Objectives:To investigate the protective effect of nicotinamide adenine dinucleotide (NAD?) against noise-induced cochlear damage and preliminarily explore its underlying transcriptional and metabolic regulatory mechanisms.Methods:During the study period (January 2023-February 2025), an oxidative stress model was established using House Ear Institute-organ of Corti 1 (HEI-OC1) cells, and cell viability was assessed using the Cell Counting Kit-8 (CCK8) assay. Flow cytometry was employed to analyze cell apoptosis. A mouse model of noise-induced hearing loss was developed, and the mice were divided into three groups: a noise-exposed saline group, a noise-exposed NAD? intervention group, and a noise-free control group. Hearing protection effects were evaluated by auditory brainstem response (ABR) and immunofluorescence. Metabolomics and transcriptomics were used to analyze the regulatory effects of NAD +on transcription and metabolism in mouse cochlea. Enzyme-linked immunosorbent assay, quantitative real-time PCR, and western blot were used to verify the differential transcription and metabolic molecules and their functions. Data were statistically analyzed with GraphPad Prism 9.3.0. Results:NAD +at concentrations ranging from 10-80 μM effectively restored cell viability and reduced apoptosis induced by H?O? in HEI-OC1 cells. NAD? intervention significantly improved 16-32 kHz ABR thresholds after noise exposure ( P<0.05), reduced outer hair cell loss rates ( P<0.05), and attenuated ribbon synapse damage ( P<0.000 1). Metabolomics analysis revealed a significant downregulation in the glycerophospholipid metabolism pathway, with decreased levels of lysophosphatidic acid (LPA) and its related metabolites. ELISA results showed that LPA levels in the NAD? intervention group were significantly lower ( P<0.05). LPA inhibitor (ATX inhibitor 1) exhibited a cell protective effect similar to that of NAD?. Transcriptomics analysis indicated a significant upregulation of key genes related to potassium ion channels, such as Kcnq4. qPCR and Western blot further confirmed the significant upregulation of Kcnq4 and its encoded protein in the NAD? intervention group ( P<0.05). In the presence of the KCNQ4 inhibitor (ML252), the protective effect of NAD? was inhibited. Conclusions:NAD? exerts effective protective effects against noise-induced cochlear injury. Its protective mechanism may be closely related to the inhibition of LPA metabolic pathway and the up-regulation of KCNQ4 channel function.

Objectives:To investigate the protective effect of nicotinamide adenine dinucleotide (NAD?) against noise-induced cochlear damage and preliminarily explore its underlying transcriptional and metabolic regulatory mechanisms.Methods:During the study period (January 2023-February 2025), an oxidative stress model was established using House Ear Institute-organ of Corti 1 (HEI-OC1) cells, and cell viability was assessed using the Cell Counting Kit-8 (CCK8) assay. Flow cytometry was employed to analyze cell apoptosis. A mouse model of noise-induced hearing loss was developed, and the mice were divided into three groups: a noise-exposed saline group, a noise-exposed NAD? intervention group, and a noise-free control group. Hearing protection effects were evaluated by auditory brainstem response (ABR) and immunofluorescence. Metabolomics and transcriptomics were used to analyze the regulatory effects of NAD +on transcription and metabolism in mouse cochlea. Enzyme-linked immunosorbent assay, quantitative real-time PCR, and western blot were used to verify the differential transcription and metabolic molecules and their functions. Data were statistically analyzed with GraphPad Prism 9.3.0. Results:NAD +at concentrations ranging from 10-80 μM effectively restored cell viability and reduced apoptosis induced by H?O? in HEI-OC1 cells. NAD? intervention significantly improved 16-32 kHz ABR thresholds after noise exposure ( P<0.05), reduced outer hair cell loss rates ( P<0.05), and attenuated ribbon synapse damage ( P<0.000 1). Metabolomics analysis revealed a significant downregulation in the glycerophospholipid metabolism pathway, with decreased levels of lysophosphatidic acid (LPA) and its related metabolites. ELISA results showed that LPA levels in the NAD? intervention group were significantly lower ( P<0.05). LPA inhibitor (ATX inhibitor 1) exhibited a cell protective effect similar to that of NAD?. Transcriptomics analysis indicated a significant upregulation of key genes related to potassium ion channels, such as Kcnq4. qPCR and Western blot further confirmed the significant upregulation of Kcnq4 and its encoded protein in the NAD? intervention group ( P<0.05). In the presence of the KCNQ4 inhibitor (ML252), the protective effect of NAD? was inhibited. Conclusions:NAD? exerts effective protective effects against noise-induced cochlear injury. Its protective mechanism may be closely related to the inhibition of LPA metabolic pathway and the up-regulation of KCNQ4 channel function.

