BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

BACKGROUND:Several observational studies have found a strong association between thyroid function and its related disorders and osteoporosis,but the causal relationship is unclear.OBJECTIVE:To ascertain the causal relationship between genetically predicted thyroid function and its associated disorders,as well as osteoporosis,through the Mendelian randomization analysis with extensive pooled genetic data.METHODS:Pooled data from genome-wide association studies were employed to investigate the causal relationship between thyroid function and its associated disorders and osteoporosis.This was achieved through the utilization of the inverse variance weighting method as the primary Mendelian randomization analysis method,in conjunction with the MR-Egger method,weighted median method,simple model method,and weighted model method.A two-step mediated Mendelian randomization analysis was used to calculate the mediating effect of drug-mediated thyroid dysfunction on osteoporosis and the mediating proportion.Subsequently,sensitivity analyses were conducted using the MR-Egger intercept test and MR-PRESSO to detect multiplicity,Cochran's Q test to detect heterogeneity,and leave-one-out to perform sensitivity analyses.RESULTS AND CONCLUSION:(1)The results of the inverse variance weighting method showed that thyroid function had an effect on bone mineral density,and that thyrotropin,free triiodothyronine on bone mineral density,free thyroxine,and subclinical hyperthyroidism all had a causal effect on bone mineral density.(2)In addition,mediation analyses revealed a potential mediating effect of carbimazole in the causal relationship between hyperthyroidism and the risk of developing osteoporosis,as well as a potential mediating effect of levothyroxine sodium in the causal relationship between hypothyroidism and the risk of developing osteoporosis.(3)In conclusion,thyrotropin,which is high in the normal range,has been demonstrated to increase bone mineral density.Conversely,free triiodothyronine and free thyroxine,which are also high within the normal range,as well as subclinical hyperthyroidism,have been shown to decrease bone mineral density.The risk of developing osteoporosis is partially mediated by the pathway of taking the therapeutic medication in the context of pharmacologic treatment of thyroid dysfunction.(4)The present study primarily focuses on European population data.However,given the commonality of the genetic background and the generalizability of genome-wide data analysis methods,it is of significant importance to explore the pathogenesis of osteoporosis in the Chinese population,develop effective interventions,and provide genetic counseling.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Total laryngectomy is a crucial surgical intervention for patients with advanced malignant tumors of the larynx and nasopharynx. Despite its effectiveness, this procedure permanently severs the connection between the nasal cavity and the lower respiratory tract, leading to the cessation of nasal airflow. This disruption significantly impairs the patient's sense of smell and adversely affects their quality of life. Although olfactory loss is common in these patients, the assessment and rehabilitation of their olfactory function are often overlooked. This article reviews relevant literature on evaluating olfactory function and rehabilitation methods following total laryngectomy, with the aim of providing a theoretical foundation to enhance olfactory rehabilitation and overall quality of life for these patients.
Humans ; Laryngectomy/rehabilitation* ; Quality of Life ; Smell ; Laryngeal Neoplasms/surgery* ; Olfaction Disorders/etiology*

Objective:To explore the related risk factors of neonatal necrotizing enterocolitis (NEC) by constructing and comparing nine regression models.Methods:All NEC patients admitted to the neonatal internal medicine department, neonatal surgery department, and neonatal intensive care unit of Shanxi Provincial Children's Hospital (Shanxi Provincial Maternity and Child Health Center) from 2020 to 2022 were included as the case group. A control group consisted of children admitted during the same period based on the inclusion and exclusion criteria. The NEC data collected were used for feature selection by using the Boruta algorithm. Logistic regression, multi-decision tree gradient boosting, efficient gradient one-sided sampling, random forest, decision tree, gradient boosting decision tree (GBDT), neural network, support vector machine, and K-nearest neighbor models were constructed. The optimal model was selected through rigorous comparison and Shap explainable analysis was performed on the GBDT model.Results:Thirteen key factors were identified through screening for nine regression models construction. After strict comparison and analysis, the GBDT model showed higher stability compared with other eight regression models. In the validation set, the area under the receiver operating characteristic curve of the GBDT model was 0.958, with an accuracy of 0.925, and sensitivity and specificity of 0.827 and 0.950, respectively. Shap explainable analysis on the GBDT model revealed that suffering from anemia, non-invasive ventilator use, procalcitonin use, premature birth, and low birth weight increased the risk for NEC, while breastfeeding and probiotics decreased the risk for NEC.Conclusion:This study identified the risk factors and protective factors for NEC by using the GBDT model, which provided evidnce for the prevention and treatment of NEC.

