Noise-induced hearing loss is a worldwide public health issue that is characterized by temporary or permanent changes in hearing sensitivity. This condition is closely linked to inflammatory responses, and interventions targeting the inflammatory gene tumor necrosis factor-alpha (TNFα) are known to mitigate cochlear noise damage. TNFα-induced proteins (TNFAIPs) are a family of translucent acidic proteins, and TNFAIP6 has a notable association with inflammatory responses. To date, there have been few reports on TNFAIP6 levels in the inner ear. To elucidate the precise mechanism, we generated transgenic mouse models with conditional knockout of Tnfaip6 (Tnfaip6 cKO). Evaluation of hair cell morphology and function revealed no significant differences in hair cell numbers or ribbon synapses between Tnfaip6 cKO and wild-type mice. Moreover, there were no notable variations in hair cell numbers or hearing function in noisy environments. Our results indicate that Tnfaip6 does not have a substantial impact on the auditory system.
Animals ; Mice, Knockout ; Hair Cells, Auditory, Inner/pathology* ; Mice ; Mice, Transgenic ; Hearing Loss, Noise-Induced ; Evoked Potentials, Auditory, Brain Stem/physiology*

Cancer stem cells (CSCs) are widely acknowledged as primary mediators to the initiation and progression of tumors. The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years. Porphyromonas gingivalis (P. gingivalis) is increasingly considered to be closely related to the development of oral squamous cell carcinoma (OSCC). Nevertheless, the role of P. gingivalis in the stemness of OSCC cells remains uncertain. Herein, we showed that P. gingivalis was positively correlated with CSC markers expression in human OSCC specimens, promoted the stemness and tumorigenicity of OSCC cells, and enhanced tumor formation in nude mice. Mechanistically, P. gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1 (SCD1) expression, a key enzyme involved in lipid metabolism, which ultimately resulted in enhanced acquisition of stemness. Moreover, SCD1 suppression attenuated P. gingivalis-induced stemness of OSCC cells, including CSCs markers expression, sphere formation ability, chemoresistance, and tumor growth, in OSCC cells both in vitro and in vivo. Additionally, upregulation of SCD1 in P. gingivalis-infected OSCC cells was associated with the expression of KLF5, and that was modulated by P. gingivalis-activated NOD1 signaling. Taken together, these findings highlight the importance of SCD1-dependent lipid synthesis in P. gingivalis-induced stemness acquisition in OSCC cells, suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.
Porphyromonas gingivalis/pathogenicity* ; Stearoyl-CoA Desaturase/metabolism* ; Humans ; Carcinoma, Squamous Cell/pathology* ; Mouth Neoplasms/metabolism* ; Animals ; Neoplastic Stem Cells/microbiology* ; Mice, Nude ; Mice ; Nod1 Signaling Adaptor Protein/metabolism* ; Kruppel-Like Transcription Factors/metabolism* ; Cell Line, Tumor

Objective:To develop a multi-parameter diagnostic model for pediatric McCune-Albright syndrome(MAS) using machine learning techniques based on laboratory data from MAS patients, with the goal of providing a rapid and reliable auxiliary diagnostic tool for clinical practice.Methods:In this retrospective study, 232 children diagnosed with MAS at the Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from March 2023 to November 2024 were enrolled as the positive group. After removing duplicate or missing data, 119 cases were finally selected for statistical analysis as the positive group. Meanwhile, 113 children with normal physical examinations during the same period were selected as the control group. The clinical manifestations of the classic " triad" in the positive group were documented. Fasting serum samples were obtained from both groups at 8: 00 AM for laboratory testing, including bone metabolism-related and hormone-related indicators, which served as candidate features. Baseline descriptive analysis was conducted on the hormone-related indicators. For the bone metabolism indicators, six machine learning models—support vector machine(SVM), XGBoost, decision tree, random forest, Logistic regression, and K-nearest neighbor(KNN)—were constructed using R software. XGBoost subgroup analysis was performed based on the triad symptoms. The contribution of individual features to model predictions was visualized using SHAP diagrams. Results:SHAP visualization indicated that age, serum phosphorus, osteocalcin, and β-C-terminal cross-linked telopeptide of type Ⅰ collagen had the greatest average impact on model predictions. Among the six models, the SVM model achieved the highest diagnostic performance, with a sensitivity of 0.742 9, a specificity of 0.909 1, and an area under the curve (AUC) of 0.917.Conclusion:This study demonstrates that machine learning models, based on data from the positive patients and normal controls, can effectively distinguish MAS patients from healthy controls. The diagnostic model developed offers clinicians a valuable tool for early detection of MAS in children, contributing to earlier diagnosis, timely intervention, and improved clinical management.

