humanized monoclonal antibody against the connective tissue growth factor, which plays an essential role in the genesis of IPF. We assessed the safety, tolerability, pharmacokinetics (PKs), and immunogenicity of single dose SHR-1906 in healthy participants. This was a randomized, double-blind, placebo-controlled, dose-escalation, phase I study. Twelve healthy participants for each dose level were enrolled to receive single ascending doses of SHR-1906 intravenously (1.5, 6, 12, 20, 30, and 45 mg/kg) or placebo and followed for 71 days. The primary end points were safety and tolerability. Treatment-related treatment-emergent adverse events occurred in 25 participants (46.3%) in the SHR-1906 group and 11 (61.1%) in the placebo group. No serious adverse events occurred. Over the dose range investigated, the geometric mean clearance was 0.14-0.63 mL/h/kg, the geometric mean volume of distribution at steady-state was 47.4-75.5 mL/kg, and the terminal elimination half-life was 51.9-349 h. SHR-1906 showed nonlinear PKs. The peak concentration increased in a dose-proportional manner, whereas the area under the concentration-time curve showed a greater than dose-proportional increase. Anti-drug antibodies of SHR-1906 were detected in nine of 54 participants (16.7%). A single dose of SHR-1906 up to 45 mg/kg demonstrated a favorable tolerability profile in healthy participants. The PKs and immunogenicity of SHR-1906 were evaluated, supporting further clinical development.

Changes in brain gray matter volume in nasopharyngeal carcinoma patients after radiotherapy in long-term follow-up

Abstract Objectives The aim of this study was to examine the changes in gray matter in nasopharyngeal carcinoma patients with normal hearing (Group 1) and nasopharyngeal carcinoma patients with hearing loss (Group 2) after radiotherapy using voxel-based morphological analysis and to analyze the relationship with the radiation doses of the temporal lobe. Methods 21 patients in Group 1, 14 patients in Group 2, and 21 healthy volunteers were selected. All participants underwent an otologic examination and three-dimensional magnetization preparatory rapid acquisition gradient echo sequence scan. The correlation between the variation of whole brain gray matter volume and the doses of the temporal lobe was analyzed by Data Processing & Analysis for Brain Imaging software. Results Compared with the normal control group, the brain areas with reduced gray matter volume in nasopharyngeal carcinoma patients after radiotherapy were mainly in the left posterior cerebellar lobe (T = −8.797), left insular lobe (T = −7.96), and the right insular lobe (T = −6.632). Compared to Group 1, the brain areas of Group 2 patients with reduced gray matter volume were mainly in the left superior temporal gyrus (T = −2.366), left olfactory bulb (T = −2.52), left Rolandic operculum (T = −2.431), and right olfactory bulb (T = −3.100). Compared with Group 1, the brain areas of Group 2 patients with increased gray matter volume were mainly in the left calcarine sulcus (T = 3.425) and right calcarine sulcus (T = 3.169). There were no correlations between the changes of brain gray matter volume and the radiation doses of the temporal lobe in both Group 1 and Group 2. Conclusions The radiotherapy may cause the changes of brain areas associated with cognitive function in nasopharyngeal carcinoma in a long-term follow-up. At the same time, nasopharyngeal carcinoma patients with the radiation-induced hearing loss had abnormal gray matter volumes in the auditory center and other sensory centers. Our findings might provide new understanding into the pathogenesis of radiation-induced brain damage in normal-appearing brain tissue. Yet this exploratory study should be taken with caution.

Changes in brain gray matter volume in nasopharyngeal carcinoma patients after radiotherapy in long-term follow-up.

