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.

Background Lung tissue fibrosis caused by exposure to free silica (SiO₂) dust is the core pathological feature of silicosis. Lipocalin-2 (LCN2), as a secreted glycoprotein, plays an important role in various inflammatory diseases, but its specific role in silicosis-induced inflammatory injury remains unclear. Objective To identify differentially expressed genes (DEGs) and enriched pathways in the lung tissues of rats with silicosis, and to explore the regulatory mechanism of LCN2 in silicosis inflammation. Methods Twenty specific pathogen-free male SD rats were randomly divided into a control group and a silicosis model group (n=10 per group). The silicosis model was established via a single intratracheal instillation of silicon dioxide (SiO₂) suspension (50 mg), while the control group received an equal volume of normal saline. In vitro, NR8383 cells were divided into a control group and a SiO₂ treatment group. Hematoxylin-eosin (HE) staining and Van Gieson (VG) staining were used to evaluate alveolar structure damage, inflammatory infiltration, and collagen deposition in the lung tissues. Transcriptomic sequencing was applied to screen for DEGs and enriched signaling pathways. Western blot was used to detect the protein expression of interleukin-6 (IL-6), E-cadherin (ECA), cluster of differentiation 36 (CD36), liver X receptor (LXR), ATP-binding cassette transporter A1 (ABCA1), and LCN2 in both rat lung tissues and NR8383 cells. Immunohistochemistry was used to further assess LCN2 expression and localization. Additionally, NR8383 cells were treated with the LCN2 inhibitor ZINC00640089 and assigned to four groups: control, ZINC00640089-only, SiO₂, and SiO₂+ZINC00640089. Western blot was used to evaluate the expression of LCN2, IL-6, and interleukin-1β (IL-1β). Results HE and VG staining revealed disorganized lung tissue structure, damaged alveolar walls, nodule formation, and increased collagen deposition in the silicosis model group compared to the controls. Transcriptomic analysis identified 2723 DEGs in the lung tissues of silicosis rats (312 down-regulated and 2411 up-regulated) with LCN2 expression being significantly up-regulated. These DEGs were primarily enriched in pathways related to the innate immune response, extracellular matrix (ECM)-receptor interaction, and inflammatory response. Immunohistochemical staining confirmed elevated LCN2 levels in the lung tissues of the model rats. Western blot demonstrated that the protein levels of IL-6, CD36, and LCN2 were significantly increased (P<0.05), whereas ABCA1 and ECA were significantly decreased in the silicosis group (P<0.05). Similarly, in SiO₂-treated NR8383 cells, IL-6, CD36, and LCN2 expressions significantly increased (P<0.05), while ABCA1 and LXR significantly decreased (P<0.05). Compared with the SiO₂ group, treatment with ZINC00640089 significantly reduced the expression levels of LCN2, IL-6, and IL-1β (P<0.05). Conclusion LCN2 is significantly upregulated in both the lung tissues of silicosis rats and SiO₂-treated NR8383 cells. Inhibiting LCN2 expression effectively reduces the SiO₂-induced inflammatory response, indicating that LCN2 serves as a potential therapeutic target for silicosis.

Background: Disorders of the blood-brain barrier (BBB) arising from diabetes mellitus are closely related to diabetic encephalopathy. Previous research has suggested that neuron-glia antigen 2 (NG2)-glia plays a key role in maintaining the integrity of the BBB. However, the mechanism by which NG2-glia regulates the diabetic BBB remains unclear. Methods: Type 2 diabetes mellitus (T2DM) db/db mice and db/m mice were used. Evans-Blue BBB permeability tests and transmission electron microscopy techniques were applied. Tight junction proteins were assessed by immunofluorescence and transmission electron microscopy. NG2-glia number and signaling pathways were evaluated by immunofluorescence. Detection of matrix metalloproteinase-9 (MMP-9) in serum was performed using enzyme-linked immunosorbent assay (ELISA). Results: In T2DM db/db mice, BBB permeability in the hippocampus significantly increased from 16 weeks of age, and the structure of tight junction proteins changed. The number of NG2-glia in the hippocampus of db/db mice increased around microvessels from 12 weeks of age. Concurrently, the expression of MMP-9 increased in the hippocampus with no change in serum. Sixteen- week-old db/db mice showed activation of the Wnt/β-catenin signaling in hippocampal NG2-glia. Treatment with XAV-939 improved structural and functional changes in the hippocampal BBB and reduced MMP-9 secretion by hippocampal NG2-glia in db/db mice. It was also found that the upregulation of β-catenin protein in NG2-glia in the hippocampus of 16-week-old db/db mice was significantly alleviated by treatment with XAV-939. Conclusion The results indicate that NG2-glia can lead to structural and functional disruption of the diabetic BBB by activating Wnt/β-catenin signaling, upregulating MMP-9, and degrading tight junction proteins.

