Single-port robotic-assisted laparoscopic synchronous surgery in pediatric patent processus vaginalis.

PURPOSE: Patent processus vaginalis (PPV) is usually observed in pediatric abdominal surgery; however, robotic single-port surgery in repairing processus vaginalis has not been reported in children. Herein, we present our clinical experiences in single-port robotic surgeries for PPV repair to evaluate both efficacy and safety. METHODS: Retrospective analysis of patients underwent single-port robotic-assisted laparoscopic surgery for genitourinary diseases from May 2020 and May 2023 in our center. Among these patients, 21 children had PPV repaired at the same time. The case characteristics and follow-up data were recorded. RESULTS: Twenty-one of the 53 children were found to have PPV during genitourinary surgery. The simultaneous treatment of the primary disease and PPV with a single-port robotic-assisted platform was both convenient and safe. There was no significant increase in total operation time, and no excessive intraoperative hemorrhage was observed in any of the operations. There were no complications observed on follow-up. CONCLUSION: With a high incidence of PPV in children, a single-port robotic-assisted procedure is feasible and effective if simultaneously performed when addressing a primary abdominal disease.

Characteristics of endoplasmic reticulum stress in colorectal cancer for predicting prognosis and developing treatment options.

BACKGROUND: An increasing body of evidence supports an essential role for endoplasmic reticulum stress (ERS) in colorectal cancer (CRC). In this study, we developed an ERS-related genes (ERSRGs) model to aid in the prognostic evaluation and treatment of CRC patients. METHODS: The training set and validation set data were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. ERSRGs were obtained from the GeneCards database. A prognostic risk scoring model was constructed using the least absolute shrinkage and selection operator (LASSO) along with univariate Cox regression analysis. To further predict the probability of survival for patients at 1, 2, and 3 years, a nomogram was devised. The advantages of the prognostic risk score model in screening patients' sensitive to chemotherapy and immunotherapy were analyzed by drug sensitivity analysis and immune correlation analysis. Finally, hub genes associated with poor prognosis in the risk model were screened by Protein-protein interaction (PPI) network and their expression was validated using clinical specimens. RESULTS: A risk model for overall survival (OS) was developed using 16 ERSRGs associated with prognosis. Through analyses, we demonstrated a high degree of reliability for the prognostic risk scoring model. The constructed nomograms performed well in predicting patient survival over 1, 3, and 5 years. The calibration curve and decision curve analysis (DCA) supported a high degree of accuracy for the model. Patients in the low-risk group had a lower IC50 for the common chemotherapy drug, 5-FU, and responded better to immunotherapy. hub poor prognostic genes were validated in CRC clinical specimens. CONCLUSION: We have identified and validated a new ERS prognostic marker that can accurately predict the survival status of CRC patients for clinicians and better provide personalized treatment plans.

Abnormal lower expression of GPR183 in peripheral blood T and B cell subsets of systemic lupus erythematosus patients.

G protein-coupled receptor 183 (GPR183) has been indicated to mediate the migration and localisation of immune cells in T cell-dependent antibody responses. Systemic lupus erythematosus (SLE) is a canonical autoimmune disease involving B cell-mediated tolerance destruction and excessive pathogenic autoantibody production, in which multiple GPCRs play a role. To date, there has been no systematic study regarding the expression of GPR183 in lymphocyte subsets of SLE patients. In this research, firstly, we observed the expression trends of GRP183 in various T and B cell subsets in human tonsil tissues. These lymphocyte subsets include CD4+, CD8+, naïve T, effector T, Tfh, activated Tfh, Th1, Th2, Th17, Treg, CD19+CD27-, CD19+CD27+, naïve B, germinal centre B, memory B, and plasma cells. Further, compared with healthy controls (HCs), GPR183 expression levels in above peripheral blood lymphocyte subsets of patients with SLE were reduced overall. The differential expression of GPR183 expression between inactive and active SLE patients indicates that GPR183 expression may be concerned with the disease activity of SLE. This was further confirmed through the strong negative correlation with SLEDAI score and positive correlation with serum complement protein C3, C4 and C1q levels. Further receiver operating characteristic (ROC) curve analysis revealed that GPR183 expression in circulating CD27-IgD+ B cells may be beneficial in distinguishing between inactive and active SLE patients. In addition, type I interferon stimulation could down-regulate the expression of GPR183 in peripheral blood T and B cell subsets. Aberrant expression of GPR183 may provide some novel insights into disease activity prediction and underlying pathogenesis of SLE.

