Objective:To explore the symptoms of Ménière′s disease patients and their impact on quality of life.Methods:A cross-sectional study was conducted, consecutively enrolling patients of Ménière′s disease who visited the Otolaryngology Clinic at the Eye & ENT Hospital of Fudan University from October 2014 to December 2022. The Chinese version of the Ménière′s Disease Outcomes Questionnaire (MDOQ) and a Ménière′s disease-specific symptom checklist were utilized for assessment. SPSS 25.0 software was employed to perform multiple linear regression analysis to determine the impact of Ménière′s disease symptoms on patients′ quality of life.Results:A total of 790 patients with a definitive diagnosis of Ménière′s disease who met the inclusion and exclusion criteria were analyzed. The cohort comprised 418 males and 372 females, with a mean age of (54.8±13.1) years and a diagnosis duration ranging from 0 to 72 months, with a median of 3 months. The total score of the Chinese MDOQ was 61.0±12.0. The symptomatic presentations of the enrolled patients included hearing changes, tinnitus, aural fullness, drop attacks, vertigo episodes, visual instability, dizziness, and headache. Multiple linear regression analysis revealed that age, tinnitus, aural fullness, frequency of drop attacks, visual instability, dizziness, and headache were significant factors affecting the quality of life in Ménière′s disease patients ( F=145.50, P<0.05). Conclusions:The quality of life in Ménière′s disease patients requires improvement. Attention to the specific symptoms of Ménière′s disease and their impact on patients′ quality of life, along with targeted symptom interventions based on these findings, will be a focal point in future disease management.

Objective:To establish and evaluate a second-tier screening method for neonatal congenital adrenal hyperplasia (CAH) and develop appropriate screening interpretation criteria.Methods:We employed liquid chromatography-tandem mass spectrometry to simultaneously detect five steroid hormones in dried blood spots: 17α-hydroxyprogesterone (17α-OHP), androstenedione (A4), 11-deoxycortisol (11-DOC), 21-deoxycortisol (21-DOC), and cortisol (F), calculating (17α-OHP+A4)/F and (17α-OHP+21-DOC)/F ratios for second-tier CAH screening. The study utilized 429 residual dried blood spot samples from neonates (0-7 days) who completed first-tier screening between January 2020 and March 2024 in Guangzhou Women and Children's Medical Center, Guangzhou Medical University, including first-tier negatives ( n=369), confirmed false positives ( n=50), and CYP21A2-confirmed 21-hydroxylase deficiency patients ( n=10). Mann-Whitney U and Kruskal-Wallis tests analyzed steroid concentration variations across gestational ages and birth weights in all negative samples, with reference intervals established via P2.5- P97.5 percentiles and screening cutoffs set at population P97.5. Receiver operating characteristic (ROC) curve analysis identified optimal interpretation indicators among steroid hormone profiles, with second-tier screening performance evaluated by comparing sensitivity and specificity across different steroid hormone indicators to establish the optimal diagnostic criteria. Results:The five steroid hormones demonstrated intra-assay precision with coefficient of variation (CV) of 9.8%-14.2% and inter-assay precision with CV of 4.7%-14.4% across three different concentration levels of quality control materials. Accuracy ranged from 98.5% to 110.0% and the lower limits of quantification were 0.25 ng/ml for 17α-OHP, 0.05 ng/ml for A4/11-DOC, 0.31 ng/ml for 21-DOC, and 0.1 ng/ml for F. Stratification by gestational age categorized 17α-OHP into ≤31, 32-34, and ≥35 weeks; A4 into ≤31, 32-36, and ≥37 weeks; and 11-DOC into ≤31 and ≥32 weeks, while the remaining indicators were not stratified. When grouped by birth weight (low/normal), all measured parameters except 21-DOC showed statistically significant differences between groups (all P<0.05). Established reference intervals included 17α-OHP: 0.53-7.82 ng/ml (≤31 weeks), <0.25-3.60 ng/ml (32-34 weeks), <0.25-1.64 ng/ml (≥35 weeks); A4: 0.12-2.36 ng/ml (≤31 weeks), <0.05-1.45 ng/ml (32-36 weeks), 0.17-0.95 ng/ml (≥37 weeks); 11-DOC: 0.43-4.04 ng/ml (≤31 weeks), 0.08-1.46 ng/ml (≥32 weeks); F: 1.70-83.70 ng/ml; 21-DOC: <0.31-0.69 ng/ml; (17α-OHP+A4)/F: 0.01-0.74; and (17α-OHP+21-DOC)/F: 0.01-0.69. Comprehensive comparison of CAH second-tier screening performance demonstrated that interpretation based on elevated 17α-OHP accompanied by either elevated 21-DOC or elevated ratios [(17α-OHP+A4)/F or (17α-OHP+21-DOC)/F] achieved 100% sensitivity, 96% specificity, and a 96% reduction in false-positive rate. Conclusion:The application of liquid chromatography-tandem mass spectrometry for multi-steroid hormone profiling in second-tier neonatal CAH screening, utilizing gestational age-specific 17α-OHP cutoffs combined with elevated 21-DOC or ratio criteria, demonstrated 100% screening sensitivity while substantially reducing false-positive rates from primary screening, though further validation with expanded sample sizes remains necessary.

