Cyclopeptide RA-V from Rubia yunnanensis restores activity of Adagrasib against colorectal cancer by reducing the expression of Nrf2.

Adagrasib (MRTX849), an approved and promising KRAS G12C inhibitor, has shown the promising results for treating patients with advanced non-small cell lung cancer (NSCLC) or colorectal cancer (CRC) harboring KRAS-activating mutations. However, emergence of the acquired resistance limits its long-term efficacy and clinical application. Further understanding of the mechanism of the acquired resistance is crucial for developing more new effective therapeutic strategies. Herein, we firstly found a new connection between the acquired resistance to MRTX849 and nuclear factor erythroid 2-related factor 2 (Nrf2). The expression levels of Nrf2 and GLS1 proteins were substantially elevated in different CRC cell lines with the acquired resistance to MRTX849 in comparison with their corresponding parental cell lines. Next, we discovered that RA-V, one of natural cyclopeptides isolated from the roots of Rubia yunnanensis, could restore the response of resistant CRC cells to MRTX849. The results of molecular mechanisms showed that RA-V suppressed Nrf2 protein through the ubiquitin-proteasome-dependent degradation, leading to the induction of oxidative and ER stress, and DNA damage in CRC cell lines. Consequently, RA-V reverses the resistance to MRTX849 by inhibiting the Nrf2/GLS1 axis, which shows the potential for further developing into one of novel adjuvant therapies of MRTX849.

One Case of Drug-Resistant Invasive Fungal Infection after Myelodysplastic Syndrome Chemotherapy.

BACKGROUND: The aim of this study was to evaluate the therapeutic regimen of a patient with myelodysplastic syndrome (MDS) who developed invasive fungal infections caused by drug-resistant Candida tropicalis after chemotherapy and to investigate the effect of drug treatment. METHODS: We referred to the Diagnostic Criteria and Treatment Principles of invasive fungal diseases in patients with hematological diseases and malignant tumors (2013, fourth revised edition) and the Expert Consensus on Clinical Application of Posaconazole (2022 Edition). In addition, the drug treatment regimens of drug-resistant Candida tropicalis were reviewed. The doctors in charge were involved in the drug treatment process, and the ra-tional drug use was selected according to evidence-based medicine. RESULTS: After 4 months of use, the nodules around the body disappeared, and there was no further fever during follow-up. After 6 months of use, posaconazole was discontinued, and the patient continued to follow-up for 1 month without further fever or nodules. CONCLUSIONS: The combination of posaconazole, amphotericin B liposome, and micafungin is effective in the treatment of fluconazole-resistant Candida tropicalis infection.

A Case of Chronic Eosinophilic Leukemia with CSF3R-Mutant Clone and Transformed to Secondary Acute Myeloid Leukemia.

BACKGROUND: Chronic eosinophilic leukemia (CEL) is a rare invasive disease characterized by non-specific cytogenetic abnormalities or elevated mother cells, poor prognosis, and a high risk of conversion to acute leukemia. METHODS: We described the data of a patient with CEL-NOS. RESULTS: This case is a CEL-NOS with four mutations in CSF3R-T618I, DNMT3A Q816, ASXL1, and IDH2. CONCLUSIONS: The patient rapidly evolves into secondary acute myeloid leukemia (AML).

AML with RUNX1::RUNX1T1 Cooperating two Mutations Relapsed Quickly after Achieving CR.

BACKGROUND: Acute myeloid leukemia (AML) with t(8;21)(q22;q22.1); RUNX1::RUNX1T1 has a relatively favorable prognosis with a high complete remission rate and long disease-free survival. METHODS AND RESULTS: Here we describe a patient who had AML with t(8;21)(q22;q22.1); RUNX1::RUNX1T1. Cooperating mutations including KRAS and ASXL1, and with other abnormal karyotype del(17) and with a myelomonocytic differentiation. CONCLUSIONS: The patient relapsed despite achieving a morphologic complete remission (CR).

Machine learning based on magnetic resonance imaging and clinical parameters helps predict mesenchymal-epithelial transition factor expression in oral tongue squamous cell carcinoma: a pilot study.