The IL-21-TET2-AIM2-c-MAF pathway drives the T follicular helper cell response in lupus-like disease.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that involves T follicular helper (TFH ) cell-mediated humoral immune responses. Absent in melanoma 2 (human AIM2 and murine Aim2) is a well-known component of the inflammasome in the innate immune system. Surprisingly, we observed that in SLE patients, upregulated levels of AIM2 expression were found in peripheral blood and skin lesions, with the highest levels detected in TFH -like cells. In the CD4cre Aim2fl/fl conditional knockout mice, a markedly reduced TFH cell response was observed, with significantly lower levels of serum autoantibodies and proteinuria, as well as profoundly reduced renal IgG deposition in pristane-induced lupus mice. Mechanistically, IL-21 was found to recruit hydroxymethyltransferase ten-eleven translocation 2 (TET2) to the AIM2 promoter, resulting in DNA demethylation and increased transcription of AIM2. In addition, AIM2 could regulate c-MAF expression to enhance IL-21 production, which consequently promoted TFH cell differentiation. Our results have identified a role of AIM2 in promoting the TFH cell response and further revealed that the IL-21-TET2-AIM2-c-MAF signalling pathway is dysregulated in lupus pathogenesis, which provides a potential therapeutic target for SLE.

Evolution of Electronic Structure in Pristine and Rb-Reconstructed Surfaces of Kagome Metal RbV3Sb5.

We report on in situ low-temperature (4 K) scanning tunneling microscope measurements of atomic and electronic structures of the cleaved surfaces of an alkali-based kagome metal RbV3Sb5 single crystals. We find that the dominant pristine surface exhibits Rb-1×1 structure, in which a unique unidirectional √3a0 charge order is discovered. As the sample temperature slightly rises, Rb-√3×1 and Rb-√3×√3 reconstructions form due to desorption of surface Rb atoms. Our conductance mapping results demonstrate that Rb desorption not only gives rise to hole doping but also reconstructs the electronic band structures. Surprisingly, we find a ubiquitous gap opening near the Fermi level in tunneling spectra on all the surfaces despite their large differences of hole-carrier concentration, indicating an orbital-selective band reconstruction in RbV3Sb5. The Rb desorption induced electronic reconstructions are further confirmed by our density functional theory calculations.

AIM2 deficiency in B cells ameliorates systemic lupus erythematosus by regulating Blimp-1-Bcl-6 axis-mediated B-cell differentiation.

Absent in melanoma 2 (AIM2) has been reported to be a component of inflammasomes in innate immune cells. Surprisingly, AIM2 is expressed by B cells, and higher AIM2 expression is observed in the B cells from lupus patients. To date, the inflammasome-independent function of AIM2 in B cells remains unclear. Here, we report increased expression of AIM2 in human tonsil memory and germinal center (GC) B cells and in memory B cells and plasma cells from the circulation and skin lesions of lupus patients. Conditional knockout of AIM2 in B cells reduces the CD19+ B-cell frequency in lymph nodes and spleens, and dampens KLH-induced IgG1-antibody production. In a pristane-induced mouse model of lupus, AIM2 deficiency in B cells attenuates lupus symptoms and reduces the frequency of GC B cells, T follicular helper (Tfh) cells, plasmablast cells, and plasma cells. Furthermore, the loss of AIM2 in human B cells leads to the increased expression of Blimp-1 and reduces the expression of Bcl-6. However, the silencing of Blimp-1 and Bcl-6 has no significant effect on AIM2 expression, indicating that AIM2 might be the upstream regulator for Blimp-1 and Bcl-6. In addition, IL-10 is found to upregulate AIM2 expression via DNA demethylation. Together, our findings reveal that AIM2 is highly expressed in the B cells of lupus patients and promotes B-cell differentiation by modulating the Bcl-6-Blimp-1 axis, providing a novel target for SLE treatment.

