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.

Methods: Cervical radiographs were analyzed. EOP hyperplasia was classified into three subtypes with standardized length measurements. Variables encompassed demographics, ONL-related indices, and sagittal parameters. Subtype comparisons and multivariate regression analyses (with EOP length as dependent variable) were conducted. Results: Analysis of 187 CSM patients (64.2% male) identified gender-specific patterns: males exhibited greater EOP length (9.4±6.8 mm vs. 4.6±3.4 mm, p<0.001). Type III EOP demonstrated male predominance (82.4% vs. type I 31.8%, type II 51.4%; p<0.001), with associated longer hyperplasia length (11.6±6.6 mm vs. type II 5.1±1.9 mm, p<0.001). Type III EOP was associated with higher ONL prevalence (type III 64.8% vs. type I 45.5%, type II 41.9%; p=0.010) and longer ONL osteophyte length (type III 18.8±9.8 mm vs. type I 14.2±8.1 mm, type II 14.2±9.4 mm; p=0.046). Multivariate regression confirmed male sex (β=–3.82, p=0.009), ONL osteophyte length (β=0.16, p=0.017), T1 slope (β=0.27, p=0.041), and spino-cranial angle (β=–0.19, p=0.009) as factors independently associated with EOP length (adjusted R²=0.382). Conclusions Severe EOP hyperplasia exhibits a male-predominant distribution pattern and demonstrates significant radiological associations with ONL and cervical sagittal imbalance in CSM patients. These findings advocate for EOP evaluation in clinical evaluations to identify high-risk biomechanical profiles.

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.

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.

ObjectiveTo explore the clinical safety of Feilike Mixture （FLK） in the real world. MethodsThe safety of all children who received FLK from 29 institutions in 12 provinces between January 21，2021 and December 25，2021 was evaluated through prospective centralized surveillance and a nested case control study. ResultsA total of 3 035 juveniles were included. There were 29 research centers involved，which are distributed across 12 provinces，including one traditional Chinese medicine （TCM） hospital and 28 general hospitals. The average age among the juveniles was （4.77±3.56） years old，and the average weight was （21.81±12.97） kg. Among them，119 cases （3.92%） of juveniles had a history of allergies. Acute bronchitis was the main diagnosis for juveniles，with 1 656 cases （54.46%）. FLK was first used in 2 016 cases （66.43%），and 142 juvenile patients had special dosages，accounting for 4.68%. Among them，92 adverse drug reactions （ADRs） occurred，including 73 cases of gastrointestinal system disorders，10 cases of metabolic and nutritional disorders，eight cases of skin and subcutaneous tissue diseases，two cases of vascular and lymphatic disorders，and one case of systemic diseases and various reactions at the administration site. The manifestations of ADRs were mainly diarrhea，stool discoloration，and vomiting，and no serious ADRs occurred. The results of multi-factor analysis indicated that special dosages （the use of FLK）［odds ratio （OR） of 2.642， 95% confidence interval （CI） of 1.105-6.323］，combined administration： spleen aminopeptide （OR of 4.978， 95%CI of 1.200-20.655），and reason for combined administration： anti-infection （OR of 1.814， 95%CI of 1.071-3.075） were the risk factors for ADRs caused by FLK. Conclusion92 ADRs occurred among 3 035 juveniles using FLK. The incidence of ADRs caused by FLK was 3.03%，and the severity was mainly mild or moderate. Generally，the prognosis was favorable after symptomatic treatment such as drug withdrawal or dosage reduction，suggesting that FLK has good clinical safety.

Objective:To study the effects of Linc00426 on the migration,invasion and proliferation of oral squamous carcinoma cells(OSCC).Methods:TCGA database was used to query the differential expression of Linc00426.RT-qPCR was used to detect the expression level of Linc00426 in normal human oral keratinocytes(NHOK)cells and various OSCC cells lines,the knockout effi-ciency of Linc00426 at 3 sites and the expression level of miR-455-5p.Transwell test and EdU test were used to detect the changes of the migration,invasion and proliferation of CAL27 cells.Bioinformatics databases was used to predict subcellular localization and downstream miRNAs and target proteins of Linc00426.Western blot assay was used to detect the changes of USP3 expression levels in CAL27 cells.Results:The expression level of Linc00426 was increased in OSCC tissue(P＜0.05),and its expression in CAL27,HN4 and HN30 cells was higher than that in NHOK cells(P＜0.05).Knocking out Linc00426 inhibited the migration,invasion,and proliferation ability of CAL27 cells(P＜0.05).The bioinformatics database indicates that the subcellular localization of Linc00426 is in the cytoplasm;Linc00426 is negatively correlated with miR-455-5p,and miR-455-5p is negatively correlated with USP3,in which there are targeted binding sites.Knocking out miR-455-5p promoted the migration,invasion and proliferation of CAL27 cells(P＜0.05).Knocking out USP3 inhibited the migration,invasion and proliferation of CAL27 cells(P＜0.05).Knock out Linc00426 reduced the expression level of USP3,while knocking out miR-455-5p increased the expression level of USP3(P＜0.05).Conclusion:Linc00426 plays a role as an oncogene in OSCC cells and could inhibit the migration,invasion and proliferation of the cells by targeting USP3 to regulate miR-455-5p.