Psoriasis is a chronic inflammatory skin disease, and its pathogenesis is largely modulated by abnormal angiogenesis. Previous research has indicated that AlkB homolog 5 (ALKBH5), an important demethylase affecting N⁶-methyladenosine (m⁶A) modification, plays a role in regulating angiogenesis in cardiovascular and eye diseases. Our present study found that ALKBH5 was upregulated and co-localized with cluster of differentiation 31 (CD31) in the skin of IMQ group compared with control group. ALKBH5-deficient mice decreased IMQ-induced psoriatic dermatitis and exhibited histological improvements, including decreased epidermal thickness, hyperkeratosis, numbers of dermal capillary vessels and inflammatory cell infiltration. ALKBH5-KO mice alleviated angiogenesis in psoriatic lesions by downregulating the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. Additionally, the expression of ALKBH5 was significantly upregulated in IL-17A-induced human umbilical vein endothelial cells (HUVECs), which further promoted the expression of angiogenesis-related cytokines and endothelial cell proliferation. Cell proliferation and angiogenesis were suppressed in ALKBH5 knockdown group, whereas ALKBH5 overexpression promoted these processes. The regulation of angiogenesis in HUVECs by ALKBH5 was facilitated through the AKT-mTOR pathway. Collectively, ALKBH5 plays a pivotal role in psoriatic dermatitis and angiogenesis, which may offer a new potential targets for treating psoriasis.
Animals ; Psoriasis/chemically induced* ; Mice ; Humans ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; AlkB Homolog 5, RNA Demethylase/genetics* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Cell Proliferation ; Mice, Knockout ; Disease Models, Animal ; Signal Transduction ; Male ; Skin/blood supply* ; Mice, Inbred C57BL ; Angiogenesis

Objective To stratify the estrogen receptor(ER)positive while human epidermal growth factor receptor 2(HER2)negative breast cancer patients by the expression level of ER,providing new evidence for prognostic prediction and guiding precision endocrine therapy(ET)for those with different ER expression levels.Methods A retrospective cohort study was conducted on 1 962 ER-positive/HER2-negative breast cancer patients treated in our department from January 1,2013 to December 31,2018.X-tile was used to calculate the optimal cutoff point of ER expression level,and then based on the results,they were divided into low(1%～10%),moderate(11%～30%),and high expression(31%～100%)groups.After propensity score matching(PSM)was performed to balance baseline characteristics,their prognostic outcomes were compared and the responses to ET were analyzed in the groups.Cox proportional risk regression model was applied to analyze the prognostic factors,and subgroup analysis was further performed.Results After PAM,129(11.5%)were assigned into a low ER expression group,151(13.5%)and 840(75%)into moderate and high ER expression groups,respectively.Statistical differences were observed in disease-free survival(DFS)and overall survival(OS)among the 3 groups(P=8e-6,P=8e-14).In the low ER expression group,the patients treated with selective estrogen receptor modulators(SERMs)showed no significant differences in DFS and OS than those treated with aromatase inhibitors(AIs)(P>0.05).However,the patients from the moderate and high ER expression groups demonstrated significantly better DFS when treated with AI than with SERM(P=0.02,P=0.03).Multivariate analysis showed that compared with the moderate ER expression group,the high ER expression group exhibited significantly lower risk of disease recurrence/metastasis(HR=0.62,95%CI:0.43～0.88,P=0.009)and risk of death(HR=0.49,95%CI:0.26～0.93,P=0.03).Subgroup analysis revealed that when compared with the high ER expression group,the moderate ER expression group exhibited notably worse DFS in the following subgroups:oral SERM,non-breast-conserving surgery,lymph node metastasis,TNM stage Ⅱ,and chemotherapy,and shorter OS in the subgroups of oral SERM,non-breast-conserving surgery,lymph node metastasis,TNM stage Ⅱ subgroup,and chemotherapy.Conclusion Taking ER expression of 11%～30%as an independent stratification criterion can guide more accurate prognostic assessment and more rational ET selection in ER-positive/HER2-negative breast cancer patients.

