Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

Inflammatory bowel disease (IBD) is an autoimmune disorder involving complex immune regulation, where balancing localized and systemic immunosuppression is a key challenge. This study aimed to enhance the therapeutic efficacy by engineering the probiotic Escherichia coli Nissle 1917 (EcN). We removed endogenous plasmids pMUT1 and pMUT2 from wild-type EcN and expressed the mPD-L1 (19‒238 aa)-mFc fusion protein on the bacterial surface using a cytolysin A (ClyA) fragment. This modification stabilized mPD-L1 (19‒238 aa) protein expression and promoted its recruitment to outer membrane vesicles (OMVs). The engineered strain, EcNΔ_pMUT1/2-ClyA-mPD-L1-mFc (EcN-ePD-L1-mFc), features conditional ePD-L1-mFc expression under the araBAD promoter, enhancing gut-targeted release and reducing systemic side effects. This strain improved treatment targeting and efficiency by enabling direct ePD-L1-mFc interaction with immune cells at inflammation sites. OMVs from this strain induced Treg proliferation, inhibited effector T cell proliferation in vitro, and significantly improved intestinal inflammation and colonic epithelial barrier repair in vivo. Additionally, the bacterium restored intestinal microbiota balance, increasing Lactobacillaceae and reducing Bacteroides. This study highlights the engineered bacterium's potential for targeted intestinal immune modulation and offers a novel local IBD treatment approach with promising clinical prospects.

Objective:To assess the impact of induction chemotherapy sensitivity on the prognosis and larynx preservation rates in patients with locally advanced hypopharyngeal cancer and to identify risk factors influencing induction chemotherapy sensitivity.Methods:This study included patients with locally advanced (stage III-IV) hypopharyngeal cancer who received induction chemotherapy as initial treatment at the Eye & ENT Hospital of Fudan University between August 2017 and September 2022. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, enrolled patients were classified into the sensitive group and the resistant group according to their response to induction chemotherapy. Chi-square tests and Log-rank tests were used to compare the objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and laryngeal preservation rate (LPR) between groups. Propensity score matching (PSM) was employed to accurately evaluate the impact of induction chemotherapy sensitivity on prognosis in real-world settings. Univariate and multivariate logistic regression analyses were performed to identify risk factors for induction chemotherapy resistance in locally advanced hypopharyngeal cancer.Results:A total of 197 patients with locally advanced hypopharyngeal cancer who received induction chemotherapy as initial treatment were included in, comprising 195 males and 2 females, with ages ranging from 36 to 74 years. Among them, 155 patients (78.68%) were classified into the sensitive group and 42 patients (21.32%) into the resistant group. The overall response rate (ORR) of induction chemotherapy in this cohort was 78.68%, with a five-year OS rate of 63.7%. The sensitive group had significantly better OS (mOS 6.32 vs. 5.05 year), PFS (mPFS 5.71 vs. 3.09 year) and a significantly higher LPR (91.6% vs. 69.0%) ( P<0.05). After propensity score matching, all covariates were balanced between the two groups, and the sensitive group showed significant improvement in OS ( P<0.05), while, no significant difference was observed in PFS and LPR between the two groups. Logistic regression analysis revealed that risk factors for induction chemotherapy failure in locally advanced hypopharyngeal cancer included: smoking status ( OR [95% CI]=4.751 [1.887-11.961]), tumor location in the posterior pharyngeal wall ( OR [95% CI]=2.988 [1.264-7.063]), and cN2-3 stage ( OR [95% CI]=3.641 [1.109-11.954]) ( P<0.05). Conclusions:Induction chemotherapy sensitivity significantly affects the prognosis of locally advanced hypopharyngeal cancer, which is influenced by various risk factors, including smoking status, tumor sublocation, and clinical N stage.