ObjectiveTo investigate the association between single and combined exposure to arsenic （As）， mercury （Hg）， and cadmium （Cd） in urine and hearing loss in adults. MethodsA total of 400 adult patients were recruited for the study， comprising 200 participants in the normal hearing group and 200 in the hearing loss group. General demographic information of the study subjects was collected by a self-administered questionnaire， morning urine samples were tested for As， Hg， and Cd concentrations， and hearing status was assessed by Pure Tone Audiometry. A binary Logistic regression model was used to explore the association between the concentrations of the three metals in urine and hearing loss， and a Bayesian kernel-machine regression （BKMR） model was used to further explore the association between the concentrations of the three metal mixtures and hearing loss. ResultsAfter correction for urinary creatinine， As， Hg， and Cd concentrations were higher in the hearing loss group than those in the normal hearing group （P<0.05）. Binary Logistic regression indicated that concentrations of As， Hg， and Cd were positively associated with hearing loss， and the risk of hearing loss was significantly higher in the second quartile of Cd concentration compared to the first quartile （OR=2.000， 95%CI： 1.009-3.964）. BKMR modeling analysis showed that the combined exposure levels of As， Hg， and Cd significantly increased the risk of hearing loss， with Cd being the most important contributor （posterior inclusion probability=0.412）， and that there were potential interactions between As and Cd， and Cd and Hg. ConclusionCombined exposure to As， Hg， and Cd in urine is significantly associated with adult hearing loss， with Cd being the primary contributor in the exposure combination. The interactions between As and Cd， as well as Cd and Hg， may have adverse effects on hearing loss.

To summarise the clinical experience of Professor CHAO Enxiang in treating idiopathic pulmonary hemosiderosis （IPH） by staging from heat， phlegm， stasis and deficiency. It is believed that IPH has blood-heat and phlegm-stasis， and deficiency of qi and yin as the core pathomechanisms， in which the pathomechanism of acute pulmonary haemorrhage is based on intense blood heat， and modified Shihui Powder （十灰散） is used to clear heat and regulate ying qi （nutrient qi）， and reduce fire to settle the collaterals. The pathomechanism of pulmonary haemorrhage in the static stage is based on phlegm-heat obstructing the lungs， and modified Qingfei Dingke Decoction （清肺定咳汤） is used to clear the lungs and dissolve phlegm， harmonize the collaterals to stop haemorrhage. The pathomechanism of acute exacerbation at chronic stage is based on deficiency of qi and yin， and also blood-heat and phlegm-stasis， modified Shengmai Powder （生脉散）， Shihui Powder plus Qingfei Dingke Decoction should be used to benefit qi and nourish yin， clear heat， resolve phlegm and eliminate blood stasis. In the chronic prolongation period， the pathogenesis of the disease is based on the deficiency of qi and yin， modified Shengmai Powder may be used to benefit qi and nourish yin， moisten the lungs and rest blood.

Objective To explore the correlation between osteocalcin (OCN) and visceral fat area (VFA) in overweight/obese population. Methods The data of 297 overweight/obese people who underwent health examinations in Health Management Department of Second Affiliated Hospital of Xi'an Jiaotong University from August 2021 to August 2024 were analyzed. According to the VFA value measured by InBody, the subjects were divided into an excessive group (VFA ≥100 cm²) and a normal group (VFA<100 cm2). The baseline data, glucose metabolism indicators, lipid metabolism indicators and OCN were compared between the two groups. Binary logistic regression analysis was used to analyze the independent risk factors affecting visceral fat deposition in overweight/obese people. Results According to the VFA value, there were 193 cases (64.98%) in the excessive group and 104 cases (35.02%) in the normal group. There were no statistical differences in gender, age and comorbidities between the two groups (P>0.05). The BMI, FPG, HbA1c, TC, TG, and LDL-C in the excessive group were higher than those in the normal group, while the HDL-C and OCN were lower than those in the normal group (P<0.05). Binary logistic regression analysis revealed that BMI, FPG, HbA1c, TC, TG and LDL-C were independent risk factors for visceral fat deposition in overweight/obese people, while HDL-C and OCN were protective factors (P<0.05). Conclusion Visceral fat deposition in overweight/obese people is closely related to OCN content, and is affected by abnormal glucolipid metabolism, which provides new ideas for the prevention and treatment of obesity-related diseases.