OBJECTIVES: The aim of this study was to examine the changes in gray matter in nasopharyngeal carcinoma patients with normal hearing (Group 1) and nasopharyngeal carcinoma patients with hearing loss (Group 2) after radiotherapy using voxel-based morphological analysis and to analyze the relationship with the radiation doses of the temporal lobe. METHODS: 21 patients in Group 1, 14 patients in Group 2, and 21 healthy volunteers were selected. All participants underwent an otologic examination and three-dimensional magnetization preparatory rapid acquisition gradient echo sequence scan. The correlation between the variation of whole brain gray matter volume and the doses of the temporal lobe was analyzed by Data Processing & Analysis for Brain Imaging software. RESULTS: Compared with the normal control group, the brain areas with reduced gray matter volume in nasopharyngeal carcinoma patients after radiotherapy were mainly in the left posterior cerebellar lobe (T = -8.797), left insular lobe (T = -7.96), and the right insular lobe (T = -6.632). Compared to Group 1, the brain areas of Group 2 patients with reduced gray matter volume were mainly in the left superior temporal gyrus (T = -2.366), left olfactory bulb (T = -2.52), left Rolandic operculum (T = -2.431), and right olfactory bulb (T = -3.100). Compared with Group 1, the brain areas of Group 2 patients with increased gray matter volume were mainly in the left calcarine sulcus (T=3.425) and right calcarine sulcus (T=3.169). There were no correlations between the changes of brain gray matter volume and the radiation doses of the temporal lobe in both Group 1 and Group 2. CONCLUSIONS: The radiotherapy may cause the changes of brain areas associated with cognitive function in nasopharyngeal carcinoma in a long-term follow-up. At the same time, nasopharyngeal carcinoma patients with the radiation-induced hearing loss had abnormal gray matter volumes in the auditory center and other sensory centers. Our findings might provide new understanding into the pathogenesis of radiation-induced brain damage in normal-appearing brain tissue. Yet this exploratory study should be taken with caution.

Population pharmacokinetics and pharmacogenetics of apatinib in adult cancer patients.

AIMS: Apatinib is widely used in Chinese cancer patients. As the in vivo drug disposition of apatinib has large individual differences, adverse events are prone to occur. Cytochrome P450 (CYP)3A5 and cancer types maybe the main factors affecting this individual differences. The objective of our study was to establish a population pharmacokinetics (PK) model of apatinib in adult cancer patients, and to explore optimal dosage regimens for individualized treatment. METHODS: Adult patients with various types of cancer treated with apatinib were enrolled. The concentration of apatinib in plasma was determined by high-performance liquid chromatography-tandem mass spectrometry. CYP3A5 genotype was determined using TaqMan allelic discrimination technique. The population PK model was developed by NONMEM V7.4. The dosing regimen was optimized based on Monte Carlo simulations. RESULTS: A population PK model of apatinib in adult cancer patient was established. CYP3A5 genotype and systemic cancer type (digestive system cancers, nondigestive system cancers) were the most significant covariates for PK parameters. Patients with CYP3A5*1 expressers (CYP3A5*1/*1 and CYP3A5*1/*3) had lower apparent clearance and apparent volume of distribution than patients who do not express CYP3A5*1 (CYP3A5*3/*3). Patients with nondigestive system cancer had higher apparent volume of distribution and absorption rate constant than digestive system cancer. The results of dose simulation suggest that the apatinib dose in patients who do not express CYP3A5*1 should be 33.33-50.00% higher than that in CYP3A5*1 expressers. CONCLUSIONS: A population PK model of apatinib in adult cancer patients was established. CYP3A5 genotype and systemic cancer type had concurrent effects on PK parameters. CYP3A5 patients who do not express CYP3A5*1 required higher doses.

Pharmacokinetics and bioavailability of a new long-acting insulin analog in healthy Chinese volunteers: an open, randomized, single-dose, two-period and two-sequence cross-over study.