OBJECTIVES: This study aimed to develop machine learning models to predict phosphorylated mesenchymal-epithelial transition factor (p-MET) expression in oral tongue squamous cell carcinoma (OTSCC) using magnetic resonance imaging (MRI)-derived texture features and clinical features. METHODS: Thirty-four patients with OTSCC were retrospectively collected. Texture features were derived from preoperative MR images, including T2WI, apparent diffusion coefficient mapping, and contrast-enhanced (ce)-T1WI. Dimension reduction was performed consecutively with reproducibility analysis and an information gain algorithm. Five machine learning methods-AdaBoost, logistic regression (LR), naïve Bayes (NB), random forest (RF), and support vector machine (SVM)-were adopted to create models predicting p-MET expression. Their performance was assessed with fivefold cross-validation. RESULTS: In total, 22 and 12 cases showed low and high p-MET expression, respectively. After dimension reduction, 3 texture features (ADC-Minimum, ce-T1WI-Imc2, and ce-T1WI-DependenceVariance) and 2 clinical features (depth of invasion [DOI] and T-stage) were selected with good reproducibility and best correlation with p-MET expression levels. The RF model yielded the best overall performance, correctly classifying p-MET expression status in 87.5% of OTSCCs with an area under the receiver operating characteristic curve of 0.875. CONCLUSION: Differences in p-MET expression in OTSCCs can be noninvasively reflected in MRI-based texture features and clinical parameters. Machine learning can potentially predict biomarker expression levels, such as MET, in patients with OTSCC.

Differentiation of geniculate ganglion venous malformation from schwannoma: dynamic T1-weighted imaging provides unique diagnostic value.

OBJECTIVE: To distinguish geniculate ganglion venous malformation (GGVM) from schwannoma (GGS) by using high-resolution CT (HRCT), routine MRI, and dynamic T1-weighted imaging (T1WI) characteristics. METHODS: Surgically confirmed GGVMs and GGSs between 2016 and 2021 were retrospectively included. Preoperative HRCT, routine MR, and dynamic T1WI were performed on all patients. Clinical data, imaging characteristics including lesion size, involvement of facial nerve (FN), signal intensity, enhancement pattern on dynamic T1WI, and bone destruction on HRCT were evaluated. Logistic regression model was developed to identify independent factors for GGVMs, and the diagnostic performance was accessed by receiving operative curve (ROC) analysis. Histological characteristics were explored for both GGVMs and GGSs. RESULTS: Twenty GGVMs and 23 GGSs with mean age of 31 were included. On dynamic T1WI, 18 GGVMs (18/20) showed "pattern A" enhancement (a progressive filling enhancement), while all 23 GGSs showed "pattern B" enhancement (a gradual whole-lesion enhancement) (p < 0.001). Thirteen GGVMs (13/20) showed the "honeycomb" sign whereas all GGS (23/23) showed extensive bone changes on HRCT (p < 0.001). Lesion size, involvement of FN segment, signal intensity on non-contrast T1WI and T2-weighted imaging (T2WI), and homogeneity on enhanced T1WI were obviously differed between two lesions (p < 0.001, p = 0.002, p < 0.001, p = 0.01, p = 0.02, respectively). Regression model showed the "honeycomb" sign and "pattern A" enhancement were independent risk factors. Histologically, GGVM was characterized by interwoven dilated and tortuous veins, while GGS was characterized by abundant spindle cells with dense arterioles or capillaries. CONCLUSIONS: The "honeycomb" sign on HRCT and "pattern A" enhancement on dynamic T1WI are the most promising imaging characteristics for differentiating GGVM from GGS. CLINICAL RELEVANCE STATEMENT: The characteristic sign and enhancement pattern on HRCT and dynamic T1-weighted imaging allow preoperative differentiation of geniculate ganglion venous malformation and schwannoma feasible, which will improve clinical management and benefit patient prognosis. KEY POINTS: • The "honeycomb" sign on HRCT is a reliable finding to differentiate GGVM from GGS. • GGVM typically shows "pattern A" enhancement (focal enhancement of the tumor on early dynamic T1WI, followed by progressive contrast filling of the tumor in the delayed phase), while "pattern B" enhancement (gradual heterogeneous or homogeneous enhancement of the whole lesion) is observed in GGS on dynamic T1WI.