Objective:To evaluate surgical strategies and clinical outcomes in supra-labyrinthine cholesteatoma management, providing evidence-based guidance for therapeutic decision-making. Methods:Seven patients with supra-labyrinthine cholesteatoma in our hospital from 2021 to 2023 were enrolled in this study. The clinical manifestations, imaging findings, and surgical outcomes of patients were retrospectively analyzed. A systematic literature review focused on surgical anatomy correlations and imaging-based approach selection. Results:All seven cases of supra-labyrinthine cholesteatoma were unilateral. Preoperative otoendoscopy, CT, and intraoperative findings confirmed that they were classified as supral-abyrinthine cholesteatoma according to Sanna's classification. Two cases were operated entirely with otoendoscopy, three cases used a postauricular approach with microscopic assistance, and two cases involved a combined approach with endoscopy and microscopy. Hearing reconstruction with ossicular prosthesis was performed in five cases, while two cases did not undergo hearing reconstruction due to preoperative anacusis confirmed by both subjective and objective hearing tests. In all seven cases, various segments of the facial nerve were exposed during surgery, but postoperative facial nerve function remained intact, hearing was preserved, no cerebrospinal fluid leakage occurred, and no recurrences have been observed to date（as of June 2024）. Conclusion:With the advancement of imaging techniques and microsurgical technology, early diagnosis and surgical methods for supral-abyrinthine cholesteatoma have significantly improved. Compared to traditional approaches, the newer methods reduce unnecessary complications and offer advantages such as minimal surgical trauma, superior hearing preservation rates, and shorter recovery times with better postoperative neural function. This study reviews recent literature on petroclival cholesteatomas, combined with our own cases, to analyze the classification of supral-abyrinthine cholesteatoma and surgical approach selection. The findings aim to optimize treatment strategies and guide appropriate surgical methods, ultimately improving patient prognosis and quality of life.
Humans ; Cholesteatoma/surgery* ; Ear, Inner/surgery* ; Retrospective Studies ; Treatment Outcome

Objective:To explore the mechanism of DEC2 deficiency promoting high incidence of post infectious cough(PIC)and the therapeutic effects of ephedrine hydrochloride(EH).Methods:C57BL/6 wild-type(WT)mice and DEC2-knockout(DEC2-KO)mice were treated with lipopolysaccharide(LPS)nose drops and smoke stimulation to establish PIC models,and some model mice were treated with EH intervention.Counting capsaicin-induced cough at 12,14,16 and 17 day of modeling;Single-cell sequenc-ing,flow cytometry,RT-qPCR and other techniques were used to detect the expressions of IL-1,IL-6,IFN-γ and other inflammatory factors and receptors in the lungs of mice before and after PIC modeling and EH intervention.The expressions of inflammatory factors and their receptors,as well as NF-κB signaling molecules,were analyzed by RT-qPCR using mouse lung CD45-primary cell culture system under LPS stimulation or EH intervention.Results:The transcription of DEC2 was increased in WT-PIC model mice,and the deficiency of DEC2 in DEC2-KO-PIC mice induced the cough frequency 2-fold higher than that in WT-PIC mice.The absence of DEC2 exacerbated LPS-induced pulmonary inflammatory response,especially increased expressions of IL-1,IL-6,IL-1Ra,IL-6Ra,IFN-γR in lung CD45-cells(P<0.01),and excessive activation of NF-κB signal(P<0.01).After EH treatment,the cough frequency in DEC2-KO-PIC mice was significantly reduced(P<0.001),the expression of IL-1,IL-6,IFN-γ in lung and IL-1Ra,IL-6Ra,IFN-γR in pulmonary CD45-cells were down-regulated(P<0.01).The expression and activation of NF-κB induced by DEC2 deletion were sig-nificantly inhibited(P<0.01).Conclusion:The deficiency of DEC2 can activate NF-κB signal and promote the high expression of in-flammatory cytokine and receptors in pulmonary CD45-cells,which is a risk factor in the high incidence of PIC.EH can inhibit the ex-cessive-activation of NF-κB signal and the inflammatory characteristics of lung local stromal cells caused by DEC2 absence,and that is the main part of pharmacological mechanism for effective treatment of EH targeting PIC.