McCune-Albright syndrome(MAS) is a postzygotic somatic mutation disorder caused by activating mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein. Its clinical features typically include polyostotic fibrous dysplasia, cafe-au-lait skin pigmentation, and endocrine hyperactivity, such as Cushing′s syndrome, hyperthyroidism, and growth hormone excess. Here, we report two rare cases of MAS complicated with adrenocorticotropic hormone(ACTH)-independent Cushing syndrome, and provide a review and analysis of previously reported MAS cases associated with Cushing′s syndrome.

Objective:To investigate the imaging characteristics of fibrous dysplasia(FD) in children with McCune-Albright syndrome(MAS) and the correlation between FD severity and bone metabolism markers, so as to provide a basis for clinical diagnosis and treatment.Methods:A total of 46 children(38 females and 8 males) with MAS with FD who were admitted to the Department of Pediatrics of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2016 were included in the retrospective study, and all of them met the diagnostic criteria for either the MAS triad or dual manifestations. The extent and characteristics of FD lesions were evaluated by imaging analysis(X-ray and CT). The distribution of café-au-lait spots and endocrine abnormalities were recorded. The serum bone metabolism levels [total procollagen type 1 amino-terminal propeptide(TP1NP), osteocalcin, β-C-terminal telopeptide(β-CTX), alkaline phosphatase(ALP)], and other related indicators such as calcium, phosphorus, magnesium, and fibroblast growth factor(FGF23) levels were detected, and the association between FD severity and indicators was evaluated by Spearman correlation analysis.Results:Among the 46 children, there were 24 cases of triad(FD+ café-au-lait spots + precocious puberty) and 22 cases of dual manifestations(11 cases of FD+ café-au-lait spots or precocious puberty). The age of onset of FD patients(24 cases) with bilateral long bones and skull FD was significantly earlier than that in the unilateral FD group [(3.33±1.34)years vs(5.26±2.34)years, P<0.01], and all of them had extensive café-au-lait spots across the midline. Polyostotic FD accounted for 71.7%(33/46), mainly cystic expansive lesions involving the femur(30 cases) and tibia(24 cases), and skull FD(25 cases) mostly showed ground-glass changes; Monostotic FD(13 cases) was more common in the skull(5 cases) and phalanges(5 cases). FD severity was significantly positively correlated with ALP( ρ=0.554, P=0.002), and negatively correlated with serum phosphorus( ρ=-0.522, P=0.006). All 6 children with severe fractures had FGF23-mediated hypophosphatemia [(1.03±0.12) mmol/L vs control(1.52±0.15) mmol/L, P=0.003]. Conclusions:Extensive café-au-lait spots(across the midline) in children with MAS are strongly associated with early-onset polyostotic FD; FD severity was strongly associated with bone turnover markers(TP1NP, β-CTX, ALP) and FGF23-mediated hypophosphatemia. Early comprehensive skeletal assessment and regular FGF23 monitoring are recommended for children with MAS presenting with extensive cutaneous café-au-lait spots.