Objectives: INS068 is a novel, soluble, and long-acting insulin analog. In this study, we evaluated the pharmacokinetics and relative bioavailability of two formulations of INS068 in healthy Chinese subjects: a reference formulation packaged in vials and administered via syringe (R), and a test formulation packaged and administered via pen injector (T). Methods: A randomized, open-label, two-period, two-sequence crossover study was conducted with 24 healthy Chinese subjects. Subjects were randomized and administered subcutaneously in the abdomen at 0.4 U/kg of test or reference INS068 injection according to an open crossover design. INS068 concentrations in the serum were measured using LC-MS/MS, and the pharmacokinetic parameters of maximum concentration (Cmax) and area under the concentration-time curve (AUC0-t and AUC0-∞) were used to evaluate relative bioavailability. Results: After a single dose at 0.4 U/kg, the median Tmax of INS068 was 12 h for both formulations, and the mean t1/2 for T and R was 13.0 h and 12.6 h, respectively. The geometric means of Cmax and AUC0-∞ were 3.99 nmol/L and 120 h·nmol/L for the T, and 4.05 nmol/L and 117 h·nmol/L for the R, respectively. The geometric mean ratios of Cmax, AUC0-t and AUC0-∞ of T over R were 98.7% (90% CI: 92.7%-105.2%), 102.6% (90% CI: 100.0%-105.3%) and 102.8% (90% CI: 100.1%-105.5%). Conclusion: The overall PK profile of the two formulations of INS068 injection was comparable in healthy subjects, and the pen injector of INS068 had adequate safety and tolerability, supporting it as a new formulation in a phase III study and bridging PK data from early phase clinical trials. Clinical Trial Registration: clinicaltrials.gov, identifier: NCT05336071.

Prognostic Profiling of the EMT-Associated and Immunity-Related LncRNAs in Lung Squamous Cell Carcinomas.

Lung squamous cell carcinoma (Lung SCC) is associated with metastatic disease, resulting in poor clinical prognosis and a low survival rate. The aberrant epithelial-mesenchymal transition (EMT) and long non-coding RNA (LncRNA) are critical attributors to tumor metastasis and invasiveness in Lung SCC. The present study divided lncRNAs into two subtypes, C1 and C2 (Cluster 1 and Cluster 2), according to the correlation of EMT activity within the public TCGA and GEO databases. Subsequently, the differential clinical characteristics, mutations, molecular pathways and immune cell deconvolution between C1 and C2 were evaluated. Lastly, we further identified three key lncRNAs (DNM3OS, MAGI2-AS3 and LINC01094) that were associated with EMT and, at the same time, prognostic for the clinical outcomes of Lung SCC patients. Our study may provide a new paradigm of metastasis-associated biomarkers for predicting the prognosis of Lung SCC.

Manganese and dysprosium codoped carbon quantum dots as a potential fluorescent/T1/T2/CT quadri-modal imaging nanoprobe.

It has been challenging to integrate various medical imaging modalities into an ultra-small nanoparticle with good biocompatibility to build highly efficient multimodal imaging nanoprobes. A new manganese and dysprosium codoped carbon quantum dots (Mn,Dy-CQDs) with a mean diameter of 1.77 nm was synthesized for fluorescence imaging,T1/T2-weighted magnetic resonance imaging (T1/T2-weighted MRI), and x-ray computed tomography (CT) imaging using a simple one-step hydrothermal approach. The obtained Mn,Dy-CQDs showed good water solubility, long-term stability, strong stable fluorescence property (fluorescence quantum yield of 31.62%), and excellent biocompatibility. The cell imaging verified that the Mn,Dy-CQDs have high efficiency of fluorescence imaging. The Mn,Dy-CQDs, on the other hand, had a superior x-ray absorption performance (47.344 HU l g-1), a higher longitudinal relaxivity (r1 = 7.47 mM-1s-1), a higher transverse relaxivity (r2 = 42.686 mM-1s-1).In vitroT1/T2-weighted MRI and CT imaging showed that Mn,Dy-CQDs can produce a strong contrast enhancement impact. To summarise, the Mn,Dy-CQDs may be used as aT1/T2-weighted MRI/CT/fluorescent quadri-modal imaging nanoprobe, indicating that they have a lot of uses in biomedical multimode imaging and clinics.

Anatomic Measurements of Distances from Lateral Surface of Cranium to Cochlea in Congenital Aural Atresia and Stenosis Patients.