Objective:To analyze the epidemic characteristics and changing trends of human brucellosis in Tangshan City, providing a basis for brucellosis prevention and control.Methods:Brucellosis surveillance data and historical surveillance data of Tangshan City reported from 2007 to 2022 in China Disease Prevention and Control Information System were collected. A descriptive analysis using retrospective methods was conducted to summarize the epidemic situation, distribution of three (population, time, region) and pathogenic monitoring results of brucellosis. Joinpoint regression was used to analyze the trend of brucellosis incidence.Results:From 2007 to 2022, a total of 3 949 cases of brucellosis were reported in Tangshan City, with the annual incidence ranging from 0.24 per 100 000 to 7.17 per 100 000, showing an upward trend (AAPC = 18.42%, 95% CI: 10.16% - 24.67%, P < 0.001). The affected population was mainly composed of those aged 40 - 69 years old (3 582 cases, accounting for 90.71%), male (2 957 cases, accounting for 74.88%), and farmers (3 432 cases, accounting for 86.91%). The onset time was mainly concentrated from March to August. The average annual incidence rates of brucellosis in the eastern region, western region and the central urban area were 5.31 per 100 000, 1.84 per 100 000, and 1.42 per 100 000, respectively. There were statistically significant differences among different regions (χ 2 = 1 049.17, P < 0.001). Pathogenic monitoring results revealed that 12 Brucella strains were isolated, all identified as sheep type 3. Conclusions:The incidence of brucellosis in Tangshan City is on the rise from 2007 to 2022. The incidence is mainly among middle-aged and elderly male famers, and it shows s distinct seasonal pattern. It is suggested to strengthen the prevention and control of brucellosis in the whole city.

Objective To analyze the cortical current distribution in stroke patients during anodal,cathodal and bi-hemispheric transcranial direct current stimulation(tDCS)interventions for providing a theoretical basis for the application of different modes of tDCS in the rehabilitation of stroke patients.Methods The 4 layers of head tissue structures including scalp,skull,cerebrospinal fluid and brain were reconstructed using MRI data,and assembled into a realistic head model using finite element simulation software.Then,the stroke lesion was constructed in the brain model,and the anode and cathode electrodes were constructed on the scalp model.Finally,the effective stimulation area,effective stimulation depth,and efficiency of anodal,cathodal and bi-hemispheric tDCS in the brain were simulated and analyzed.Results The results of simulation analysis showed that anodal tDCS had the strongest focusability and highest stimulation efficiency,while bipolar tDCS had the largest effective stimulation depth.In addition,the peak current densities generated by different modes of tDCS were all located at the boundary of the lesion area,and the effective stimulation areas inside the brain were also located at the lesion area.Conclusion tDCS is a promising treatment for rehabilitation following stroke.The simulation results indicate that anodal and bi-hemispheric tDCS may have superior stimulation effects than cathodal tDCS.

