Objective: To investigate the reciprocal causal relationships between periodontitis and hepatobiliary diseases through Mendelian randomization (MR) analyses, to provide evidence for joint prevention and clinical decision-making in patients with concurrent periodontitis and hepatobiliary diseases. Methods: Single nucleotide polymorphisms (SNPs) were extracted from the largest genome-wide association study on periodontitis (17 353 cases, 28 210 controls) and hepatobiliary diseases within the European ancestry and used as instrumental variables (IVs). The strength of the associations was examined by calculating the F-statistic. The SNPs significantly associated with the outcome were removed by scanning on Phenoscanner platform. Bidirectional causal associations between periodontitis and hepatobiliary diseases were estimated using inverse variance weighted (IVW), MR-Egger, and Weighted Median methods. The robustness of the findings was further verified through additional sensitive MR approaches, including Cochran’s Q statistic （IVW）, Rucker’s Q statistic （MR-Egger）, MR-PRESSO and Leave-one-out analysis. Further MR analyses, utilizing other available genome-wide association studies (GWAS) on hepatobiliary diseases, were conducted to validate the results. Results: The IVW method found that periodontitis had a causal impact on acalculous cholecystitis (odds ratio = 1.277, 95% CI 1.097-1.485, P=0.002), implying an increased risk of acalculous cholecystitis associated with periodontitis, while the MR-Egger regression and Weighted Median failed to observe significant causal effects of periodontitis on acalculous cholecystitis. However, no bidirectional causal associations between periodontitis and nonalcoholic fatty liver disease, cirrhosis or liver cancer were observed using IVW, MR-Egger regression and Weighted Median. The bidirectional causal relationships were deemed unlikely to be influenced by horizontal pleiotropy. Further, the validation analysis based on alternative GWAS data suggested parallel results. Conclusions The MR analyses suggest that periodontitis may elevate the risk of acalculous cholecystitis. Further investigations, including clinical studies and mechanistic explorations, are warranted to validate these findings. However, the MR analyses do not support bidirectional causal associations between periodontitis and nonalcoholic fatty liver disease, cirrhosis or liver cancer.

Objective To investigate the causal relationship between circadian rhythm disruption and inflammatory bowel disease(IBD)and the mediating effect of gut microbiota based on Mendelian randomization(MR).Methods Summary statistics of Genome-wide Association Study(GWAS)for circadian rhythm disruption(n=205 527)and IBD(n=214 053)were obtained from IEU OpenGWAS database.Summary statistics of GWAS for the gut microbiota were obtained from the MiBioGen database(n=18 340).Two-sample MR analysis was used to estimate the genetic correlation and causality between circadian rhythm disruption and IBD,and the mediating effect of the gut microbiota was analyzed by two-step MR analysis.Results There was a suggestive causal relationship between circadian rhythm disruption and IBD(odds ratio=1.255,P＜0.05).Rikenellaceae id.967 played a mediating role in the causal chain between them(the mediating effect was-0.028 740).Sensitivity analysis confirmed that the results were not interfered by level pleiotropy and heterogeneity.Conclusion There is a genetic correlation between circadian rhythm disruption and IBD,and gut microbiota may play a mediating role between them.