[Objective]To construct a prediction model for brucellosis by using a deep neural network algorithm to improve the early detection.[Methods]We collected the clinical data of 202 brucellosis patients and 319 non-brucellosis patients admitted to Hohhot Occupational Disease Prevention and Treatment Hospital in 2023,and analyzed data such as gender,age,blood routine indices and clinical diagnosis.A prediction model for brucellosis was constructed by using a deep neural network algorithm and optimized through 10-fold cross-validation.Performance metrics included sensitivity,false negative rate,specificity,false positive rate,accuracy,positive predictive value,negative predictive value,F1 score,and area under the receiver operating characteristic curve(AUC).The optimal model was interpreted by using SHapley Additive exPlanations(SHAP)to clarify decision-making logic and feature influencing mechanisms.[Results]Data visualization analysis revealed no significant difference between brucellosis and non-brucellosis groups.The optimal model demonstrated good performance:sensitivity(85.3%),specificity(92.1%),accuracy(89.5%),AUC(96.6%),95%CI(0.937,0.977).SHAP analysis identified age,platelet count,mean platelet volume,basophil ratio,red blood cell distribution width,and absolute basophil count as significant predictors of brucellosis.[Conclusions]The deep neural network prediction model constructed in this study has good performance and can provide reliable support for the early diagnosis,prevention and control of brucellosis.Identification of key brucellosis-related influencing features will help further understand the pathogenesis of the disease,and this model holds promise for broad clinical application in the future.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To assess the impact of induction chemotherapy sensitivity on the prognosis and larynx preservation rates in patients with locally advanced hypopharyngeal cancer and to identify risk factors influencing induction chemotherapy sensitivity.Methods:This study included patients with locally advanced (stage III-IV) hypopharyngeal cancer who received induction chemotherapy as initial treatment at the Eye & ENT Hospital of Fudan University between August 2017 and September 2022. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, enrolled patients were classified into the sensitive group and the resistant group according to their response to induction chemotherapy. Chi-square tests and Log-rank tests were used to compare the objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and laryngeal preservation rate (LPR) between groups. Propensity score matching (PSM) was employed to accurately evaluate the impact of induction chemotherapy sensitivity on prognosis in real-world settings. Univariate and multivariate logistic regression analyses were performed to identify risk factors for induction chemotherapy resistance in locally advanced hypopharyngeal cancer.Results:A total of 197 patients with locally advanced hypopharyngeal cancer who received induction chemotherapy as initial treatment were included in, comprising 195 males and 2 females, with ages ranging from 36 to 74 years. Among them, 155 patients (78.68%) were classified into the sensitive group and 42 patients (21.32%) into the resistant group. The overall response rate (ORR) of induction chemotherapy in this cohort was 78.68%, with a five-year OS rate of 63.7%. The sensitive group had significantly better OS (mOS 6.32 vs. 5.05 year), PFS (mPFS 5.71 vs. 3.09 year) and a significantly higher LPR (91.6% vs. 69.0%) ( P<0.05). After propensity score matching, all covariates were balanced between the two groups, and the sensitive group showed significant improvement in OS ( P<0.05), while, no significant difference was observed in PFS and LPR between the two groups. Logistic regression analysis revealed that risk factors for induction chemotherapy failure in locally advanced hypopharyngeal cancer included: smoking status ( OR [95% CI]=4.751 [1.887-11.961]), tumor location in the posterior pharyngeal wall ( OR [95% CI]=2.988 [1.264-7.063]), and cN2-3 stage ( OR [95% CI]=3.641 [1.109-11.954]) ( P<0.05). Conclusions:Induction chemotherapy sensitivity significantly affects the prognosis of locally advanced hypopharyngeal cancer, which is influenced by various risk factors, including smoking status, tumor sublocation, and clinical N stage.