A preliminary study of diffusion tensor imaging in root entry zone of primary trigeminal neuralgia.

Objective: Primary Trigeminal Neuralgia (PTN) is a common and refractory neurological disease. Conventional vascular compression theory could not completely explain the etiology and pathogenesis of PTN. This study used diffusion tensor imaging (DTI) to demonstrate the microstructural changes of root entry zone (REZ) region in PTN patients. Materials and methods: DTI sequences was performed on PTN patients and healthy controls (HCs). Clinical data included affected side, disease course and visual analogue scale (VAS) were collected. Quantitative DTI variables such as FA, MD, AD and RD of the root entry/Exit zone (REZ) were measured and compared in PTN/HCs, affected/unaffected side, and pre/post operation groups. The PCoA was established to conduct overall differences between PTN group and the HCs. Results: A total of 17 patients with PTN (mean age 59.29 ± 8.53; 5 men) and 34 HCs (mean age 57.70 ± 6.37; 10 men) were included. Lower FA value of the affected side of PTN group was observed compared to the unaffected side and the HCs (p = 0.001), whereas the values of MD, AD and RD were significantly increased (p < 0.001). Moreover, the decrease of FA value was recovered post operation. PCoA results of the comprehensive indexes can significantly distinguish PTN group from HCs (r = 0.500, p < 0.001). Conclusion: Quantitative variables derived from DTI in REZ had significantly different profiles between PTN patients and HCs, which were associated with VAS situation and the disease course of PTN. The comprehensive index established on DTI variables were of great potential to reveal the microstructure changes in PTN patients and predict the therapeutic effect.

Edge-enriched MoS2 nanosheets modified porous nanosheet-assembled hierarchical In2O3 microflowers for room temperature detection of NO2 with ultrahigh sensitivity and selectivity.

Nitrogen dioxide (NO2) is one of the most hazardous toxic pollutants to human health and the environment. However, deficiencies of low sensitivity and poor selectivity at room temperature (RT) restrain the application of NO2 sensors. Herein, the edge-enriched MoS2 nanosheets modified porous nanosheets-assembled three-dimensional (3D) In2O3 microflowers have been synthesized to improve the sensitivity and selectivity of NO2 detection at RT. The results show that the In2O3/MoS2 composite sensor exhibits a response as high as 343.09-5 ppm NO2, which is 309 and 72.5 times higher than the sensors based on the pristine MoS2 and In2O3. The composite sensor also shows short recovery time (37 s), excellent repeatability and long-term stability. Furthermore, the response of the In2O3/MoS2 sensor to NO2 is at least 30 times higher than that of other gases, proving the ultrahigh selectivity of the sensor. The outstanding sensing performance of the In2O3/MoS2 sensor can be attributed to the synergistic effect and abundant active sites originating from the p-n heterojunction, exposed edge structures and the designed 2D/3D hybrid structure. The strategy proposed herein is expected to provide a useful reference for the development of high-performance RT NO2 sensors.

A drug-free nanozyme for mitigating oxidative stress and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an incurable disease of the gastrointestinal tract with a lack of effective therapeutic strategies. The proinflammatory microenvironment plays a significant role in both amplifying and sustaining inflammation during IBD progression. Herein, biocompatible drug-free ceria nanoparticles (CeNP-PEG) with regenerable scavenging activities against multiple reactive oxygen species (ROS) were developed. CeNP-PEG exerted therapeutic effect in dextran sulfate sodium (DSS)-induced colitis murine model, evidenced by corrected the disease activity index, restrained colon length shortening, improved intestinal permeability and restored the colonic epithelium disruption. CeNP-PEG ameliorated the proinflammatory microenvironment by persistently scavenging ROS, down-regulating the levels of multiple proinflammatory cytokines, restraining the proinflammatory profile of macrophages and Th1/Th17 response. The underlying mechanism may involve restraining the co-activation of NF-κB and JAK2/STAT3 pathways. In summary, this work demonstrates an effective strategy for IBD treatment by ameliorating the self-perpetuating proinflammatory microenvironment, which offers a new avenue in the treatment of inflammation-related diseases.