Osteoporosis （OP） is a metabolic disorder characterized by microstructural deterioration of bone and increased bone fragility due to reduced bone mass， which can cause the development of bone-related diseases. This condition imposes significant economic and psychological burdens on patients. While modern medicine has extensively researched the pathogenesis of OP， it remains incompletely understood. Current clinical management primarily relies on anti-resorptive drugs and synthetic metabolic agents. However， long-term use of some medications may yield suboptimal therapeutic outcomes and lead to severe adverse reactions. Given the necessity for prolonged or lifelong treatment for OP， there is a critical need to identify highly effective， safe， and cost-effective pharmaceutical interventions. In light of evolving disease management paradigms and recent advancements in OP research， traditional Chinese medicine has demonstrated emerging advantages in addressing this condition. Through literature review， this study delves into the pathogenesis of OP from five perspectives： hormonal dysregulation， autophagy， ferroptosis， oxidative stress， and intestinal flora alteration. Furthermore， it summarizes the therapeutic efficacy and specific mechanisms of traditional Chinese medicine monomers and compound formulas against OP through regulating hormone levels， interfering with autophagy， inhibiting ferroptosis， counteract oxidative stress，and maintain intestinal flora balance. These multifaceted insights are expected to provide theoretical reference and guide future clinical traditional Chinese medicine approaches for preventing and managing OP.

Objective To investigate the therapeutic potential of human umbilical cord-derived mesenchymal stem cells(hUCMSCs)in modulating the cGAS-STING-NF-κB signaling pathway in chronic intermittent hypoxia(CIH)mice.Methods Twenty-four C57BL/6 mice were divided into the control group,the model group,the hUCMSCs group and the hUCMSCs+STING agonist(DMXAA)group,with 6 mice in each group.Except for the control group,the other groups were exposed to hypoxic conditions for 8 hours daily for a total of 8 weeks to establish the CIH mouse model.After 8 weeks,mice were anesthetized for cardiac blood collection followed by euthanasia and lung tissue collection.Serum levels of IL-6,TNF-α,IL-1β and IL-17A were measured by ELISA.Pulmonary inflammatory infiltration and collagen deposition were assessed by HE and Masson staining.E-Cadherin and α-SMA expression levels were evaluated by immunohistochemistry.Expression levels of cGAS,STING and NF-κB mRNA were detected by RT-qPCR,while protein expression levels of E-Cadherin,N-Cadherin,α-SMA,Vimentin,cGAS,STING and NF-κB were analyzed by Western blot assay.Results Compared with the control group,levels of IL-6,IL-1β,TNF-α and IL-17A increased in the model group,inflammation and fibrosis scores increased,mRNA expression levels of cGAS,STING and NF-κB increased,and protein expression levels of N-Cadherin,α-SMA,Vimentin,cGAS,STING and NF-κB increased.In contrast,E-Cadherin protein expression was significantly decreased(P＜0.05).Compared with the model group,IL-6,IL-1β,TNF-α and IL-17A decreased in the hUCMSCs group,mRNA expression levels of cGAS,STING and NF-κB were decreased,protein expression levels of N-Cadherin,α-SMA,Vimentin,cGAS,STING and NF-κB were also decreased.Meanwhile,E-Cadherin protein expression was significantly increased(P＜0.05).STING activator DMXAA reversed the protective effects of hUCMSCs in CIH mice(P＜0.05).Conclusion Intravenous administration of hUCMSCs alleviates pulmonary inflammatory infiltration and epithelial-mesenchymal transition in mouse model of intermittent hypoxia,which may be related to the down-regulation of the cGAS-STING-NF-κBsignaling pathway.

BACKGROUND:In recent years,a number of studies have confirmed that gut microbiome regulates bone metabolism through multiple pathways,and this field has become a research hotspot in orthopedics and microbiology.However,there is still no literature metrology and visual analysis on this field.OBJECTIVE:To explore the research status,hot spots and development trends in the field of gut microbiome regulation of bone metabolism,and to provide certain data support and reference for subsequent studies.METHODS:The Web of Science core collection database was used as the retrieval platform to retrieve the related literature in the field of intestinal flora regulating bone metabolism from 2004 to 2024.Citespace software was used to visually analyze the included literature and generate a visual atlas.RESULTS AND CONCLUSION:(1)A total of 1,035 papers were included in this study.In the past 20 years,the number of publications in the field of gut microbiome regulation of bone metabolism has shown a significant growth trend,with the United States and China dominating research and publication activities in this field.Harvard University and the University of California system are the research institutions with the highest number of published papers and research centrality in this area,and Professor Pacifici R of Emory University is the most prolific author.(2)Inflammatory bowel disease,chain fatty acids,bone marrow are the core keywords in this field.Postmenopausal osteoporosis,rheumatoid arthritis,oxidative stress,mitochondrial dysfunction are the latest research frontiers in this field.(3)Among the top 10 cited papers,4 discussed the mechanism of short-chain fatty acids affecting bone metabolism;3 investigated the pathogenesis and therapeutic potential of intestinal flora in postmenopausal osteoporosis,glucocorticoid-induced osteoporosis,and senile osteoporosis;1 discussed the relationship between intestinal inflammation,intestinal flora,parathyroid hormone,and bone metabolism;and 1 examined the effects of Lactobacillus rhamnosus and T cells on the gut microbiome and bone metabolism.(4)NUTRIENTS has the most papers,while ENDOCRINOLOGY& METABOLISM has the most citations.(5)Based on literature co-citation analysis and keywords,further exploration is needed on the specific pathogenesis and treatment strategies of gut microbiome in postmenopausal osteoporosis and rheumatoid arthritis,revealing the molecular mechanism of regulating gut microbiota to inhibit oxidative stress and improve mitochondrial dysfunction affecting bone metabolism,and translating mechanism research into clinical application,which all constitute the future research directions and trends in this field.