Objective:To investigate the transcriptomic signature of refractory nasal polyps (NP) after endoscopic sinus surgery.Methods:Tissue samples were collected from 36 patients with NP who underwent endoscopic sinus surgery at the Seventh Affiliated Hospital of Sun Yat-sen University and the First Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021. Raw sequencing data of normal nasal mucosa samples were downloaded from publicly available GEO database (Accession Number: GSE136825). Differential expression genes (DEGs) and Gene Ontology (GO) enrichment analysis were conducted to analyze the differences between refractory NP and normal controls, as well as among refractory, controlled, and partially controlled NP. Hierarchical clustering method was employed to analyze the inflammatory endotypes of NP. Weighted Gene Co-expression Network Analysis (WGCNA) and STRING database were used in combination with Cytoscape software to identify the characteristic transcriptional expression profiles of refractory NP. R software (version 4.3.1) was used for statistical analysis.Results:Refractory NP patients had significantly higher asthma comorbidity rates than controlled/partially controlled groups ( P<0.05). The numbers and percentages of peripheral blood and tissue eosinophilic granulocytes were significantly higher in the refractory subgroup than in the other two subgroups ( P<0.05). Compared to normal mucosa, controlled and partially controlled NP groups, 27 genes were consistently upregulated in refractory NP. Hierarchical cluster analysis showed that the refractory NP exhibited a mixed endotype dominated by type 2 inflammation with co-existing type 1 features. Differential genes were enriched in extracellular matrix organization, leukocyte activation, cytokine receptor activation, cystatin-mediated protease inhibition, granule exocytosis, and olfactory nerve development regulation. Further WGCNA analysis and protein-protein interaction network identified 33 hub genes represented by ITGAM, NCF1, NCF2, CD1C, PTAFR, CLEC10A, SIRPA, TREM2, ALOX5AP, PTGDR2 (officially PTGDR), F13A1, DUOX2, NOS2, CTSG, and SALL1.Conclusion:This study reveals the distinctive transcriptional signature of refractory NP through transcriptomic methods, providing novel research avenues and therapeutic targets for the treatment of refractory NP after surgery.

Objective To develop and validate a prediction model to identify high-risk individuals who are at-risk to develop acute liver injury(ALI)within 180 days in new statin users,and to support early clinical intervention.Methods Data were sourced from the Yinzhou Regional Health Information Platform,covering statin initiators aged 18 years and older from January 1,2010,to October 31,2021.The dataset was divided into a derivation cohort and a temporal validation cohort based on the time of statin initiation.Predictors were selected using LASSO regression,and the model was constructed using the extreme gradient boosting(XGBoost)algorithm combined with cost-sensitive learning.Model performance was evaluated using Brier scores,Harrell's C-index,and calibration curves.Results A total of 126,440 statin initiators were included,with 90,542 in the derivation cohort and 35,898 in the validation cohort.Within 180 days of initial statin use,412(0.33％)patients developed ALI,including 305(0.34％)in the derivation cohort and 107(0.30％)in the validation cohort.The final model incorporated 16 predictors,which included demographic characteristics,lifestyle factors,family history,medical history,statin use,and concomitant medication use.The model demonstrated excellent overall performance[Brier score=0.0043,95％CI(0.0038,0.0049)],discrimination[Harrell's C-index=0.761,95％CI(0.725,0.794)],and calibration in internal validation.In temporal validation,the model also performed well[Brier score=0.0044,95％CI(0.0036,0.0052),Harrell's C-index=0.703,95％CI(0.614,0.781)].Conclusion This study develope and validate a prediction model for ALI in statin users,providing clinicians with a reliable tool for individualized risk assessment.This model can help achieve risk stratification and reduce the occurrence of ALI.

Objective To develop and validate a prediction model to identify high-risk individuals who are at-risk to develop acute liver injury(ALI)within 180 days in new statin users,and to support early clinical intervention.Methods Data were sourced from the Yinzhou Regional Health Information Platform,covering statin initiators aged 18 years and older from January 1,2010,to October 31,2021.The dataset was divided into a derivation cohort and a temporal validation cohort based on the time of statin initiation.Predictors were selected using LASSO regression,and the model was constructed using the extreme gradient boosting(XGBoost)algorithm combined with cost-sensitive learning.Model performance was evaluated using Brier scores,Harrell's C-index,and calibration curves.Results A total of 126,440 statin initiators were included,with 90,542 in the derivation cohort and 35,898 in the validation cohort.Within 180 days of initial statin use,412(0.33％)patients developed ALI,including 305(0.34％)in the derivation cohort and 107(0.30％)in the validation cohort.The final model incorporated 16 predictors,which included demographic characteristics,lifestyle factors,family history,medical history,statin use,and concomitant medication use.The model demonstrated excellent overall performance[Brier score=0.0043,95％CI(0.0038,0.0049)],discrimination[Harrell's C-index=0.761,95％CI(0.725,0.794)],and calibration in internal validation.In temporal validation,the model also performed well[Brier score=0.0044,95％CI(0.0036,0.0052),Harrell's C-index=0.703,95％CI(0.614,0.781)].Conclusion This study develope and validate a prediction model for ALI in statin users,providing clinicians with a reliable tool for individualized risk assessment.This model can help achieve risk stratification and reduce the occurrence of ALI.