Genetic findings of Sanger and nanopore single-molecule sequencing in patients with X-linked hearing loss and incomplete partition type III.

BACKGROUND: POU3F4 is the causative gene for X-linked deafness-2 (DFNX2), characterized by incomplete partition type III (IP-III) malformation of the inner ear. The purpose of this study was to investigate the clinical characteristics and molecular findings in IP-III patients by Sanger or nanopore single-molecule sequencing. METHODS: Diagnosis of IP-III was mainly based on clinical characteristics including radiological and audiological findings. Sanger sequencing of POU3F4 was carried out for these IP-III patients. For those patients with negative results for POU3F4 Sanger sequencing, nanopore long-read single-molecule sequencing was used to identify the possible pathogenic variants. Hearing intervention outcomes of hearing aids (HAs) fitting and cochlear implantation (CI) were also analyzed. Aided pure tone average (PTA) was further compared between two groups of patients according to their different locations of POU3F4 variants: in the exon region or in the upstream region. RESULTS: In total, 18 male patients from 14 unrelated families were diagnosed with IP-III. 10 variants were identified in POU3F4 by Sanger sequencing and 6 of these were reported for the first time (p.Gln181*, p.Val215Gly, p.Arg282Gln, p.Gln316*, c.903_912 delins TGCCA and p.Arg205del). Four different deletions that varied from 80 to 486 kb were identified 876-1503 kb upstream of POU3F4 by nanopore long-read single-molecule sequencing. De novo genetic mutations occurred in 21.4% (3/14) of patients with POU3F4 mutations. Among these 18 patients, 7 had bilateral HAs and 10 patients received unilateral CI. The mean aided PTA for HAs and CI users were 41.1 ± 5.18 and 40.3 ± 7.59 dB HL respectively. The mean PTAs for patients with the variants located in the exon and upstream regions were 39.6 ± 6.31 versus 43.0 ± 7.10 dB HL, which presented no significant difference (p = 0.342). CONCLUSIONS: Among 14 unrelated IP-III patients, 28.6% (4/14) had no definite mutation in exon region of POU3F4. However, possible pathogenic deletions were identified in upstream region of this gene. De novo genetic mutations occurred in 21.4% (3/14) of patients with POU3F4 mutation. There was no significant difference of hearing intervention outcomes between the IP-III patients with variants located in the exon region and in the upstream region.

Circ_0009910 sponges miR-491-5p to promote acute myeloid leukemia progression through modulating B4GALT5 expression and PI3K/AKT signaling pathway.

BACKGROUND: Acute myeloid leukemia (AML) is a heterogeneous group of leukemias with an overall poor prognosis. Circular RNAs (circRNAs) have been verified to play important regulatory roles in AML progression. However, the role and molecular mechanism of circ_0009910 in AML development have not be completely clarified. METHODS: The expression levels of circ_0009910, microRNA-491-5p (miR-491-5p), and ß-1, 4-galactosyltransferase 5 (B4GALT5) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. Cell proliferation and self-renewal ability were assessed via Cell Counting Kit-8 (CCK-8) and sphere formation assay. Cell cycle distribution and cell apoptosis were evaluated by flow cytometry. Caspase-3 activity was tested by Caspase-3 Activity Assay Kit. Western blot was used to examine the protein levels of autophagy-related markers and PI3K/AKT pathway-related markers. The interaction between miR-491-5p and circ_0009910 or B4GALT5 was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, or RNA pull-down assay. RESULTS: Circ_0009910 was highly expressed in AML tissues and cells. Silenced circ_0009910 could significantly inhibit the proliferation, sphere formation, and autophagy and promoted the apoptosis of AML cells. Circ_0009910 bound to miR-491-5p in AML cells, and circ_0009910 promoted AML progression partly through sponging miR-491-5p in vitro. B4GALT5 was a target of miR-491-5p, and miR-491-5p overexpression-mediated influences in AML cells were effectually overturned by the addition of B4GALT5 overexpression plasmid. Furthermore, circ_0009910 could regulate the expression of B4GALT5 by downregulating miR-491-5p in AML cells. Additionally, circ_0009910 could activate the PI3K/AKT signaling pathway by sponging miR-491-5p. CONCLUSION: Circ_0009910 could suppress the proliferation, sphere formation, and autophagy and accelerated apoptosis by modulating B4GALT5 expression and activating the PI3K/AKT signaling pathway via sponging miR-491-5p in AML cells, suggesting that circ_0009910 might be a potential biomarker for the treatment of AML.