Objective To evaluate the performance of the detection of Mycobacterium tuberculosis(MTB)nucleic acids on the CFX Opus 96 Dx real-time fluorescence PCR(RT-PCR)analyzer to determine its clinical applicability.Methods 20 clinical sputum samples were collected,and MTB bacterial suspensions were serially diluted to prepare the samples.After extraction of nucleic acids using thermal lysis,MTB DNA was amplified by real-time fluorescent PCR(RT-PCR)using the MTB nucleic acid detection reagent on the CFX Opus 96 Dx real-time fluorescence PCR analyzer to evaluate the performance of the method,including the limit of detection(LOD),precision,cross-reactivity,anti-interference ability,personnel and inter-instrument comparison,and methodological compliance rate.Results The minimum detection limit of the CFX Opus 96 Dx real-time fluorescence PCR analyzer for detecting MTB DNA was 1×102 bacteria/ml,which aligns with the requirements of the reagent specification.The intra-batch coefficient of variation(CV)was 1.04%,1.61%and 1.29%for 3 repetitions of 5×102 bacteria/ml samples.The intra-batch CVs were 0.92%,0.74%and 0.59%for 3 repetitions of 5×103 bacteria/ml samples,which were all<5%.Common respiratory pathogens such as Staphylococcus aureus,Staphylococcus epidermidis,Pseudomonas aeruginosa,Klebsiella pneumoniae,Nocardia,Proteus mirabilis,Legionella pneumophila,Pneumocystis japonicus,Influenza A virus,Influenza B virus,Mycoplasma pneumoniae and SARS-CoV-2 do not cross-react with MTB.There was no statistically significant difference in the change in cycle threshold(Ct)values before and after the addition of the interfering substances Hemoglobin,Mucin,Rifampicin,Isoniazid,Amoxicillin and Levofloxacin to the MTB-positive specimens(all P>0.05).Comparison CVs between the two operators and all three PCR instruments were less than 5 percent.The positive compliance rate,negative compliance rate and total compliance rate of MTB DNA detected by the ABI 7500 real-time PCR analyzer and the CFXOpus 96 Dx real-time PCR analyzer were 100%.Conclusion The LoD,precision,cross-reactivity,anti-interference ability,personnel and inter-instrument comparison,and methodological compliance rate of the CFX Opus 96 Dx real-time fluorescence PCR analyzer for the detection of MTB DNA are all in line with the requirements of clinical molecular biology testing,which can provide a reliable basis for clinical testing.

Objective To investigate the mechanism of action of the Astragalus-Chinese yam combination in treating cancer-related fatigue(CRF)in mice.Methods The active components and related targets of Astragalus-Chinese yam were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform.CRF-associated targets were identified using the GeneCards database.Intersecting targets were analyzed using the DAVID database for gene ontology and kyoto encyclopedia of genes and genomes enrichment analyses.A network diagram depicting"drug-active component-intersecting targets-disease"was constructed using Cytoscape software,and a protein-protein interaction network was created to identify the top five core target proteins based on degree values.Molecular docking simulations were performed using Autodock Vina software.Twenty-five mice were divided randomly into a blank group and a modeling group in a 1∶4 ratio.After successfully establishing the CRF model using Lewis lung cancer cells,mice in the modeling group were further divided into model,Chinese yam(0.2 g/kg),Astragalus(0.6 g/kg),and Astragalus-Chinese yam combination groups(0.3+0.1 g/kg)(n=5 mice per group).The treatments were administered by gavage twice daily for 14 consecutive days.Grip-strength and forced-swimming tests were conducted.The mice were then euthanized and tissues were collected.The gastrocnemius muscles were weighed and stained with hematoxylin and eosin to reveal the muscle fiber morphology.Results A total of 23 effective active components of Astragalus-Chinese yam were identified through network pharmacology analysis,with 199 intersecting drug-disease targets.These targets mainly participated in biological processes such as protein phosphorylation through cellular components(cytoplasm,membrane,nucleus)and performed molecular functions such as protein binding.A total of 155 signaling pathways,including pathway in cancer and the phosphatidylinositol 3-kinase-protein kinase B signaling pathway,were involved in CRF.The critical targets of Astragalus-Chinese yam for CRF included serine/threonine kinase,tumor necrosis factor,epidermal growth factor receptor,B-cell lymphoma 2,and caspase 3.The active components quercetin and diosgenin interacted with the highest number of targets and demonstrated binding energies＜-5.0 kJ/mol with the five core targets,indicating strong ligand-receptor binding affinity.Mice in the Chinese yam and Astragalus groups exhibited increased grip strength and prolonged swimming times compared with the model group.Gastrocnemius muscle volume and mass were increased,with well-organized muscle fibers and clear boundaries,and the effects were even more pronounced in the Astragalus-Chinese yam combination group.Conclusions Astragalus-Chinese yam treats CRF via a multi-target,multi-pathway approach,enhancing muscle strength and endurance in mice,improving gastrocnemius muscle volume and mass,and alleviating muscle atrophy,thereby mitigating the associated symptoms of CRF in mice.