Objective:To investigate the transcriptomic signature of refractory nasal polyps (NP) after endoscopic sinus surgery.Methods:Tissue samples were collected from 36 patients with NP who underwent endoscopic sinus surgery at the Seventh Affiliated Hospital of Sun Yat-sen University and the First Affiliated Hospital of Sun Yat-sen University from January 2020 to December 2021. Raw sequencing data of normal nasal mucosa samples were downloaded from publicly available GEO database (Accession Number: GSE136825). Differential expression genes (DEGs) and Gene Ontology (GO) enrichment analysis were conducted to analyze the differences between refractory NP and normal controls, as well as among refractory, controlled, and partially controlled NP. Hierarchical clustering method was employed to analyze the inflammatory endotypes of NP. Weighted Gene Co-expression Network Analysis (WGCNA) and STRING database were used in combination with Cytoscape software to identify the characteristic transcriptional expression profiles of refractory NP. R software (version 4.3.1) was used for statistical analysis.Results:Refractory NP patients had significantly higher asthma comorbidity rates than controlled/partially controlled groups ( P<0.05). The numbers and percentages of peripheral blood and tissue eosinophilic granulocytes were significantly higher in the refractory subgroup than in the other two subgroups ( P<0.05). Compared to normal mucosa, controlled and partially controlled NP groups, 27 genes were consistently upregulated in refractory NP. Hierarchical cluster analysis showed that the refractory NP exhibited a mixed endotype dominated by type 2 inflammation with co-existing type 1 features. Differential genes were enriched in extracellular matrix organization, leukocyte activation, cytokine receptor activation, cystatin-mediated protease inhibition, granule exocytosis, and olfactory nerve development regulation. Further WGCNA analysis and protein-protein interaction network identified 33 hub genes represented by ITGAM, NCF1, NCF2, CD1C, PTAFR, CLEC10A, SIRPA, TREM2, ALOX5AP, PTGDR2 (officially PTGDR), F13A1, DUOX2, NOS2, CTSG, and SALL1.Conclusion:This study reveals the distinctive transcriptional signature of refractory NP through transcriptomic methods, providing novel research avenues and therapeutic targets for the treatment of refractory NP after surgery.

Noise-induced hearing loss(NIHL)is a public health problem that requires immediate attention.Nearly one-third of hearing loss can be attributed to noise exposure.However,the molecular mechanism of NIHL is complex,and there is currently no specific drug available for preventing and treating NIHL.Therefore,it is particu-larly important to establish standardized preclinical research models of NIHL and identify molecular targets for treat-ment so as to carry out the prevention and drug treatment of NIHL effectively.In this article,we summarized the research methods and pharmacological treatment studies on NIHL to provide references for the prevention and treat-ment of NIHL.

Objective: To investigate the incidence density of adult sleep disorders (SD) in Yinzhou District, Ningbo City, Zhejiang Province from 2017 to 2023, so as to provide insights into formulating the control measures of SD. Methods: The electronic health records of permanent residents aged 18 years and over in Yinzhou District from 2017 to 2023 were collected through the Yinzhou Regional Health Information Platform. New cases of SD were diagnosed for the first time a year after establishing health records. The incidence density was estimated using Poisson distribution. The temporal, population and regional distribution characteristics of new cases of SD were analyzed using a descriptively epidemiological method. Results: From 2017 to 2023, there were 1 255 129 permanent residents aged 18 years and over in Yinzhou District, with a total observed person-time of 6 292 884 person-years and a median of 5.67 (interquartile range, 3.74) person-years. There were 165 490 new cases of SD, including 67 095 males (40.54%) and 98 385 females (59.46%). The incidence density of SD in Yinzhou District from 2017 to 2023 was 26.30/1 000 person-years, with no significant trend observed (P>0.05). The incidence density of SD was higher in females than in males (29.63/1 000 person-years vs. 22.57/1 000 person-years, P<0.05). The highest incidence density of SD was observed in individuals aged 70 to <80 years (63.30/1 000 person-years), and the lowest was in individuals aged 18 to <30 years (7.24/1 000 person-years). The incidence density of SD in individuals aged 30 years and over was higher than that in individuals aged 18 to <30 years (all P<0.05). The incidence density of SD was 32.03/1 000 person-years in individuals with junior high school education or below, which was higher than individuals with senior high school/technical secondary school education (25.93/1 000 person-years) and college degree and above (18.87/1 000 person-years, all P<0.05). Dongliu Street, Dongjiao Street, and Baihe Street had relatively higher incidence densities of SD, at 45.11/1 000 person-years, 42.87/1 000 person-years and 40.16/1 000 person-years, respectively. Conclusions From 2017 to 2023, there was no significant trend in the incidence density of SD in Yinzhou District. Higher incidence density were observed in females, the elderly, and individuals living in central urban areas.