INTRODUCTION: Studies have shown that higher response levels can be obtained when the bone conduction stimulation position is closer to the cochlea. However, the morphological characteristics of round window niche and posterior tympanum in congenital aural atresia (CAA) and stenosis (CAS) patients were different from the normal. These affected the position of the cochlea at the cranial base. It was still unknown whether the distances from the cranium of CAA and CAS patients to the cochlea were the same as those of normal patients or not. OBJECTIVE: To measure distances from various points on the lateral surface of the cranium to the cochlea and the cranium thickness on these points among a CAA group, CAS group and normal control group, which may provide valuable information for the better position of bone conduction stimulation. METHODS: CT images of CAA, CAS patients and these patients' healthy sides were analyzed. Firstly, the Frankfurt horizontal plane (Pfrkt) was established. Secondly, a model of part of the cranium was three-dimensionally reconstructed. Then, the Pfrkt plane was rotated down 20, 30 and 40° according to the superior margin of the external auditory canal. At every angle, points 25, 30, 35 and 40 mm away from the superior margin of the external auditory canal were marked out on the surface of the model and recorded as P20A, P30A, P40A, P20B, etc. The spatial distances between the cranium and ipsilateral cochlea were defined as lengths of points on the surface of the model to the cochlea apex (CA), cochlear base (CB) and modiolus midpoint (MM), respectively, recorded as P20A/CA, P20A/CB, P20A/MM, P30A/CA, etc. Results and Conclusions: In all groups, the length of P20D/CA was the shortest compared to P30D/CA and P40D/CA (p < 0.05). The P20A/CB and P20A/MM were also the shortest (p < 0.05). When the Pfrkt plane was rotated down 30 and 40°, the results were the same as at 20° (p < 0.05). However, P20D, P30D and P40D were almost on the mastoid air cells. We suggest that the bone conduction stimulation position is placed closer to the ear, while avoiding the mastoid air cells in the CAA and CAS patients.

Relationship between short-term and mid-term hearing outcomes after stapedotomy in patients with otosclerosis: an investigation.

BACKGROUND: Although stapedotomy is effective for patients with clinical otosclerosis, the time of hearing stabilization has not yet been consistent. OBJECTIVE: To investigate the relationships between post-operative follow-up times, hearing outcomes, and threshold shift after stapedotomy. MATERIALS AND METHODS: Fifty-five patients with clinical otosclerosis that underwent stapedotomy were retrospectively studied. Pure tone audiometry tests were conducted within the first month (short-term) and within 1 year (mid-term) postoperatively. Data were analyzed for two rounds of audiometry tests at different postoperative follow-up times. RESULTS: Air conduction (AC) and bone conduction (BC) were significantly correlated with preoperative hearing levels (p<.01). AC, BC, and air bone gap (ABG) significantly improved at the short-term (p<.001) and continued to improve at the mid-term (p<.01). The success rate of surgery increased from 87% at short-term to 98% at mid-term. Less than 1/3 of cases encountered BC deterioration at short-term, whereas most improved at mid-term. CONCLUSIONS: Hearing results showed a trend of improvement between short-term and mid-term follow-ups after stapedotomy. AC, ABG, and success rate displayed significant improvement several months postoperatively. BC deterioration occurred in less than 30% of patients at short-term. The recovery of BC at 4 kHz was later than that of low frequencies.

Synonymous mutation rs2515641 affects CYP2E1 mRNA and protein expression and susceptibility to drug-induced liver injury.

Aim: To evaluate whether the synonymous mutant rs2515641 could affect cytochrome P450 2E1 (CYP2E1) expression and the response to acetaminophen (APAP) or triptolide (TP) treatment. Materials & methods: HepG2 cells were transfected with lentiviral vector containing either CYP2E1-1263C or CYP2E1-1263T. Some of these recombinant cells were then treated with APAP or TP. CYP2E1 gene expression was detected by PCR and western blot. Results:CYP2E1 gene expression decreased significantly both in mRNA and protein level after rs2515641 mutation, indicating that this polymorphism can affect both transcription and translation. Furthermore, rs2515641 mutation dramatically changes the response of CYP2E1 expression to APAP or TP treatment. Conclusion: Rs2515641 significantly changes CYP2E1 expression and function, which would be expected to affect drug disposition and response.