Objective To construct a prediction model for the risk of peripherally inserted central venous catheter(PICC)-related bloodstream infection(CRBSI)in preterm infants,and evaluate the effect of the model.Methods 1 295 preterm infants admitted to the neonatal intensive care unit(NICU)in a hospital and received PICC intrave-nous infusion from January 2019 to October 2023 were selected as the study subjects,including 1 080 preterm in-fants from January 2019 to December 2022 in the modeling set and 215 premature infants from January to October 2023 in the validation set.Risk factors of cases were analyzed based on 24 clinical characteristics,optimized charac-teristics was selected by LASSO regression,independent risk factors for CRBSI of preterm infants during PICC in-dwelling period were identified by multiple logistic regression analysis,and nomogram model was constructed with R software.Discrimination and fitting of the model were evaluated by the area under the curve(AUC)of the receiver operating characteristic(ROC)as well as Hosmer-Lemeshow test and calibration curve,and clinical practicality of the model was evaluated by decision curve analysis(DCA).Results Multivariate logistic analysis showed that birth weight ≥1 500 g,sterile protection during catheter maintenance,and sterile cloth wrapped joints were protective factors for CRBSI during PICC indwelling period in preterm infants(OR=0.172,0.187,0.063,respectively,all P＜0.05),while puncture frequency＞2 times,catheter indwelling period＞14 days,and use of tees were inde-pendent risk factors for CRBSI during PICC indwelling period in premature infants(OR=2.533,14.128,13.256,respectively,all P＜0.05).The AUC of ROC of the modeling set was 0.953(95％CI:0.936-0.969),and that of the validation set was 0.930(95％CI:0.885-0.974),indicating good discriminability of the model.The calibra-tion curve and Hosmer-Lemeshow goodness of fit test showed that the model had good accuracy and consistency,with high net profit value,indicating that the predictive value of the model was high and with good clinical practica-lity.The statistical test result in the rationality analysis of the model was P＜0.001.Conclusion The nomogram model based on the general clinical characteristics of preterm infants as well as the basic prevention and control measures of the catheter can provide a visual and simple evaluation tool for early identification of high risk factors for CRBSI in preterm infants.

Objective To develop a predictive model integrating clinical features,deep learning(DL),and radiomics based on T2-weighted imaging for prenatal assessment of postpartum hemorrhage(PPH)risk in high-risk pregnant women.Methods A total of 538 pregnant women with ultrasound-reported high-risk placenta accrete were retrospectively enrolled and divided into training,internal test,and external test cohorts.A nnUNet model was trained for automatic placental segmentation.Univariate and multivariate analyses were conducted on clinical features to identify those associated with PPH.Quantitative radiomic features were extracted from the placental region,and a random forest model was developed to predict estimated blood loss(EBL)and PPH risk.A DenseNet-based multi-task DL model was trained to predict PPH risk,EBL,and placenta previa status.Finally,a DL-radiomics ensemble(DRE)model was constructed by integrating clinical features,DL outputs,and radiomics scores.Diagnostic performance was evaluated using the area under the receiver operating characteristic curve(AUC)and DeLong test.Results The DRE model achieved AUC values of 0.874(95%CI:0.792-0.951)and 0.836(95%CI:0.648-0.974)in the internal and external test cohorts,respectively,significantly outperforming the standalone clinical,DL,and radiomics models.Incorporation of EBL regression improved the performance of the PPH classification model,with the external test AUC increasing from 0.261-0.788 to 0.836.Conclusion The DRE model integrating DL and radiomics can efficiently predict PPH risk and assist in the clinical management of high-risk pregnancies.