BACKGROUND: Currently, lung cancer is one of the malignant tumors with a high morbidity and mortality all over the world. However, the exact mechanisms underlying lung cancer progression remain unclear. The tumor necrosis factor receptor associated factor (TRAF) family members are cytoplasmic adaptor proteins, which function as both adaptor proteins and ubiquitin ligases to regulate diverse receptor signalings, leading to the activation of nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK) and interferon regulatory factor (IRF) signaling. The aim of this study was to investigate the expression of TRAFs in different tissues and cancer types, as well as its mRNA expression, protein expression, prognostic significance and functional enrichment analysis in non-small cell lung cancer (NSCLC), in order to provide new strategies for the diagnosis and treatment of NSCLC. METHODS: RNA sequencing data from the The Genotype-Tissue Expression database was used to analyze the expression patterns of TRAF family members in different human tissues. RNA sequencing data from the Cancer Cell Line Encyclopedia database was used to analyze the expression patterns of TRAF family members in different types of cancer cell lines. RNA sequencing data from the The Cancer Genome Atlas (TCGA) database was used to analyze the mRNA levels of TRAF family members across different types of human cancers. Immunohistochemistry (IHC) analyses from HPA database were used to analyze the TRAF protein levels in NSCLC [lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC)]. Overall survival analysis was performed by Log-rank test using original data from Kaplan-Meier Plotter database to evaluate the correlation between TRAF expressions and prognosis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on the TRAF family-related genes using RNA sequencing data from the TCGA database for NSCLC. The correlation between the expression levels of TRAF family members and the tumor immune microenvironment was analyzed using the ESTIMATE algorithm based on RNA sequencing data from the TCGA database. RESULTS: The TRAF family members exhibited significant tissue-specific expression heterogeneity. TRAF2, TRAF3, TRAF6 and TRAF7 were widely expressed in most tissues, while the expressions of TRAF1, TRAF4 and TRAF5 were restricted to specific tissues. The expressions of TRAF family members were highly specific among different types of cancer cell lines. In mRNA database of LUAD and LUSC, the expressions of TRAF2, TRAF4, TRAF5 and TRAF7 were significantly upregulated; while TRAF6 did the opposite; moveover, TRAF1 and TRAF3 only displayed a significant upregulation in LUAD and LUSC, respectively. Except for TRAF3, TRAF4 and TRAF7, other TRAF proteins displayed an obviously deeper IHC staining in LUAD and LUSC tissues compared with normal tissues. Additionally, patients with higher expression levels of TRAF2, TRAF4 and TRAF7 had shorter overall survival; while patients with higher expression levels of TRAF3, TRAF5 and TRAF6 had significantly longer overall survival; however, no significant difference had been observed between TRAF1 expression and the overall survival. TRAF family members differentially regulated multiple pathways, including NF-κB, immune response, cell adhesion and RNA splicing. The expression levels of TRAF family members were closely associated with immune cell infiltration and stromal cell content in the tumor immune microenvironment, with varying positive and negative correlations among different members. CONCLUSIONS TRAF family members exhibit highly specific expression differences across different tissues and cancer types. Most TRAF proteins exhibit upregulation at both mRNA and protein levels in NSCLC, whereas, only upregulated expressions of TRAF2, TRAF4 and TRAF7 predict worse prognosis. The TRAF family members regulate processes such as inflammation, immunity, adhesion and splicing, and influence the tumor immune microenvironment.
Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/mortality* ; Prognosis ; Gene Expression Regulation, Neoplastic ; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins/metabolism*