Pharmacokinetics and vasodilating effect study of beraprost sodium in healthy volunteers.

Currently beraprost sodium (BPS) is widely proposed to ameliorate the symptoms caused by chronic arterial occlusive disease. The objective of this study is to investigate the BPS pharmacokinetic characteristics, its vasodilating effect and the relationship between plasma concentration vs response effect. 12 healthy Chinese volunteers (6 male, 6 female) were chosen to participate in a single center, random, and open design study. After overnight fasting, BPS (dose = 40µg) was administrated orally to each volunteer. The blood samples were collected at different time points (from 0 to 5 h after administration) and BPS concentration was analyzed by LC-MS/MS method. The vasodilating effect was evaluated by detecting the skin microcirculation blood flow of volunteers' fingers with laser Doppler fluxmetry. The Cmax of BPS was (601.14 ± 214.81) pg/mL, the Tmax was (0.58 ± 0.48) h, and AUC0-t was (1020.41±214.63) pg/mL•h. BPS exhibited significant vasodilating effect since the skin microcirculation blood flow increased definitely at 0.25, 0.5, and 0.75 h (all p<0.05) after drug administration, and a positive correlation was presented between the pharmacokinetics and the vasodilating effect, which would be beneficial for guiding BPS dosage in clinical.

CYP2E1 and miRNA-378a-3p contribute to acetaminophen- or tripterygium glycosides-induced hepatotoxicity.

Increased expression of CYP2E1 may represent the main factor contributing to oxidative stress-mediated liver damage in drug-induced liver injury (DILI). However, the regulation mechanism of CYP2E1 expression is poorly described. The present study was aimed to investigate the role of CYP2E1 in acetaminophen (APAP)- or tripterygium glycosides (TG)-induced hepatotoxicity as well as the regulation of CYP2E1 and miR-378a-3p expression by APAP or TG. Rats were randomly divided and treated with APAP, TG, chlormethiazole (CMZ), APAP + CMZ and TG + CMZ, respectively, for 4 weeks. Then, blood and liver samples were collected. Serum and hepatic biochemical parameters were measured using commercial kits. Liver histopathology was tested by H&E staining. Expression levels of CYP2E1 mRNA and miR-378a-3p were detected by qRT-PCR. CYP2E1 protein expression was determined by Western blot. Our results showed that CMZ effectively restored the hepatic histopathological changes, oxidative stress biomarkers and TNF-α levels induced by APAP or TG. CYP2E1 mRNA and/or protein expression levels were dramatically increased after chronic APAP or TG treatment, while this induction was significantly reversed by CMZ co-treatment. Of note, miR-378a-3p expression levels were significantly suppressed after APAP, TG and/or CMZ treatment. These results suggested that CYP2E1 were highly induced after chronic APAP or TG treatment, which in turn play an important role in APAP- or TG-induced hepatotoxicity. These inductions of CYP2E1 expression were probably carried out by inhibition of miR-378a-3p. Our findings might provide a new molecular basis for DILI.

Effect of Oval Window Blockage on Bone Conduction in Cadaver Heads.

OBJECTIVE: This study aimed to explore the feasibility of medical adhesive in the molding of oval window (OW) blockage in cadaver heads and to study the effect on bone conduction (BC). METHODS: Four cadaver heads were selected to establish OW blockage model. The daub type of medical adhesive was used to immobilize OW. The vibration properties of the round window membrane (VRWM) in response to the acoustic stimulation, and the vibration properties of the round window membrane and cochlear promontory (VCP) in response to the BC transducer B-71 stimulation were assessed by laser Doppler vibrometer in both pre-OW blockage and post-OW blockage. RESULTS: After blocking the oval window, the mean values of the sound-induced velocities amplitude responses of the round window membrane by air conduction were decreased significantly beyond 30 dB in all measured frequencies (p < 0.05). The round window membrane relative velocity (VRWM/VCP) shows a decrease of about 1 dB at 1 and 3 kHz frequencies and a slight increase of around 0.5 dB from 4 to 8 kHz frequencies in post-OW blockage. However, it should also be noted that the VRWM/VCP is a significant decrease of 1.2 dB at 3 kHz in post-OW blockage compared with pre-OW blockage (p < 0.05). CONCLUSION: Medical adhesive was available for the immobilization of oval window. In cadaver heads, the effect of OW blockage on the BC was the notching at 3 kHz.