Objective:This study evaluates the agreement between a new low-load sleep monitoring system, QSA600, based on millimeter-wave radar technology, and polysomnography (PSG) in diagnosing obstructive sleep apnea (OSA).Methods:A total of 155 subjects were recruited for a parallel agreement study in the sleep laboratory of the Department of Otorhinolaryngology Head and Neck Surgery at Shanghai Sixth People′s Hospital from July to September 2023. The subjects underwent simultaneous monitoring with both PSG and the QSA600 system. One hundred and forty-five subjects consisting of 75 males and 70 females included in the final analysis, with an average age of (35.30±12.41) years, an average height of (168.23±8.08) cm, and an average weight of (68.28±13.74) kg. The subjects were divided into four groups based on the apnea-hypopnea index (AHI): <5.0 events/h (non-OSA group, 39 cases), ≥5.0-<15.0 events/h (mild OSA group, 47 cases), ≥15.0-<30.0 events/h (moderate OSA group, 25 cases), and≥30.0 events/h (severe OSA group, 34 cases). Intraclass correlation coefficients (ICC), Pearson correlation coefficients ( r), and Bland-Altman analysis were employed to assess the agreement between the two monitoring techniques regarding AHI and other parameters. Sensitivity and specificity of the QSA600 in diagnosing OSA were evaluated at different AHI thresholds. Statistical analyses were conducted using MATLAB R2022a. Results:Using AHI 5 events/h, 15 events/h and 30 events/h as thresholds, the sensitivity for diagnosing mild, moderate, and severe OSA was 88.68%, 89.83% and 97.06%, respectively. The specificity was 94.87%, 98.84% and 99.10%, respectively. The areas under the receiver operating characteristic (ROC) curve was 0.973 4, 0.990 9 and 0.999 5, respectively. The comparison of key indicators between QSA600 and PSG diagnostic results revealed:a Pearson correlation coefficient of 0.987 2( P<0.001) between the AHI measurement values. The mean difference between the Bland-Altman measurement values of the two was -1.43(95% CI:-8.74-5.88) events/h and the ICC between the two was 0.985 0(95% CI: 0.975 4-0.990 4). Conclusions:As a new low-load sleep monitoring system, QSA600 demonstrates high concordance with traditional PSG in diagnosing OSA and stratifying its severity, which has promising potential for clinical application. (Clinical trial registration number: NCT06038006)

Objective·To explore the correlation between the genetic variations rs7305526 and rs11615756 of nitric oxide synthase 1(NOS1)and the human sleep traits,including insomnia,sleep duration,and clinical quantitative traits related to obstructive sleep apnea(OSA).Methods·The NOS1 gene expression pattern at the whole-brain level using the Allen Human Brain Atlas dataset was analyzed.Subsequently,we performed expression quantitative trait locus(eQTL)analysis to investigate the impact of rs7305526 and rs11615756 on NOS1 gene expression.Regression analysis was conducted to assess the associations between rs7305526 and rs11615756 with insomnia and sleep duration based on the United Kingdom Biobank(UKB)Genome-Wide Association Study(GWAS)dataset.Furthermore,we explored the relationships between rs7305526 and rs11615756 with clinical quantitative traits of OSA,such as respiratory events,oxygen levels,and sleep traits,using clinical monitoring data from the Shanghai Sleep Health Study Cohort(SSHS)based on standard polysomnography(PSG).Results·The NOS1 gene demonstrated elevated levels of expression in various brain regions crucial for regulating sleep,namely the amygdala,basal forebrain,striatum,and thalamus,as well as in the respiratory center,including the mesencephalon and pontine tegmentum.In contrast,the expression level of NOS1 gene was significantly reduced or absent in areas such as the cerebral cortex and cerebellum.Variants rs7305526 and rs11615756 were significantly negatively correlated with the expression levels of NOS1 in the cerebral cortex.Additionally,rs11615756 was also significantly negatively correlated with the expression level of NOS1 in the amygdala.Analysis of the UKB GWAS data revealed that the variant rs7305526 was not significantly associated with either insomnia or sleep duration,while rs11615756 demonstrated a noteworthy negative correlation specifically with sleep duration.Data obtained from the SSHS indicated a significant association between rs7305526 and alterations in clinical quantitative traits of OSA,including lowest pulse blood oxygen saturation(LSpO2),apnea-hypopnea index(AHI),and the ratio of non-rapid eye movement(NREM)stage 2 sleep duration.Although rs11615756 showed a notable negative correlation solely with the quantity of NREM stages 2 and 3,both rs11615756 and rs7305526 showed significant correlations with some respiratory events and oxygen traits after stratification according to the severity of OSA.Conclusion·Genetic variants of NOS1 gene are respectively associated with human sleep duration traits and OSA-related variables,suggesting that NOS1 gene plays a crucial regulatory role in human sleep and clinical quantitative traits of OSA.The regulation of sleep traits by rs7305526(C>A)is independent of its regulation of respiratory events and oxygen traits.