Objective To explore the medication patterns of the"phlegm-stasis co-treatment"in the treatment of stroke and the regulatory mechanisms of its key components.Methods The relevant literature on the treatment of stroke with intertwined phlegm and blood stasis pattern by traditional Chinese medicine in CNKI,Wanfang Data Knowledge Service Platform and VIP was collected.Excel 2019 and SPSS Modeler 18.0 were applied to statistically analyze the nature,taste,meridian tropism and frequency of the drugs included in the prescriptions.The Apriori algorithm was used to perform association rule analysis and cluster analysis.The potential mechanism of action of the core drug pair was explored by using the network pharmacology method.Results A total of 69 prescriptions involving 161 herbs with 902 cumulative frequency uses were included.The four natures were mainly warm,neutral and cold,the five flavors were mainly bitter,sweet and pungent.and channel tropism were mainly liver meridian and spleen meridian.The analysis of association rules indicates that there was a strong correlation among chuanxiong,Taoren,Dannanxing,Dilong,Honghua,Shichangpu and Fuling.The main active components of the drug combination were quercetin,gallic acid,baicalein and hederagenin.They can regulate signaling pathways such as hypoxia-inducible factor-1,advanced glycation end product/advanced glycation end product receptor,nuclear factor κB,and mixed lineage kinase 3 by acting on genes such as STAT3,SRC,JUN,TP53,and MAPK1.Conclusion The core drugs of"phlegm-stasis co-treatment"method can act on multiple targets and pathways through components such as quercetin,gallic acid,baicalein and hederagenin,thereby exerting a therapeutic effect on stroke.

Objective:To investigate the association between blood selenium levels and sex hormones in Chinese men aged 18-79 years.Methods:Data were derived from the China National Human Biomonitoring survey conducted in 2017-2018, with a final sample size of 5 414 men. General demographic characteristics, behavioral habits, and dietary frequency were collected through questionnaires and physical examinations. Fasting blood samples were collected to measure blood lead, serum testosterone, and estradiol levels. Complex sampling linear regression models were used to analyze the associations between blood selenium levels and testosterone, estradiol, and the testosterone/estradiol ratio, adjusting for confounding factors including age, education level, marital status, smoking status, alcohol consumption, seafood intake, soy product intake, protein supplement intake, BMI, and diabetes status.Results:The mean age of the 5 414 participants was (46.85±27.91) years; 4 774 (91.65%) were of Han ethnicity and 4 505 (86.68%) were married. The median ( Q1, Q3) blood selenium concentration in men was 97.80 (80.64, 116.99) μg/L. After adjusting for confounding factors, the complex sampling linear regression model revealed negative associations between blood selenium levels and both testosterone levels and the testosterone/estradiol ratio, with a significant linear trend ( Ptrend<0.05). Compared with the Q1 group, the β (95% CI) values for testosterone in the Q2, Q3, and Q4 groups were -0.02 (-0.06 to 0.02), -0.03 (-0.08 to 0.01), and -0.06 (-0.09 to -0.02), respectively. Similarly, the β (95% CI) values for the testosterone/estradiol ratio in the Q2, Q3, and Q4 groups were -0.01 (-0.03 to 0.02), -0.01 (-0.04 to 0.04), and -0.03 (-0.06 to -0.01), respectively. Subgroup analysis indicated stronger associations between blood selenium levels and testosterone/estradiol levels in non-smoking and obese men (BMI≥28 kg/m2). Conclusion:Blood selenium levels are negatively associated with testosterone levels and the testosterone/estradiol ratio in Chinese adult males.

Objective:To explore the association of blood and urinary cadmium levels with lipid profile levels and dyslipidemia in Chinese adults aged 18 to 79 years.Methods:Based on the China National Human Biomonitoring (CNHBM) program, a cross-sectional survey was conducted from 2017 to 2018 using a multi-stage stratified random sampling method, including a total of 10 713 adults aged 18 to 79 years. Data was obtained through questionnaires, physical examinations, biological sample collection, and laboratory testing. Multiple linear mixed effect model (MLMM) and generalized linear mixed effect model (GLMM) were used to analyze the association of blood and creatinine-corrected urinary cadmium levels with lipid profile levels as well as dyslipidemia among adults.Results:The age of 10 713 participants was (47.23±0.24) years, with 5 372 males accounting for 61.3% of the national population. The weighted mean±standard error (SE) of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was (5.21±0.03), (1.86±0.03), (2.96±0.03), and (1.43±0.01) mmol/L, respectively. The prevalence rate of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, low HDL-C, and high LDL-C was 16.0%, 21.6%, 6.6%, 13.5%, and 10.0%, respectively. MLMM showed that, after adjusting for relevant confounders, log-transformed blood cadmium levels were positively associated with increased levels of TC, TG and LDL-C ( P<0.05). When blood cadmium levels were categorized into quartiles, compared to the lowest exposure group ( Q1), participants in the highest blood cadmium exposure group ( Q4) had increases of 0.19 (95% CI: 0.06, 0.32) mmol/L in TC and 0.25 (95% CI: 0.08, 0.43) mmol/L in TG. GLMM indicated that, after adjusting for confounders, higher blood cadmium exposure levels were associated with increased risks of hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and high LDL-C ( P<0.05). Further analysis by quartiles showed that, compared to the blood cadmium Q1 exposure group, the OR value (95% CI) for the Q4 group was 1.53 (1.12, 2.08) for hypercholesterolemia, 1.54 (1.09, 2.17) for hypertriglyceridemia, 2.24 (1.47, 3.40) for mixed hyperlipidemia, and 1.49 (1.07, 2.09) for high LDL-C. Conclusion:The cadmium internal exposure levels are associated with blood lipid profile levels as well as the incidence of dyslipidemia in Chinese adults aged 18 to 79.