Bone conduction hearing in the blockage of oval and/or round windows in cats.

BACKGROUND: Simple or non-syndromic types of oval window (OW) or round window (RW) atresia are relatively rare in clinical. Few studies have assessed bone conduction (BC) hearing in OW or RW atresia patients, with some reporting that BC hearing lies within the normal range, whereas others observing impaired BC hearing. AIMS/OBJECTIVES: This study explored the effect of blocking the OW and RW during BC in cat models. MATERIAL AND METHODS: Twenty-four cats were randomly divided into three immobilization groups (OW blockage, RW blockage, and OW + RW blockage) and control group. Each immobilization group also had the initial control state before blockage. Medical adhesive and ear mould glue were used to immobilise the stapes footplate and RW, respectively. Comparisons were made of the auditory brainstem response (ABR) thresholds before and after immobilization for the three immobilization groups during three different stimuli [air conduction (AC) click, BC click, and BC pure tones]. RESULTS: The AC click thresholds increased after immobilisation in three experimental groups compared to the control group (p < .05). The AC click thresholds increased compared to their initial control state after all three immobilization groups (p < .05). With an increase in frequency from 2 to 8 kHz, there was a general decrease in the difference between pre- and post-immobilization BC hearing thresholds in all three immobilization groups. The BC click threshold and BC tone thresholds at 2-4 kHz in both OW blockage and OW + RW blockage groups exceeded those in RW blockage group (p < .05). CONCLUSIONS AND SIGNIFICANCE: The use of medical adhesive and ear mould glue for the blockages of OW and RW, respectively in cats was feasible. The effect of blocking the OW and RW in BC hearing was larger at low frequencies than high frequencies between 2 and 8 kHz. OW blockage had a greater effect than RW blockage on BC hearing at 2-4 kHz range.

Round Window Occlusion Affects Bone Conduction in Cadaver Heads.

OBJECTIVE: To explore the feasibility of ear mold glue in the molding of round window occlusion (RWO) in cadaver heads and to study the effect on bone conduction (BC). METHODS: Ten cadaver heads were selected to establish RWO model. Ear mold glue was used to immobilize round window niche. The vibration properties of the stapes footplate (VST) in response to the acoustic stimulation, and the vibration properties of the stapes footplate and cochlear promontory (VCP) in response to the B-71 stimulation were assessed by laser Doppler vibrometer in both pre-RWO and post-RWO. RESULTS: The mean velocities of the stapes footplate in response to the acoustic stimulation in post-RWO were decreased significantly beyond 14 dB for frequency from 0.5k to 3k Hz and decreased beyond 11 dB for frequency above 4 kHz compared with pre-RWO (p<0.05). The stapes footplate relative velocity (VST/VCP) for pre-RWO and post-RWO conditions showed almost no difference (the difference was around 0.5 dB for 0.5k, 1k, 2k, 5k, 6k, and 7k Hz frequencies), except a slight decrease of around 1.5 dB at 3k and 8k Hz frequencies in post-RWO. However, the VST/VCP was a significant decrease of 1.7 dB at 4k Hz in post-RWO compared with Pre-RWO (p<0.05). CONCLUSION: Ear mold glue was available for the immobilization of round window niche in cadaver heads. The RWO have an impact on the BC hearing threshold. The effect of RWO on the BC was similar to that of otosclerosis, but the feature frequency for the depressed BC threshold at 4k Hz.

Age-related changes in the morphological relationship between the supratubal recess and the Eustachian tube.