Objective:To explore the symptoms of Ménière′s disease patients and their impact on quality of life.Methods:A cross-sectional study was conducted, consecutively enrolling patients of Ménière′s disease who visited the Otolaryngology Clinic at the Eye & ENT Hospital of Fudan University from October 2014 to December 2022. The Chinese version of the Ménière′s Disease Outcomes Questionnaire (MDOQ) and a Ménière′s disease-specific symptom checklist were utilized for assessment. SPSS 25.0 software was employed to perform multiple linear regression analysis to determine the impact of Ménière′s disease symptoms on patients′ quality of life.Results:A total of 790 patients with a definitive diagnosis of Ménière′s disease who met the inclusion and exclusion criteria were analyzed. The cohort comprised 418 males and 372 females, with a mean age of (54.8±13.1) years and a diagnosis duration ranging from 0 to 72 months, with a median of 3 months. The total score of the Chinese MDOQ was 61.0±12.0. The symptomatic presentations of the enrolled patients included hearing changes, tinnitus, aural fullness, drop attacks, vertigo episodes, visual instability, dizziness, and headache. Multiple linear regression analysis revealed that age, tinnitus, aural fullness, frequency of drop attacks, visual instability, dizziness, and headache were significant factors affecting the quality of life in Ménière′s disease patients ( F=145.50, P<0.05). Conclusions:The quality of life in Ménière′s disease patients requires improvement. Attention to the specific symptoms of Ménière′s disease and their impact on patients′ quality of life, along with targeted symptom interventions based on these findings, will be a focal point in future disease management.

Objective:To explore the mechanism of DEC2 deficiency promoting high incidence of post infectious cough(PIC)and the therapeutic effects of ephedrine hydrochloride(EH).Methods:C57BL/6 wild-type(WT)mice and DEC2-knockout(DEC2-KO)mice were treated with lipopolysaccharide(LPS)nose drops and smoke stimulation to establish PIC models,and some model mice were treated with EH intervention.Counting capsaicin-induced cough at 12,14,16 and 17 day of modeling;Single-cell sequenc-ing,flow cytometry,RT-qPCR and other techniques were used to detect the expressions of IL-1,IL-6,IFN-γ and other inflammatory factors and receptors in the lungs of mice before and after PIC modeling and EH intervention.The expressions of inflammatory factors and their receptors,as well as NF-κB signaling molecules,were analyzed by RT-qPCR using mouse lung CD45-primary cell culture system under LPS stimulation or EH intervention.Results:The transcription of DEC2 was increased in WT-PIC model mice,and the deficiency of DEC2 in DEC2-KO-PIC mice induced the cough frequency 2-fold higher than that in WT-PIC mice.The absence of DEC2 exacerbated LPS-induced pulmonary inflammatory response,especially increased expressions of IL-1,IL-6,IL-1Ra,IL-6Ra,IFN-γR in lung CD45-cells(P<0.01),and excessive activation of NF-κB signal(P<0.01).After EH treatment,the cough frequency in DEC2-KO-PIC mice was significantly reduced(P<0.001),the expression of IL-1,IL-6,IFN-γ in lung and IL-1Ra,IL-6Ra,IFN-γR in pulmonary CD45-cells were down-regulated(P<0.01).The expression and activation of NF-κB induced by DEC2 deletion were sig-nificantly inhibited(P<0.01).Conclusion:The deficiency of DEC2 can activate NF-κB signal and promote the high expression of in-flammatory cytokine and receptors in pulmonary CD45-cells,which is a risk factor in the high incidence of PIC.EH can inhibit the ex-cessive-activation of NF-κB signal and the inflammatory characteristics of lung local stromal cells caused by DEC2 absence,and that is the main part of pharmacological mechanism for effective treatment of EH targeting PIC.