An Enhanced Expression Level of CXCR3 on Tfh-like Cells from Lupus Skin Lesions Rather Than Lupus Peripheral Blood.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, and the etiopathogenesis is unclear. Follicular helper T (Tfh) cells have been reported as an important pathogenic cell type in SLE. CXCR3 was reported to be decreased on lupus peripheral CD4+T cells. However, the expression level of CCR4, CCR6 and CXCR3 on Tfh-like cells in SLE peripheral blood and skin lesions is unknown. In this study, we detected CCR4, CCR6 and CXCR3 expression level on Tfh-like cells in the peripheral blood and skin lesions from SLE patients and normal controls (NCs). A decreased expression level of CXCR3 on Tfh-like cells was found in lupus peripheral blood. However, an increased CXCR3 expression was observed on total CD4+T and Tfh-like cells from lupus skin lesions. Moreover, we observed a higher expression level of CXCR3 in Tfh cells from human tonsils. These findings indicate that CXCR3 might help Tfh-like cells to migrate into the inflammatory sites.

Adoptive Cellular Gene Therapy for the Treatment of Experimental Autoimmune Polychondritis Ear Disease.

In the past, the clinical therapy for autoimmune diseases, such as autoimmune polychondritis ear disease, was mostly limited to nonspecific immunosuppressive agents, which could lead to variable responses. Currently, gene therapy aims at achieving higher specificity and less adverse effects. This concept utilizes the adoptive transfer of autologous T cells that have been retrovirally transduced ex vivo to express and deliver immunoregulatory gene products to sites of autoimmune inflammation. In the animal model of collagen-induced autoimmune polychondritis ear disease (CIAPED), the adoptive transfer of IL-12p40-expressing collagen type II (CII)-specific CD4+ T-cell hybridomas resulted in a significantly lower disease incidence and severity compared with untreated or vector-only-treated animals. In vivo cell detection using bioluminescent labels showed that transferred CII-reactive T-cell hybridomas accumulated in the inflamed earlobes of the mice with CIAPED. In vitro analysis demonstrated that IL-12p40-transduced T cells did not affect antigen-specific T-cell activation or systemic anti-CII Ab responses. However, IL-12p40-transduced T cells suppressed IFN-γ and augmented IL-4 production, indicating their potential to act therapeutically by interrupting Th1-mediated inflammatory responses via augmenting Th2 responses. These results indicate that the local delivery of IL-12p40 by T cells could inhibit CIAPED by suppressing autoimmune responses at the site of inflammation.

[Expressions of LL-37 and IL-8 in chronic sinusitis with nasal polyps].

OBJECTIVE: To investigate the expressions of LL-37 and IL-8 in chronic sinusitis with nasal polyps. METHOD: Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining were used to detect the expressions of LL-37 and IL-8 in nasal polyp tissues of 31 patients with chronic sinusitis and inferior turbinate tissues of 11 patients with chronic rhinitis. RESULT: LL-37 and IL-8 mRNA were all positively expressed in all nasal polyps and inferior turbinate tissues. There were significant increases of LL-37 and IL-8 mRNA expressions in nasal polyps compared with the inferior turbinate tissues (P < 0.01). There were also significant increases of positive expression rates of LL-37 and IL-8 protein in nasal polyps, compared with the inferior turbinate tissues (P < 0.01). There was a positive relationship between the mRNA and protein expressions of LL37 and IL-8 (P < 0.01). CONCLUSION: The expressions of LL-37 and IL-8 in nasal polyps suggest that they may play a role in the pathogenesis of chronic sinusitis. Besides its innate immune, LL-37 could enhance human body's anti-infected function by increasing acquired immune.

[Prevention and management of blindness following endonasal sinus surgery].