Objective:To analyze the relationship between the optimal surgical margin value and clinical prognosis of transoral robotic surgery（TORS） in treating human papillomavirus（HPV） -positive oropharyngeal squamous cell carcinoma. Methods:A single-center, prospective, observational cohort study was conducted, enrolling patients with early and moderated stage（≤T3 stage） oropharyngeal carcinoma undergoing TORS between July 2020 and April 2024. The proposed optimal surgical margin cutoff value for TORS was set as 2 mm. The primary objectives were to evaluate the optimal clear margin for TORS and its association with overall survival（OS） and progression-free survival（PFS）. Logistic regression was used to analyze correlations between surgical margins and clinical variables, while Cox regression models assessed the impact of surgical margins on OS and PFS. Results:A total of 90 patients（60 males, 66.7%） were included, all had squamous cell carcinoma, with a mean age of 58.0±9.0 years（range: 39-84 years） old. The 1, 2 and 3-year OS rates were 92.3%, 89.9% and 85.0%, respectively, while the 1, 2 and 3-year PFS rates were all 90.1%. For surgical margins ≤2 mm, the 1, 2 and 3-year OS rates were 80.8%, 69.3% and 69.3%, respectively, and PFS rates were 77.9% across three time points. For surgical margins>2 mm, the 1, 2 and 3-year OS rates were 96.5%, 96.5% and 90.6%, respectively, with PFS rates of 94.6%. Logistic regression showed no correlation between surgical margins and tumor type, T/N stage, smoking, alcohol use, or gender（P>0.05）. Cox analysis identified surgical margins>2 mm as a significant factor improving PFS（HR=0.14, 95%CI 0.02-0.90, P=0.038）. Conclusion:This systematic analysis suggests setting a 2 mm and longer as clear surgical margin for TORS. Margins>2 mm are associated with superior postoperative PFS rate and prolonged PFS time in HPV-positive oropharyngeal carcinoma patients.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Carcinoma, Squamous Cell/virology* ; Human Papillomavirus Viruses/isolation & purification* ; Margins of Excision ; Oropharyngeal Neoplasms/virology* ; Papillomavirus Infections/virology* ; Prognosis ; Prospective Studies ; Robotic Surgical Procedures/methods*

Objective To investigate the effects of Yiqi Wenyang Lishui Formula(derived from Wuling San combined with Astragali Radix and Descurainiae Semen Lepidii Semen)on cardiac function and remodeling in heart failure(HF)patients with yang deficiency and fluid retention syndrome and to analyze risk factors for influencing therapeutic efficacy.Methods A total of 120 HF patients with yang deficiency and fluid retention syndrome admitted to Liaocheng Hospital of Traditional Chinese Medicine from February 2022 to January 2024 were enrolled and randomly divided into observation group(n=60)and control group(n=60)using a random number table.The control group received conventional western therapy,while the observation group received Yiqi Wenyang Lishui Formula additionally.Both groups were treated for 2 months.Changes in cardiac function indicators and remodeling markers were observed.Clinical efficacy was evaluated,and univariate and binary logistic regression analyses were performed to identify independent risk factors affecting treatment outcomes.Results(1)The total effective rate was 81.67％(49/60)in the observation group versus 70.00％(42/60)in the control group.Intergroup comparison(by chi-square test)showed that the efficacy in the observation group was superior to the control group(P＜0.05).(2)After treatment,both groups showed significant reductions compared to those before treatment in left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(P＜0.01).The reduction in LVEDD,LVESD,and serum NT-proBNP levels in the observation group was significantly greater than that in the control group(P＜0.05 or P＜0.01).(3)Univariate analysis revealed that New York Heart Association(NYHA)functional classification,LVEDD,LVESD,and NT-proBNP levels were significantly associated with the therapeutic efficacy of the Yiqi Wenyang Lishui Formula in heart failure patients with yang deficiency and fluid retention syndrome(P＜0.05).(4)Logistic regression identified NYHA classification,LVEDD,LVESD,and NT-proBNP as independent risk factors(P＜0.05)in affecting therapeutic effect of Yiqi Wenyang Lishui Formula in treating HF with yang deficency and fluid retention syndrome,increasing the risk of ineffective treatment by 4.12-fold,1.21-fold,1.19-fold,and 1.00-fold,respectively.Conclusion Yiqi Wenyang Lishui Formula effectively improves cardiac function and remodeling in HF patients with yang deficiency and fluid retention syndrome.NYHA classification,LVEDD,LVESD,and NT-proBNP are independent risk factors for influencing efficacy,warranting close monitoring for optimized therapeutic adjustments.