Determination of Cervical Lymph Nodes Metastasis and Extra Nodal Extension Status by Quantitative Assessment of Border Irregularity and Apparent Diffusion Coefficient in Patients With Tongue Squamous Cell Carcinoma.

OBJECTIVE: The objective of this study was to determine the diagnostic value of quantitative border irregularity assessment and apparent diffusion coefficient (ADC) in patients with squamous cell carcinoma of the tongue (SCCT). METHODS: Cervical lymph nodes (n = 192) from 63 patients with SCCT were examined preoperatively by magnetic resonance imaging, including routine head and neck sequences, dynamic contrast-enhanced magnetic resonance imaging, diffusion-weighted imaging, ADC, surface regularity (SR), and visually assessed variables, and evaluated pathologically after surgery. RESULTS: Necrosis, lymphatic hilum, unclear margin, higher SR, long to short axis ratio, and ADC were associated with metastasis in cervical lymph nodes (M-cLNs) and extranodal extension (ENE), and thickened nodal rim with ENE alone. Apparent diffusion coefficient, SR, unclear margin, and visible necrosis were strongly associated with M-cLN, whereas SR, unclear margin, and visible necrosis were associated with ENE status on logistic regression analysis. CONCLUSIONS: Quantitative SR and ADC data greatly improved diagnosis of M-cLNs and ENE, relative to visible variables alone in patients with SCCT.

Cochlear Duct Length Calculation: Comparison Between Using Otoplan and Curved Multiplanar Reconstruction in Nonmalformed Cochlea.

OBJECTIVE: To describe a new method to measure the cochlear parameters using Otoplan software, and to compare it with the traditional method using curved multiplanar reconstruction (cMPR). STUDY DESIGN: Retrospective analysis using internal consistency reliability and paired sample t test. SETTING: Tertiary referral center. PATIENTS: Thirty-four patients including 68 ears from a clinical trial were retrospectively reviewed. MAIN OUTCOME MEASURES: The length, width, height (distances A, B, H), and cochlear duct length of each cochlea were measured independently using two modalities: Otoplan and cMPR. Internal consistency reliability of the two modalities was analyzed. The time spent on each measurement was also recorded. RESULTS: Otoplan software was compatible with all radiological data in this series. Distances A, B, and H showed no significant differences between Otoplan (9.33 ±â€Š0.365, 6.61 ±â€Š0.359, and 2.91 ±â€Š0.312 mm) and cMPR (9.32 ±â€Š0.314, 6.59 ±â€Š0.342, and 2.93 ±â€Š0.250 mm). The average cochlear duct length calculated by Otoplan was 34.37 ±â€Š1.481 mm, which was not significantly different from that calculated by cMPR (34.55 ±â€Š1.903mm, p = 0.215). The measurements with Otoplan had better internal consistency reliability compared with those by cMPR, and measurements with a higher peak kilovoltage (140 kVp) CT scan showed further higher internal consistency reliability. Time spent on each cochlea by Otoplan was 5.9 ±â€Š0.69 min, significantly shorter than that by cMPR (9.3 ±â€Š0.72 min). CONCLUSION: Otoplan provides more rapid and reliable measurement of the cochlea than cMPR. Furthermore, it can be easily used in the laptop computer.

Intact wayfinding abilities in patients with Parkinson's disease.