OBJECTIVE: To explore the causes and the management of serious eye complications occurring in the endoscopic sinus surgery. METHOD: Three patients of chronic sinusitis and nasal polyps suffered with blindness in endoscopic sinus surgery and in nasal packing with iodoform and petrolatum gauze were treated. RESULT: Orbital wall and structure were injured in 2 cases during endoscopic sinus surgery, among which, 1 case blinded with deformation of the eyeball during operation underwent optic nerve exploration and orbital muscle reparation immediately. One case developed periocular swelling, eyelid hematoma, conjunctiva edema and blinded 2 days later, and was treated with hematoma clearance and optic nerve decompression. Another 1 case blinded immediately after ethmoid packing, and vision recovered after nasal pack removed. Antibiotics, corticosteroid and nerve growth factor were administered for 4 weeks in all patients. After 6-month follow-up, 1 case was blinded with eyeball atrophy, 1 case was only photonasty, another regained normal vision. CONCLUSION: The causes of blindness in endoscopic sinus surgery are directly related to orbital structure trauma and orbital hematoma. The optic nerve during operation should be protected carefully, if ethmoid sinus over development is demonstrated by CT scan. The application of gauze should be avoided when the medial orbital wall is injured. Decompression of optic nerve should be performed as early as possible, if vision damaged.

Impaired stria vascularis in the inner ear of apolipoprotein E gene knockout mice.

PURPOSE: To study apoptotic cell death, the expression of endothelial nitric oxide synthase (eNOS) and the capillary density in the cochleae of apolipoprotein E gene knockout (ApoE KO) mice. METHODS: Cochleae of ApoE KO mice were stained by HE, anti-caspase-3 and anti-eNOS antibodies and TUNEL (in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling). Capillary density was measured in the stria vascularis and in the modiolus. RESULTS: Apoptotic cell death was found in the stria vascularis of ApoE KO mice, but not in the organ of Corti. The expression of eNOS and the capillary density were decreased in the stria vascularis and in the modiolus of ApoE KO mice. CONCLUSION: These results suggest that cells in the inner ear of ApoE KO mice take different pathways to undergo cell death, and apoptotic cell death is only involved in the stria vascularis. These pathological changes may play a role in the hearing loss that has been found in ApoE KO mice.

[Diagnosis and management of lipogranuloma of the eyelids from nasal endoscopic surgery].

OBJECTIVE: To enhance the safety of nasal endoscopic surgery and decrease its complications of eyes. METHOD: Three patients of chronic rhinosinusitis and nasal polyposis with lipogranulomas of the eyelids after nasal endoscopic surgery and nasal packing of petrolatum gauze were reported and analyzed, and their treatment results were presented during the last 2 years. RESULT: The medial orbital wall injury occurred in all three patients during endoscopic sinus surgery. The patients developed an ipsilateral periocular swelling, eyelid hematoma and palpebral conjunctival edema during 2 to 3 hours after surgery. Nasal packs petrolatum gauze were removed 10-24 hours after surgery. The patients were discharged from hospital when periorbital swelling and eyelid ecchymoma disappeared, and nasal cavity obstruction was improved 6 to 8 days after surgery. The swelling and nodular mass of ipsilateral eyelids (one in left upper eyelid and two in right lower eyelid) were found 12-15 days after surgery, and their eye movement and eyesight were normal. Antibiotic and corticosteroid were administered for 3 4 weeks with only improvement in eyelid swelling. These masses of eyelids were completely excised through palpebral margin 1-6 months after surgery. The histopathological examination of the surgical specimens showed lipogranuloma. No recurrence and symptom of the eyes had been observed during 4-18 months follow up. CONCLUSION: The lipogranuloma of the eyelid is a rare and late complication after nasal endoscopic surgery and nasal packing with vaspetrolatum gauze. The medial orbital wall injury and bleeding during surgery, and vaseline of nasal packing permeated into the eyelid are the direct causes of this complication. The application of petrolatum gauze should be avoided when the medial orbital wall trauma is identified. The complete excision of granulomas is a best effective therapy.

Identification of 17 hearing impaired mouse strains in the TMGC ENU-mutagenesis screen.