Objective:To evaluate the predictive efficacy of sinus CT radiomics for treatment outcomes in nasal polyp patients undergoing endoscopic sinus surgery.Methods:A retrospective cohort study was conducted at the First Affiliated Hospital of Sun Yat-sen University, including 194 patients with nasal polyps treated between January 2015 and December 2019. The cohort comprised 132 males and 62 females, aged 16 to 75 years. Patients were divided into a training set ( n=135) and an internal validation set ( n=59). An external validation set ( n=34), consisting of 22 males and 12 females aged 16 to 59 years, was included from January 2020 to December 2021. Disease control was evaluated using the criteria from the European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS 2020). Radiomic features were extracted from sinus CT images and analyzed using the least absolute shrinkage and selection operator (LASSO) regression. Models combining radiomic and clinical features were developed to predict treatment efficacy. Results:The radiomics and combined models, based on four selected features, outperformed the clinical feature model in the training set, with AUC values of 0.901 and 0.915, versus 0.874, respectively. In the internal validation set, AUCs were 0.839, 0.832, and 0.716. Despite reduced AUCs in the external set, the radiomics model maintained good generalizability (0.748, 0.764, 0.620). Decision curve analysis showed significant clinical benefits in both radiomics and combined models.Conclusion:The CT-based radiomics model demonstrates significant predictive power in identifying refractory nasal polyps, suggesting its potential for clinical application in treatment outcome prediction.

Objective:To investigate the epidemiological characteristics of herpangina (HA) and its correlation with the incidence of hand, foot and mouth disease (HFMD) in children aged ≤6 years in Yinzhou District of Ningbo from 2017 to 2022.Methods:Epidemiological characteristics of HA in children aged ≤6 years were analyzed based on the electronic medical record data and public health management data from 2017 to 2022 collected from the Health Information Platform of Yinzhou. The incidence of HFMD was calculated using the infectious disease reporting data from the public health management data. Autoregressive integrated moving average model and cross-correlation function were used to evaluate the correlation between the incidence of HA and HFMD.Results:From 2017 to 2022, a total of 25 385 cases of HA were detected in children aged ≤6 years in Yinzhou, the male-to-female ratio of the cases was 1.12∶1. The average annual incidence of HA was 4 986.67/100 000, with the highest incidence in 2018 (10 477.09/100 000) and the lowest incidence in 2020 (870.88/100 000). The incidence peak of HA was during June to July. The incidence of HA was higher in age group 1 year (7 950.45/100 000) than in other age groups. The incidences of HA in Yunlong, Jiangshan and Xiaying were higher, with the incidence of 8 764.31/100 000, 8 377.58/100 000 and 7 965.31/100 000, respectively. The correlation coefficients between the incidence of HA and HFMD at lag day 0, 7, 12 and 18 were 0.199, 0.139, 0.090 and 0.086, respectively (all P<0.05). Conclusions:From 2017 to 2022, the incidence of HA was high in children aged ≤6 years in Yinzhou with obvious seasonality and area difference. The incidence of HA was correlated with the incidence of HFMD and the incidence of HFMD had certain lags. The comprehensive prevention and control of HA and HFMD should be further strengthened by prioritizing HA surveillance and implementing integrated surveillance and management of HA and HFMD.