Objective·To explore the correlation between the genetic variations rs7305526 and rs11615756 of nitric oxide synthase 1(NOS1)and the human sleep traits,including insomnia,sleep duration,and clinical quantitative traits related to obstructive sleep apnea(OSA).Methods·The NOS1 gene expression pattern at the whole-brain level using the Allen Human Brain Atlas dataset was analyzed.Subsequently,we performed expression quantitative trait locus(eQTL)analysis to investigate the impact of rs7305526 and rs11615756 on NOS1 gene expression.Regression analysis was conducted to assess the associations between rs7305526 and rs11615756 with insomnia and sleep duration based on the United Kingdom Biobank(UKB)Genome-Wide Association Study(GWAS)dataset.Furthermore,we explored the relationships between rs7305526 and rs11615756 with clinical quantitative traits of OSA,such as respiratory events,oxygen levels,and sleep traits,using clinical monitoring data from the Shanghai Sleep Health Study Cohort(SSHS)based on standard polysomnography(PSG).Results·The NOS1 gene demonstrated elevated levels of expression in various brain regions crucial for regulating sleep,namely the amygdala,basal forebrain,striatum,and thalamus,as well as in the respiratory center,including the mesencephalon and pontine tegmentum.In contrast,the expression level of NOS1 gene was significantly reduced or absent in areas such as the cerebral cortex and cerebellum.Variants rs7305526 and rs11615756 were significantly negatively correlated with the expression levels of NOS1 in the cerebral cortex.Additionally,rs11615756 was also significantly negatively correlated with the expression level of NOS1 in the amygdala.Analysis of the UKB GWAS data revealed that the variant rs7305526 was not significantly associated with either insomnia or sleep duration,while rs11615756 demonstrated a noteworthy negative correlation specifically with sleep duration.Data obtained from the SSHS indicated a significant association between rs7305526 and alterations in clinical quantitative traits of OSA,including lowest pulse blood oxygen saturation(LSpO2),apnea-hypopnea index(AHI),and the ratio of non-rapid eye movement(NREM)stage 2 sleep duration.Although rs11615756 showed a notable negative correlation solely with the quantity of NREM stages 2 and 3,both rs11615756 and rs7305526 showed significant correlations with some respiratory events and oxygen traits after stratification according to the severity of OSA.Conclusion·Genetic variants of NOS1 gene are respectively associated with human sleep duration traits and OSA-related variables,suggesting that NOS1 gene plays a crucial regulatory role in human sleep and clinical quantitative traits of OSA.The regulation of sleep traits by rs7305526(C>A)is independent of its regulation of respiratory events and oxygen traits.

Objective:To evaluate the associations between the renalase single-nucleotide polymorphisms rs2576178 and rs10887800 and the risk of hypertension in OSA patients. Methods:A total of 3, 570 male OSA subjects diagnosed via standard polysomnography were included in this retrospective study. We recorded anthropometric, genomic, and polysomnographic parameters and blood pressure levels. All subjects were divided into four groups based on quartiles of the apnea-hypopnea index (AHI). The relationships between rs2576178 and rs10887800 and the risk of hypertension were evaluated using the binary logistic regression, and haplotype analysis.Results:In the bottom AHI quartile, rs10887800 was significantly associated with the risk of hypertension according to the dominant model [odds ratio( OR)=0.691, 95% confidence interval ( CI)=0.483-0.990, P=0.044] even after adjustment for age, sex, and the body mass index. The G-A haplotype was associated with a co-effect of the two SNPs, namely, the risk of hypertension decreased ( OR=0.879, 95% CI=0.784-0.986, P=0.028). Conclusions:We find no association between single rs2576178 or rs10887800 variants with the risk of hypertension in our OSA population. But, the synergistic effect of the two polymorphisms is associated with the risk of hypertension in OSA patients.