[Objective]To construct a prediction model for brucellosis by using a deep neural network algorithm to improve the early detection.[Methods]We collected the clinical data of 202 brucellosis patients and 319 non-brucellosis patients admitted to Hohhot Occupational Disease Prevention and Treatment Hospital in 2023,and analyzed data such as gender,age,blood routine indices and clinical diagnosis.A prediction model for brucellosis was constructed by using a deep neural network algorithm and optimized through 10-fold cross-validation.Performance metrics included sensitivity,false negative rate,specificity,false positive rate,accuracy,positive predictive value,negative predictive value,F1 score,and area under the receiver operating characteristic curve(AUC).The optimal model was interpreted by using SHapley Additive exPlanations(SHAP)to clarify decision-making logic and feature influencing mechanisms.[Results]Data visualization analysis revealed no significant difference between brucellosis and non-brucellosis groups.The optimal model demonstrated good performance:sensitivity(85.3%),specificity(92.1%),accuracy(89.5%),AUC(96.6%),95%CI(0.937,0.977).SHAP analysis identified age,platelet count,mean platelet volume,basophil ratio,red blood cell distribution width,and absolute basophil count as significant predictors of brucellosis.[Conclusions]The deep neural network prediction model constructed in this study has good performance and can provide reliable support for the early diagnosis,prevention and control of brucellosis.Identification of key brucellosis-related influencing features will help further understand the pathogenesis of the disease,and this model holds promise for broad clinical application in the future.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

ObjectiveTo explore the distribution of pharyngeal microbiota in coal miners exposed to dust. Methods Eight coal miners who had been engaged in occupational dust exposure for more than 20 years were selected as the dust-exposed group, and four coal miners who were not exposed to dust at work were selected as the control group using the judgment sampling method. Pharyngeal secretions of the coal miners were collected with throat swabs, and its pharyngeal microbiota was analyzed. The diversity, abundance and evenness of the microbiota were analyzed by gene sequencing using the 16sRNA gene high-throughput sequencing technology. Results A total of 254 operational taxonomic units of pharyngeal microbiota were detected in the coal miners in the control group, which was 210 more than that in the dust-exposed group. The Chao1 index, Shannon index, PD-tree index and Pielou index of pharyngeal microbiota in the dust-exposed group decreased compared with the control group (all P<0.01). The abundance of Bacteroidetes and Clostridum, at the phylum level, in the pharynx of coal miners in the dust-exposed group was higher than that in the control group (all P<0.05). The abundance of Prevotella, Neisseria, and Monas, at the genus level, in the pharynx of coal miners in the dust-exposed group was higher than that in the control group(all P<0.05), while the abundance of Lactobacillus decreased (P<0.05). The analysis results of the receiver operating characteristic curve showed that Lactobacillus, Fusobacterium and Rothia may play a role for pharyngeal microbiota imbalance prediction in dust-exposed workers, and the area under the curves were all 1.00±0.00. Conclusion The species diversity and evenness of pharyngeal microbiota in coal miners exposed to dust are decreased, which may be related to the continuous inhalation of coal dust that disrupts the microbial environment of the throat.

Objective:To investigate the potential mechanism of miR-1298-5p in non-small cell lung cancer(NSCLC)to regu-late the MSH2 gene and its effect on the biological behavior of tumor cells and the tumor immune microenvironment.Methods:Bioin-formatics was used to identify the key genes and miRNA involved in NSCLC.Cell proliferation was detected by CCK-8 assay,and cell invasion and migration were detected by Transwell assay.Levels of inflammatory factors were detected by ELISA assay.Western blot was used to measure the expression of MSH2 in cells,and fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect the expressions of miR-1298-5p and MSH2 gene in NSCLC cells.Dual luciferase reporter gene assay was performed to verify the targeting relationship between miR-1298-5p and MSH2.Spearman correlation analysis was performed to correlate miR-1298-5p with immune cells and immune factors in the tumor immune microenvironment.Results:The level of miR-1298-5p was down-regulated in NSCLC cells compared with normal lung tissue cells.miR-1298-5p overexpression inhibited the proliferation,migration and inva-sion of NSCLC cells.MSH2 was confirmed to be a target gene of miR-1298-5p using luciferase reporter gene assay.Furthermore,down-regulation of miR-1298-5p in NSCLC cells could be reversed by silencing MSH2.miR-1298-5p expression levels were negatively corre-lated with the levels of Treg,IL-10,and TGF-β,and positively correlated with the levels of CD3+T,CD4+T,CD8+T,NK cells,IL-2,and IFN-γ.Conclusion:miR-1298-5p negatively regulates MSH2 to inhibit the proliferation,invasion and migration of NSCLC cells and improve the tumor immune microenvironment.