The Tennessee Mouse Genome Consortium (TMGC) employed an N-ethyl-N-nitrosourea (ENU)-mutagenesis scheme to identify mouse recessive mutants with hearing phenotypes. We employed auditory brainstem responses (ABR) to click and 8, 16, and 32 kHz stimuli and screened 285 pedigrees (1819 mice of 8-11 weeks old in various mixed genetic backgrounds) each bred to carry a homozygous ENU-induced mutation. To define mutant pedigrees, we measured > or = 12 mice per pedigree in > or = 2 generations and used a criterion where the mean ABR threshold per pedigree was two standard deviations above the mean of all offspring from the same parental strain. We thus identified 17 mutant pedigrees (6%), all exhibiting hearing loss at high frequencies (> or = 16 kHz) with an average threshold elevation of 30-35 dB SPL. Interestingly, four mutants showed sex-biased hearing loss and six mutants displayed wide range frequency hearing loss. Temporal bone histology revealed that six of the first nine mutants displayed cochlear morphological defects: degeneration of spiral ganglia, spiral ligament fibrocytes or inner hair cells (but not outer hair cells) mostly in basal turns. In contrast to other ENU-mutagenesis auditory screens, our screen identified high-frequency, mild and sex-biased hearing defects. Further characterization of these 17 mouse models will advance our understanding of presbycusis and noise-induced hearing loss in humans.

[Orientation of three lysosomal enzymes in the mouse inner ear and hearing loss in enzyme gene deficiency].

OBJECTIVE: To determine the distribution and influence of lysosomal neuraminidase (Neul), protective protein/cathepsin A (PPCA) and beta-galactosidase (beta-gal) in the inner ear of the mouse, and to observe their auditory alterations in enzyme deficiency. METHODS: Six wild type (2 months postnatal) (Neu1+/+, PPCA+/+ and beta-gal+/+) mice were used, and Neu1, PPCA and beta-gal homozygous (Neu1-/-, PPCA-/- and beta-gal-/-) mice at the same age used as control in this experiment. The auditory thresholds were examined through the auditory brainstem responses (ABR) to click, which tone pips were 8, 16, and 32 kHz. The mice were intracardically perfused with 4% paraformaldehyde. The bulla were further fixed in 4% paraformaldehyde, processed and sectioned with paraffin embedded method. Immunohistochemistry was used to determine the cellular localizations of Neu1, PP-CA, and beta gal in the inner ear. RESULTS: There was a similar distributive pattern of Neu1, PPCA and betagal in the inner ear. Neu1 intense staining was observed in the cochlear spiral ganglion cells, spiral limbus, spiral ligament, vestibular ganglion cells, cristae, maculae hair cells, and weak staining in inner hair cells, outer hair cells, supplying cells of the organ of Corti and stria vascularis. The intense staining of PPCA and beta-gal were observed in the spiral ganglion and vestibular ganglion cells, and weak staining in the spiral limbus, spiral ligament, stria vascularis and organ of Corti. The inner ear exhibited no staining when Neul, PPCA and beta-gal were deficient, respectively. A positive staining of PPCA and beta-gal was presented in Neu1-/- mice, and as well as Neu1 and PPCA in beta-gal-/- mice. However, the staining of Neu1 was not presented, and only very weak staining of beta-gal in PPCA-/- mice. The auditory thresholds of Neul, PPCA, and beta-gal mice were elevated for 60-69 dB, 40-48 dB, and 7-10 dB above those of wildtype littermates, respectively. CONCLUSION: Neu1 PPCA and beta-gal are distributed in the inner ear of mouse, and the three enzymes also form a lysosomal multi-enzyme complex in the inner ear. The respective enzyme deficiencies can induce the hearing the loss of different levels.

Morphological and functional alterations of the cochlea in apolipoprotein E gene deficient mice.