INTRODUCTION: Previous studies have found that patients with Parkinson's Disease (PD) showed impairments in certain aspects of spatial orientation. The current study aimed to systematically investigate whether these impairments extend to wayfinding abilities in patients with PD. Wayfinding refers to the ability to navigate to an unseen location in the environment and is essential to one's everyday functioning. METHODS: A total of 24 patients with PD, 20 ability matched controls, 21 college students participated in a series of experimental behavioral tasks and a self-report of environmental abilities. In the route learning task, participants learned and then recalled routes. In the survey learning task, participants were asked to form configurational or survey knowledge. In the map tracing tack, participants were asked to trace the turning directions of a route on a map. RESULTS: Patients with PD showed no impairments in the behavioral measures of wayfinding relative to ability matched controls. Both groups performed worse than college students, who had higher cognitive levels. Patients with PD, however, reported a higher competency in environmental abilities than college students. CONCLUSION: Although wayfinding abilities may decrease as cognitive abilities decline, they do not appear as a unique impairment for patients with PD relative to their cognitive level.

Image-guided surgery of head and neck carcinoma in rabbit models by intra-operatively defining tumour-infiltrated margins and metastatic lymph nodes.

BACKGROUND: The infiltrative nature and lymphatic metastasis of head and neck squamous cell carcinoma (HNSCC) are the main reasons leading to its poor prognosis. METHODS: A multimodal surface-enhanced resonance Raman spectroscopy (SERRS) and magnetic resonance (MR) nanoprobe, in which paramagnetic chelators and heptamethine cyanine-based Raman reporter molecules were functionalized on a gold nanostar (AuS) surface was developed. Preoperative MRI and intraoperative SERRS-guided surgery were performed on rabbits bearing head and neck VX2 tumours to determine feasibility of the MR/SERRS probe in defining tumour marginal infiltration and lymph nodes metastasis. FINDINGS: Preoperative T1-weighted MRI (T1W-MRI) unambiguously delineated the orthotopic head and neck VX2 tumour xenograft and detected the metastatic lymph nodes in rabbit models after intravenous administration of the probe. With the assistance of a hand-held Raman detector, the probe not only intra-operatively demarcated invasive tumour margins but also successfully distinguished metastatic lymph nodes via a remarkable attenuated Raman signal. Importantly, the group of rabbits subjected to the SERRS-guided surgery exhibited prolonged median survival time (78 days) compared with that of the control group without surgical intervention (29 days) or the group treated with conventional white-light-guided surgery (42 days) (P < 0.0001). INTERPRETATION: we developed a novel AuS-based multimodal MR/SERRS probe. The capability of this probe to identify both a tumour xenograft and metastatic lymph nodes preoperatively by MRI and intra-operatively by SERRS not only avoids the need for unnecessary resection of neurological structures but also provides a new opportunity to improve the surgical prognosis of head and neck carcinoma of infiltrative nature.

Multi-parametric effect in predicting tumor histological grade by using susceptibility weighted magnetic resonance imaging in tongue squamous cell carcinoma.

BACKGROUND: Susceptibility weighted imaging (SWI) is helpful for depicting hemorrhage, calcification, and increased vascularity in some neoplasms, which may reflect tumor grade. In this study, we aimed to apply SWI in patients with oral tongue squamous cell carcinomas (OTSCCs) and relate multi-parametric effect to tumor histological grade prediction. METHODS: Preoperative MR examinations were performed on a 1 .5T MRI scanner with T1-, T2- and contrast-enhanced (CE) T1-weighted imaging. In addition to routine head and neck MRI sequences, SWI was performed. Tumor thickness and volume were measured. Intratumoral susceptibility signal intensities (ITSSs), ITSS score and ITSS ratio on SWI were evaluated and recorded. Subjects were sub-grouped into low- and high-grade according to the histological findings post operation. Parameters such as tumor thickness, tumor volume and three ITSS related parameters were compared between low- and high-grade groups. ROC analysis was performed on above parameters to access the capability in predicting tumor histological grade. Different multi-parametric models were run to access multi-parametric combination effect. RESULTS: Thirty patients with OTSCC were finally included in the study. Twenty of them were categorized as low-grade SCC and the other ten subjects were high-grade SCC according to the pathologic findings. No significant difference was seen for tumor thickness or tumor volume between two sub-groups. ITSSs were seen in 23/30 patients. Significant difference of ITSS scores between low- and high-grade OTSCCs was observed, with mean value of 0.95 ± 0.83 and 1.70 ± 0.95, respectively. Univariate ROC analysis demonstrated ITSSs, ITSS score and ITSS ratio were valuable parameters for predicting tumor histological grade and ITSSs was superior to the other two parameters, with an area under ROC curve of 0.790. Multi-parametric model using combination of ITSSs and tumor thickness would greatly improve the predictive capability in comparison with a univariate approach, yielding the area under ROC curve of 0.84(0.69,0.99). On contrast-enhanced SWI (CE-SWI), ITSSs were shown more clearly delineated in comparison with non-contrast enhanced SWI. CONCLUSIONS: In conclusion, SWI was superior in depiction of internal characteristics of OTSCCs, which would potentially provide more diagnostic information. Multi-parametric model using combination of ITSSs and tumor thickness would be valuable in predicting tumor histological grade.