Objective:To investigate the expression of long non-coding RNA (Lnc RNA) RP5-919F19 in gastric cancer tissues and its correlation with gastric cancer invasion and metastasis.Methods:Non-tumor gastric mucosa (more than 3cm away from the cancer tissue) and gastric adenocarcinoma tissues were collected from Jan. 2020 to Jan. 2022 in our hospital. TRIzol kit was used to extract total RNA from cells and tissues, and reverse transcription kit was used to reverse transcribed RNA into cDNA. Quantitative real-time PCR kit was used for quantitative analysis. SGC-7901 and AGS human gastric cancer cells were used to construct RP5-919F19 knockdown and overexpression models. CCK-8 assay was used to confirm cell proliferation, and Transwell invasion assay was used to confirm the invasion ability of gastric cancer cells.Results:The expression of RP5-919F19 was detected in 79 cases of gastric cancer tissues and adjacent normal tissues, and it was found that the relative expression of RP5-919F19 in gastric cancer tissues was 1.51±0.05 significantly higher than that of 0.82±0.04 in adjacent normal tissues ( P<0.05) . The levels of RP5-919F19 in patients with different pathological conditions were compared and analyzed. The results showed that there were statistically significant differences in RP5-919F19 expression in patients with different TNM stages, distant metastasis, lymph node metastasis and different depth of invasion ( P<0.05) . There was no significant difference in RP5-919F19 expression among patients with different tumor sizes, ages and genders ( P>0.05) . AGS gastric cancer cells were transfected with RP5-919F19 overexpression plasmid and control plasmid, and the efficiency of RP5-919F19 was detected. The results showed that the expression level of RP5-919F19 in the overexpression group was 1.83±0.14 higher than that of 0.82±0.05 in the control group ( P<0.05) . SGC-7901 gastric cancer cells were transfected with RP5-919F19 knockout vector and control vector, and the efficiency of RP5-919F19 was detected. The results showed that the expression level of RP5-919F19 in the knockout group was 0.42±0.07 lower than that of 0.89±0.08 in the control group ( P<0.05) . CCK-8 was used to detect the proliferation ability of gastric cancer cells. The results showed that the proliferation ability of AGS cells in RP5-919F19 overexpression group was significantly increased compared with that of the control group at 24 and 48h after culture ( P<0.05) . However, the proliferation ability of SGC-7901 cells in RP5-919F19 knockdown group was lower than that in the control group at 24 h and 48 h ( P<0.05) . Transwell invasion assay showed that the invasion and migration abilities of AGS cells in RP5-919F19 overexpression group were higher than those in the control group ( P<0.05) , and the invasion and migration abilities of SGC-7901 cells in RP5-919F19 knockout group were lower than those in the control group ( P<0.05) . Western blot showed that compared with control cells, the expression of MMP-2 and MMP-9COPS7A proteins in down-regulated Lnc RNA RP5-919F19 SGC-7901 cells was decreased. Conclusion:The expression of LncRNA RP5-919F19 is abnormally increased in gastric cancer tissues, and the increased expression of RP5-919F19 can promote the proliferation and metastasis of gastric cancer cells.