[Purpose]To analyze the changes in the incidence trend of thyroid cancer from 1990 to 2021,and to predict the future incidence from 2022 to 2030.[Methods]We collected data related to the incidence of thyroid cancer among Chinese residents from 1990 to 2021 in the Global Bur-den of Disease 2021(GBD 2021)study,analyzed the trend of thyroid cancer incidence using the Joinpoint regression model,and constructed a Bayesian age-period-cohort(BAPC)model to pre-dict the future incidence of thyroid cancer during the years of 2022-2030,based on the inci-dence data during the years of 1990-2021.[Results]From 1990 to 2021,the age-standardized incidence rate(ASIR)of thyroid cancer in China showed a fluctuating upward trend,and the ASIR of thyroid cancer in China in 2021 was 2.47/105,slightly lower than the global average(2.91/105)in the same year.In 2021,there were significant differences in new cases and incidence rate of thyroid cancer between men and women,with the incidence rate of women being higher than that of men.Among them,the number of new cases in women was 27 915,the crude incidence rate was 4.02/105,and the ASIR was 2.87/105;in men,the number of new cases was 20 189,the crude incidence rate was 2.77/105,and the ASIR was 2.11/105.Between 1990 and 2021,the increase in the number of new cases,the crude incidence rate,and the ASIR of men in China was much larger than that of women.The ASIR of thyroid cancer in both male and female showed an in-creasing trend,while the average annual percentage change(AAPC)in female was lower than that in male.There were significant gender differences in the age-specific incidence rates of thyroid cancer.In 2021,the incidence rate of women was higher than that of men in the Chinese population＜75 years old,whereas the incidence rate of men was higher than that of women in the population≥75 years old.From 1990 to 2021,the incidence rates of the Chinese male population aged 45～59 years old and ≥75 years old increased significantly;and the incidence rate of the Chinese fe-male popu-lation aged 50～74 years old increased significantly.Projections showed that the ASIR of overall,male and female standardized incidence rates in 2030 increased to 2.90/105,2.44/105 and 3.26/105 respectively.[Conclusion]The incidence rate of thyroid cancer in China is on the rise,with the incidence rate of women being higher than that of men,but the incidence rate of men has increased more than that of women,and the gap between the incidence rates is narrow-ing,and the peak age of incidence of men is mostly in the senior age group.

Objective:To explore the challenges faced by ethical review in health care big data research and propose countermeasures, so as to provide a reference for the ethical review practice of such research.Methods:Based on the research of relevant domestic and foreign laws, regulations, literature, and other materials, combined with the work practice, analysis and summary were conducted.Results:Current ethics committees and research ethics guidelines are not applicable when dealing with health care big data research. Due to the lack of normative guidance, committees face challenges in assessing informed consent, privacy protection, and risk-benefit distribution of the research, and cross-institutional collaboration and data reuse are prone to be detached from review and supervision.Conclusions:It is urgent to construct and improve the review and supervision mechanism, innovate the informed consent model, and pay attention to the public interests and social values of research while effectively protecting the privacy of participants. In addition, it's important to promote the construction of multidisciplinary collaborative ability of ethics committees and supervise health care big data research by promoting the joint participation of stakeholders including the public.