The relationship between hyperlipidemia and sensorineural hearing loss remains obscure. In this study, we elucidate for the first time the cochlear morphological and auditory alterations and their relationships with hyperlipidemia, atherosclerosis, and endothelial dysfunction in apolipoprotein-E knockout (ApoE-KO) mice. Ten-week-old ApoE-KO mice were fed either atherosclerotic diet (1.25% cholesterol) or normal diet. Wild type mice (C57BL/6J) served as normal controls. Fourteen weeks later, marked hyperlipidemia, atherosclerosis, endothelial dysfunction, and hearing impairment, especially in the high frequencies, had developed in ApoE-KO mice as compared with C57BL/6J mice (P<0.001). A high positive correlation between hearing loss and the extent of atherosclerosis and plasma total cholesterol levels was found. Hearing loss, especially at high frequencies, was detected in all ApoE-KO mice. Hair cell loss mainly at the base turn, thickening of vascular intima, and lumen stenosis of the spiral modiolar artery (SMA) in cochlea were also found; these histological changes were exacerbated by the atherosclerotic diet. Furthermore, endothelial nitric oxide synthase (eNOS) in aortic wall and cochlea was distinctly reduced in ApoE-KO mice. These results demonstrate that hyperlipidemia and atherosclerosis can induce alterations in cochlear morphology and function. The stenosis of SMA, which may cause cochlear ischemia and hypoxia, endothelial dysfunction, and low eNOS activity, may contribute to hearing loss.

[Clinical observation of sensorineural hearing loss in patients suffering from nasopharyngeal carcinoma after radiotherapy].

OBJECTIVE: To study the extent and incidence of sensorineural hearing loss (SNHL) after radiotherapy (RT). METHODS: Twenty-eight patients with diagnosed nasopharyngeal carcinoma (NPC) were selected. The pure-tone audiography, auditory brain stem evoked response (ABR), impedance audiometry and evoked otoacoustic emissions (EOAE) recordings were performed before RT, 1 month, 1, 2 and 5 years after RT. RESULTS: At 1 month after RT, there were 7.1 and 25.7 dB increased mean bone conduction (BC) thresholds at speech (0.5 - 4.0 kHz) and at high frequency (8.0 kHz), and their BC thresholds were statistically significant increase than those before RT, respectively (P < 0.001). At 1 year after RT, there were 17.6 and 28.1 dB increased respectively, and their thresholds were statistically significant increase than those at pre-irradiation (P < 0.001). There were also significant increases in thresholds than those at 1 month of post-irradiation (P <0.001 or P < 0.05). At 2 years after RT, 21 and 27.4 dB were increased at respective those two frequencies, and there was a statistically difference only at speech frequencies when compared with those at 1 year after RT (P < 0.05). At 5 years after RT, 26.7 and 35.8 dB were increased at these two frequencies, and there were significant increases in threshold than those before, 1 month, 1 and 2 years after RT, respectively (P < 0.001). From 1 month to 5 years after RT, 37. 5% to 94. 7% of ears had a BC hearing threshold of at least 15 dB losses at speech frequency, whereas the percentage at high frequency was 85.4 to 97.4%. Up to 63.2% and 73.7% of ears had 30 dB SNHL at least at speech and high frequency, respectively. Furthermore, the degree of mean threshold loss was greater at high frequency than at speech frequency. The mean value of wave I, III and V latency, and I -V interpeak latency intervals of ABR had no significant difference between at 1 month after RT and before RT (P > 0.05). The wave I , III and V latency, and I - V interpeak latency intervals at 1 year and 2 years were significantly prolonged when compared with those before and 1 month after RT (P < 0.05), but there were no significant difference between 1 year and 2 years after RT (P > 0.05). The wave I, III and V latency, and I -V interpeak latency intervals at 5 years after RT were also significantly longer than those before RT (P < 0.001). There were significant difference in wave I , III and V latency (P < 0.05), and no significant difference in wave I - V interpeak latency intervals (P > 0. 05) between 5 years after RT and 1 year or 2 years after RT. Seven of 10 ears at 1 year after RT and 4 of 7 ears at 5 years after RT had normal EOAE, but they all had abnormal ABR response. CONCLUSIONS: SNHL in NPC patients start soon after completion of RT, especially more commonly in high frequency. The incidence and the extent of hearing loss are increased with time of follow-up. The hearing impairment could occur in the cochlea and/or the retrocochlear auditory pathway, which show that the sensitivity of radiation damage may be different in different patient and anatomic site of auditory system.

[Morphological and functional alterations of ear in lysosomal neuraminidase gene deficient mouse].