Objective: To compare the therapeutic efficacy of Han-uvulopalatopharyngoplasty (HUPPP) combined with radiofrequency ablation of tongue base or HUPPP with traction of tongue base on moderate to severe patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: This is a multicenter randomized controlled trial. From March 2017 to July 2019, moderate to severe OSAHS patients from three clinical center in Shanghai who were intolerant to continuous positive airway pressure (CPAP) and with velopharyngeal and glossopharyngeal plane obstruction were enrolled in this study. According to the surgical type, they were 1∶1 randomized to HUPPP plus radiofrequency ablation of tongue base group (Ablation group) or HUPPP plus traction of tongue base group (Traction group). All patients completed over-night standard Polysomnography (PSG), upper-airway assessment (Friedman classification, Müller test, CT and cephalometric examination), preoperative routine examination, Epworth Sleepiness Scale (ESS) and Quebec sleep questionnaire (QSQ). Six to 12 months after operation, all the above-mentioned examinations were repeatedly performed. Changes of aforementioned variables before and after operation were assessed. Results: A total of 43 patients with moderate to severe OSAHS were enrolled in this study. One patient lost to follow-up, the remaining 21 were allocated to Ablation group and 21 were allocated to Traction group. The total therapeutic efficacy of all patients was 69.05% (61.90% in Ablation group and 76.19% in Traction group), but there was no statistical significance between the two groups (P= 0.317). The value of sleep scale score (ESS and QSQ), objective sleep variables (apnea-hypopnea index, oxygen saturation, percentage of time with blood oxygen less than 90% in total sleep time, oxygen desaturation index and micro-arousals) and upper airway cross-sectional area (palatopharyngeal and retrolingual area) of the two groups were improved (P<0.05), but the differences between the two groups were not statistically significant (P>0.05). Conclusion: For moderate to severe OSAHS who had glossopharyngeal plane obstruction, both HUPPP plus radiofrequency ablation of tongue base or HUPPP plus traction of tongue base are effective treatment for OSAHS, and the curative effect is similar. The choice of surgical type could be selected according to patient's or surgical conditions.
China ; Humans ; Oxygen Saturation ; Radiofrequency Ablation ; Sleep Apnea, Obstructive/surgery* ; Tongue/surgery* ; Traction

OBJECTIVE: The role of different local flaps in small external nasal skin defect reconstruction was discussed. METHOD: Forty-two cases of the small size nasal defects (diameter < 2 cm) were repaired with local external nose flap (includes the dorsal nasal flap, nasolabial flap and bilobed flap). The clinical and follow-up data were analyzed of patients with small external nasal skin defects, who accepted different local flaps reconstruction. Dorsal nasal flap, nasolabial flaps (includes island flap, slid flap and axial flap) and bilobed flap were tailored to reconstruct different external nasal defect. Twenty-seven patients were male and fifteen patients were female, the patients' age ranged from 28 to 74 years, the median age was 61 years. Thirty-eight cases resulted from resection of skin malignant tumor and four cases were benign lesions. The diameter of defects was 1-2 cm. The defects were reconstructed by single-stage dorsal nasal flap in 7 cases. There were 30 cases of caudolateral nasal defects were reconstructed by nasolabial flap, single-stage island nasolabial flap in 7 cases, axial flap in 18 cases and slid flap in 5 cases. Superior lateral defects were reconstructed by single-stage bilobed flap in 5 cases. RESULT: All defects were repaired successfully. All tissue flaps survived and had not necrosis. There was no tumor recurrence during 3 months to 2 years follow-up. CONCLUSION The dorsal nasal flap, nasolabial flap and bilobed flap can be used safely and effectively to repair the small external nasal defect and have satisfactory curative effect.
Adult ; Aged ; Dermatologic Surgical Procedures ; methods ; Face ; pathology ; surgery ; Female ; Humans ; Male ; Middle Aged ; Nose ; pathology ; surgery ; Reconstructive Surgical Procedures ; methods ; Skin ; pathology ; Surgical Flaps

Objective:To evaluate the difference of vestibular compensation between triple semicircular canal occlusion(TCO) and labyrinthectomy(LE)in guinea pigs.Material and Methods:TCO was performed on 8 guinea pigs,while LE was did on 7 guinea pigs.Behavior and ENG were recorded in detail preoperatively and repeatedly up to one month postoperatively according to the experiment design.Results:There was spontaneous nystagmus towards the nonoperated side on the first postoperative day and nystagmus absence during sinusoidal angular acceleration stimuli on the operated side was observed in all the animals.All the animals displayed head tilt towards the operated side (right)and an unsteady gait towards the right along the vertical axis after surgery,while the animals performed LE rolled towards the operated side.On the 3rd postoperative day,faint nystagmus appeared on the operated side,but the left and right nystagmus was significantly asymmetrical.The left and right nystagmus still remained asymmetrical on the 5th and 10th day postoperatively.From the 15th postoperative day,left and right nystagmus returned symmetrical in the animals performed TCO,while left and right nystagmus returned symmetrical only at the pendular amplitude of 120°,150°,180°,in the animals performed LE up to 30th postoperative day.There was a significant reduction of nystagmus to the operated side at the Pendular amplitude of 60°and 90° one month after the LE and there was 3 animals still displayed head tilt towards the operated side.Conclusion: the animals compensated faster and more completely after TCO than LE.