Healthy female rabbits aged 3.5 to 4.0 months were randomly divided into four groups:the white light group(control group A),the green light group(treatment group B),the red light group(treatment group C)and the blue light group(treatment group D)with 3 replicates in each group,and 12 rabbits in each replicate.The light intensity was set to 80 lx,and the light was 16 h per day for 6 days before artificial insemination.Three reproductive cycles were carried out to de-termine the reproductive performance of female rabbits under different light colors,such as the number of fetuses,total litter size,weaning litter weight and serum reproductive hormone content.The results showed that,according to the comprehensive statistics of three breeding cycles:(1)the melatonin levels in the green group and red group were significantly lower than those in white group(P＜0.01),and the green group was significantly lower than the blue group(P＜0.05);the levels of luteinizing hormone in green group and red group were significantly higher than those in white group(P＜0.01);the follicle stimulating hormone in the green group was significantly high-er than in white group(P＜0.05);the estradiol content in the green group was significantly higher than that in the white group and blue group(P＜0.01),and significantly higher than that in the red group(P＜0.05).(2)the conception rate of the group was significantly higher than that of the white group(P＜0.01),and significantly higher than that of the red group and blue group(P＜0.05).(3)the number of rabbits in the green group at 30 days of age was significantly higher than that in the red group and the blue group(P＜0.05),and the litter weight at 30 days of age was significantly higher than that in the red group and the blue group(P＜0.01),and significantly higher than that in the white group(P＜0.05).In conclusion,the LED light belt is controlled by a dynamic light control system,the light intensity is set to 80 lx,and the light is 16 h a day for 6 d before artificial insemination.Green light can reduce the serum melatonin of Fujian white rabbits,which has the best comprehensive effect on the same period of conception rate and reproductive performance of Fujian white rabbits.

Healthy female rabbits aged 3.5 to 4.0 months were randomly divided into four groups:the white light group(control group A),the green light group(treatment group B),the red light group(treatment group C)and the blue light group(treatment group D)with 3 replicates in each group,and 12 rabbits in each replicate.The light intensity was set to 80 lx,and the light was 16 h per day for 6 days before artificial insemination.Three reproductive cycles were carried out to de-termine the reproductive performance of female rabbits under different light colors,such as the number of fetuses,total litter size,weaning litter weight and serum reproductive hormone content.The results showed that,according to the comprehensive statistics of three breeding cycles:(1)the melatonin levels in the green group and red group were significantly lower than those in white group(P＜0.01),and the green group was significantly lower than the blue group(P＜0.05);the levels of luteinizing hormone in green group and red group were significantly higher than those in white group(P＜0.01);the follicle stimulating hormone in the green group was significantly high-er than in white group(P＜0.05);the estradiol content in the green group was significantly higher than that in the white group and blue group(P＜0.01),and significantly higher than that in the red group(P＜0.05).(2)the conception rate of the group was significantly higher than that of the white group(P＜0.01),and significantly higher than that of the red group and blue group(P＜0.05).(3)the number of rabbits in the green group at 30 days of age was significantly higher than that in the red group and the blue group(P＜0.05),and the litter weight at 30 days of age was significantly higher than that in the red group and the blue group(P＜0.01),and significantly higher than that in the white group(P＜0.05).In conclusion,the LED light belt is controlled by a dynamic light control system,the light intensity is set to 80 lx,and the light is 16 h a day for 6 d before artificial insemination.Green light can reduce the serum melatonin of Fujian white rabbits,which has the best comprehensive effect on the same period of conception rate and reproductive performance of Fujian white rabbits.