OBJECTIVE: To observe the alterations of the auditory function and morphology of the ear in the mouse sialidosis models which has been generated by targeted deletion of lysosomal neuraminidase gene (Neul) and closely resembled the phenotypes in corresponding human conditions, and to explore pathophysiological mechanisms of hearing impairment. METHODS: Neul homozygous (Neul -/-) mice at 3 weeks, 2 and 4 months of age, and their wildtype littermates (Neu1 +/+) were examined for auditory thresholds through auditory brainstem responses (ABR) to click, 8, 16, and 32 kHz stimuli. Morphological analyses in ears were performed by series temporal bone section and light microscopy. RESULTS: Neul -/- mice at 3 weeks of age showed an elevated ABR threshold, 50-55 dB above those of Neul +/+ mice. Up to 2 and 4 months of age, their thresholds were further elevated for 60-68 dB. There were distinct pathological changes of middle and inner ear of 3 weeks of age in Neul -/- mice, especially at 2-4 months of age there were significant cerumen occlusion in the external auditory canal and severe otitis media. Vacuolation associated with lysosomal storage was observed within ossicles and cochlear bone cells, stria vascularis cells, spiral ganglion neurons and macrophages, spiral limbus, spiral prominence, Reissner's membrane cells, and the mesothelial cells of the perilymphatic scala and basilar membrane, but not within the organ of Corti. Vestibular ganglion neurons, hair cells and supporting cells in cristae and maculae also showed vacuolation. CONCLUSIONS: The deficiency of lysosomal neuraminidase may result in a serious hearing loss and morphological alterations of ear. The external auditory canal obstruction, otitis media and ossicle changes may cause conductive hearing loss, and the defects in lysosomal storage of neurons, stria vascularis, spiral limbus, Reissner's membrane and basilar membrane cells may contribute to sensorineural deafness.

Hearing threshold elevation precedes hair-cell loss in prestin knockout mice.

Our previous characterization of prestin knockout (-/-) mice demonstrated that prestin is required for the eletromotility of outer hair cells (OHCs) and for the cochlear amplifier. Because hair-cell loss was observed in the basal 25% of cochleae in adult prestin-/- mice, it remained unclear how hair-cell loss progressed, whether hearing thresholds were elevated, and whether OHCs had normal ultra-structure in young prestin-/- mice. We report here that in prestin-/- mice, no significant hair-cell loss occurred before postnatal day 28 (P28); apoptosis of hair cells began at P28; and the loss of inner hair cells lagged behind that of OHCs. The prestin-/- mice had hearing thresholds that were significantly elevated (by approximately 25 dB) as early as P14; their thresholds at high frequencies were significantly elevated (by approximately 50 dB) at P21. The prestin heterozygous (+/-) mice displayed a significant threshold elevation (approximately 3.5 dB) at P21. In addition, transmission electronic microscopy shown that no obvious abnormality occurs in the sterocilla, lateral wall, tight junction and synapses of the outer hair cells. Our results demonstrate that the absence of prestin, not hair-cell loss, is the primary cause of high-frequency hearing threshold elevation in prestin-/- and +/- mice.

[Noninvasive and invasive naso-sinus fungus: 35 cases report].

OBJECTIVE: To study the clinical features, diagnosis and management of nose and nasal sinuses fungus. METHOD: Different manner of surgical procedure was taken according to the areas and degree of pathological changes. The patients with noninvasive fungus were treated with radical maxillary sinusotomy (cald-well-Luc operation) or endoscopic sinus surgery. The patients with invasive form were undergone by the sinusotomy of enlarging areas, and combined with a postoperatively antifungal therapy. RESULT: Twenty-six patients were involved in noninvasive fungus, and 25 cases in them were cured in single surgery through different manner. Nine patients were in invasive one, and 7 in them were also cured by single surgery in different manner. One patient with invasive fungus died 5 months postoperatively for extensive area and non effective treatment although four surgical excisions were done. CONCLUSION: CT scan is very important in their diagnosis, and the histopathology leads to identification of the fungus. Surgical removal is a radical kind of treatment. It is essential to excise and open entirely the involved sinus cavity whatever type,and to enlarge areas for the extensive invasive fungus.