Predictors of round window membrane visibility in pediatric cochlear implant surgery using temporal bone HRCT: A retrospective study.

OBJECTIVE: To predict round window membrane (RWM) visibility and electrode insertion sites using high-resolution computed tomography (HRCT) in pediatric cochlear implant surgery. MATERIALS AND METHODS: Sixty-two ears of 36 infants less than 1 year old were included in our study. Intraoperative RWM visibility was classified into three types corresponding to three different surgical approaches. Radiologic parameters were measured on preoperative axial temporal HRCT images and correlated with RWM visibility and surgical approaches. RESULTS: A significant correlation was found between the degree of RWM visibility and the following two parameters: 1) a line (lw) was drawn from the posterior margin of the RWM to the intersection point of the posterior wall of the external auditory canal (EAC) and mastoid cortex. Another line (lf) was drawn between the posterior margin of the RWM and the lateral margin of the FN. The angle between lw and lf was measured as angle A, P < 0.01, R2 = -0.809; 2) a line (lm) was drawn from the anterior to posterior margin of the RWM, and the angle between lm and lf was measured as angle B, P < 0.01, R2 = -0.850. A nonsignificant correlation was found between the degree of RWM visibility and the facial recess width, p > 0.05, R2 = -0.00015. CONCLUSION: RWM visibility showed a high correlation with the two angular measurements (angle A and angle B) and was associated with electrode insertion sites. In children less than one year old, surgeons can depend on those two parameters in predicting the RWM visibility.

TLR4 mediates upregulation and sensitization of TRPV1 in primary afferent neurons in 2,4,6-trinitrobenzene sulfate-induced colitis.

Elevated excitability of primary afferent neurons underlies chronic pain in patients with functional or inflammatory bowel diseases. Recent studies have established an essential role for an enhanced transient receptor potential vanilloid subtype 1 (TRPV1) signaling in mediating peripheral hyperalgesia in inflammatory conditions. Since colocalization of Toll-like receptor 4 (TLR4) and TRPV1 has been observed in primary afferents including the trigeminal sensory neurons and the dorsal root ganglion neurons, we test the hypothesis that TLR4 might regulate the expression and function of TRPV1 in primary afferent neurons in 2,4,6-trinitrobenzene sulfate (TNBS)-induced colitis using the TLR4-deficient and the wild-type C57 mice. Despite having a higher disease activity index following administration of 2,4,6-trinitrobenzene sulfate, the TLR4-deficient mice showed less inflammatory infiltration in the colon than the wild-type mice. Increased expression of TLR4 and TRPV1 as well as increased density of capsaicin-induced TRPV1 current was observed in L4-S2 dorsal root ganglion neurons of the wild-type colitis mice till two weeks post 2,4,6-trinitrobenzene sulfate treatment. In comparison, the TLR4-deficient colitis mice had lower TRPV1 expression and TRPV1 current density in dorsal root ganglion neurons with lower abdominal withdrawal response scores during noxious colonic distensions. In the wild type but not in the TLR4-deficient dorsal root ganglion neurons, acute administration of the TLR4 agonist lipopolysaccharide increased the capsaicin-evoked TRPV1 current. In addition, we found that the canonical signaling downstream of TLR4 was activated in 2,4,6-trinitrobenzene sulfate-induced colitis in the wild type but not in the TLR4-deficient mice. These results indicate that TLR4 may play a major role in regulation of TRPV1 signaling and peripheral hyperalgesia in inflammatory conditions.