OBJECTIVE: To study age-related changes in the morphology of the supratubal recess (STR) and its relationship with the Eustachian tube (ET). METHODS: Seventy randomly selected computed tomography (CT) images of non-pathological temporal bones of 49 patients were reviewed retrospectively. The patients were grouped according to age into 4 age groups: group A (0-3 years), group B (4-8 years), group C (9-18 years) and group D (19-50 years). Space analytic geometry was assessed to directly calculate the morphology of the STR and the ET. RESULTS: In normal temporal bones, the STR was mostly presented with a solitary cell in life. The length of the STR was significantly longer in group C than that in group A (P<0.05). The width of the STR was declined with age and presented with significant difference among age groups (P<0.05). No significant difference was observed in the height of the STR in whole age groups (P>0.05). The aeration of the STR was intimately related with age-related morphological changes in the ET. But the important factors influencing the aeration of the STR were not always the same in different age stages. CONCLUSION: The extended length and declined width of the STR with age were mostly related with the prolonging bony part and inwardly bending cartilaginous part of the ET in children and adolescent aged from 0 to 18 years old. In adults aged more than 18 years old, the narrowed caliber of the tympanic orifice of the ET could induce the decline in the width of the STR with age, but unfolded horizontal cartilaginous part of the ET contributed to stable length and height in aeration of the STR.

Anatomical measurement of the ossicles in patients with congenital aural atresia and stenosis.

OBJECTIVES: Our aims were to measure and compare anatomical parameters of the ossicles in normal, congenital aural stenosis (CAS), and congenital aural atresia (CAA) ears. METHODS: This retrospective study was performed using three-dimensional reconstructed images derived from computed tomography scans of 20 normal subjects, 20 CAS patients, and 20 CAA patients. RESULTS: The lengths of the malleus handle and long process of the incus were greater in normal ears than in CAS and CAA ears (all P < 0.05). The angles of the incudostapedial joint and between the short and long processes of the incus were smaller in normal ears than in CAS and CAA ears (all P < 0.05). There were no significant differences in the positions of the malleus head and incudomalleolar joint, the size of the malleus head, the length of the short process of the incus, or the angle of the incudomalleolar joint (P > 0.05). CONCLUSIONS: Anatomical parameters of the lower part, but not of the upper part, of the ossicular chain in CAS and CAA ears differed from those in normal ears. Different branchial arch origins of the upper and lower parts of the ossicular chain may explain these findings. Dysplasia of the second arch, which develops into the lower part of the ossicular chain, may contribute to ossicular malformation in CAA and CAS. Accurate radiographic measurement of malformed ossicles may be useful for reconstructive surgery of CAA and CAS using the patient's native ossicular chain and for choosing an appropriate place for active middle ear implants.

Position of the Internal Aperture of Vestibular Aqueduct in Patients With Enlarged Vestibular Aqueduct.

OBJECTIVE: To investigate the position of the internal aperture of vestibular aqueduct and its relationship to hearing level in patients with enlarged vestibular aqueduct (EVA). METHODS: The size of the common crus and the position of the internal aperture of vestibular aqueduct were compared among control subjects, EVA patients with and without other inner ear malformations. Auditory steady-state response thresholds were compared between EVA patients with different positions of internal apertures. RESULTS: The common crus in EVA patients was shorter than in control subjects (p < 0.05). The internal aperture of the vestibular aqueduct opened solely into the common crus in control subjects, simultaneously into the common crus and vestibule in almost 45% of EVA patients, solely into the common crus, and the vestibule in almost 30 and 25% of EVA patients, respectively. Auditory steady-state response thresholds at 2000 and 4000 Hz were higher in EVA patients whose internal apertures of vestibular aqueducts opened simultaneously into the common crus and vestibule than in those whose internal apertures opened solely into the common crus. CONCLUSION: The common crus is shorter in EVA patients than in control subjects. The internal aperture of the vestibular aqueduct opens solely into the common crus in control subjects. It opens simultaneously into the common crus and vestibule in almost half of the EVA patients. The EVA patients whose internal apertures of vestibular aqueducts open solely into the common crus may have better hearing than those whose internal apertures open simultaneously into the common crus and vestibule.