OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation

OBJECTIVES: To identify potential plasma lipidomic biomarkers that distinguish non-metastatic medulloblastoma (nmMB) from metastatic medulloblastoma (mMB) in children. METHODS: In this prospective study, 17 children with mMB and 20 matched children with nmMB were enrolled. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Lipid metabolites were evaluated for their associations and diagnostic performance. RESULTS: Orthogonal partial least squares discriminant analysis based on lipid profiles clearly separated nmMB from mMB, and 14 differential lipids were identified, including DG(18:2/20:4/0:0) and SM(d18:1/20:0). Receiver operating characteristic analysis showed nine metabolites with area under the curve greater than 0.7. Differential lipids were enriched in sphingolipid, glycerophospholipid, and arachidonic acid metabolism, suggesting an association with the metastatic phenotype. CONCLUSIONS Plasma lipidomics provides a new approach to identify mMB, and the identified lipid metabolites may support early diagnosis and treatment, prognostic assessment, and selection of therapeutic targets for metastatic medulloblastoma.
Humans ; Medulloblastoma/diagnosis* ; Lipidomics ; Child ; Male ; Female ; Child, Preschool ; Cerebellar Neoplasms/blood* ; Biomarkers, Tumor/blood* ; Neoplasm Metastasis ; Prospective Studies ; Adolescent ; Lipids/blood*

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

OBJECTIVE: Cancer remains a significant global health challenge, necessitating the development of effective treatment approaches. Developing synergistic therapy can provide a highly promising strategy for anti-cancer treatment through combining the benefits of various mechanisms. METHODS: In this study, we developed a synergistic strategy for chemo-photothermal therapy by constructing nanocomposites using gold nanorods (GNRs) and tetrahedral framework nucleic acids (tFNA) loaded with the anti-tumor drug doxorubicin (DOX). RESULTS: Our in vitro studies have systematically clarified the anti-cancer behaviors of tFNA-DOX@GNR nanocomposites, characterized by their enhanced cellular uptake and proficient lysosomal escape capabilities. It was found that the key role of tFNA-DOX@GNR nanocomposites in tumor ablation is primarily due to their capacity to induce cytotoxicity in tumor cells via a photothermal effect, which generates instantaneous high temperatures. This mechanism introduces various responses in tumor cells, facilitated by the thermal effect and the integrated chemotherapeutic action of DOX. These reactions include the induction of endoplasmic reticulum stress, characterized by elevated reactive oxygen species levels, the promotion of apoptotic cell death, and the suppression of tumor cell proliferation. CONCLUSION This work exhibits the potential of synergistic therapy utilizing nanocomposites for cancer treatment and offers a promising avenue for future therapeutic strategies.
Doxorubicin/chemistry* ; Gold/chemistry* ; Nanotubes/chemistry* ; Humans ; Nanocomposites/chemistry* ; Cell Line, Tumor ; Nucleic Acids/chemistry* ; Antibiotics, Antineoplastic/pharmacology* ; Antineoplastic Agents/administration & dosage*

Occlusal rehabilitation is an effective means of treating tooth wear, edentulous jaws and other oral diseases. Among them, full-mouth fixed occlusal reconstruction can effectively restore aesthetics and function, but the complexity of the clinical process, the high sensitivity of the technique, and the high incidence of various complications have always drawn much attention. With the application and development of digital technology in occlusal rehabilitation, the treatment outcome has been improved compared with traditional treatment. However, there are many kinds of digital technology with different efficacy, how to build an efficiently standardized digital clinical technical solution is a current difficulty. Therefore, combined with the long-term work of the department of prosthodontics in our hospital, in this paper, the minimum (occlusal perception of thickness) and maximum (centric relation) geometric quantities which should be paid attention to during reconstruction are put forward. We systematically organized the clinical procedure of digital full-mouth fixed occlusal rehabilitation used in our department for a long time. In conclusion, a 5-stage 19-step or n-step solution (5-19N for short) characterized by "from large to small" restorative space splitting logic is proposed. It has a certain reference value for the future use of digital technology to deal with complex occlusal rehabilitation cases.
Humans ; Dental Occlusion ; Computer-Aided Design ; Mouth, Edentulous/rehabilitation*

Objective To investigate the effect of dynamic monitoring of occlusal force on the final therapeutic effect and the change of periodontal supporting tissue during combined periodontal orthodontic treatment.Methods The periodontal clinical index of 20 patients with traditional periodontal orthodontic treatment and 20 patients with combined periodontal orthodontic treatment assisted by T-Scan Ⅲ and Anycheck digital occlusion analysis system were compared before,during and after treatment,as well as the changes of bite force,bite time and tooth mobility in the experimental group.Results The depth of periodontal pocket(PD),loss of attachment(AL),bleeding index(BI)and tooth looseness were significantly reduced after combined periodontal orthodontic treatment in both groups.In the control group,the percentage of anterior and posterior biting force changed obviously,and the occlusion force balance was improved.Conclusion The combined treatment of periodontitis and orthodontics can improve the periodontal tissue of patients with periodontitis,and T-Scan system can observe and guide the adjustment of occlusal and better achieve occlusion force balance.

Objective To construct a regulatory network of competing endogenous RNA(ceRNA)with prognostic value for bladder urothelial carcinoma(BLCA),and analyze the relationship between key messenger RNA(mRNA)and immune function.Methods The UCSC Xena database was used to download mRNA expression data from 404 BLCA patients and 28 normal individuals and key mRNAs were screened by differential analysis.ENCORI database was utilized to search microRNAs(miRNAs)that bind to key mRNAs and all long non-coding RNAs(LncRNAs)that bind to miRNAs.The expression data of miRNA and LncRNA were downloaded from TCGA database,co-expression analysis was performed to identify key mRNA with all miRNAs and miRNA with all LncRNAs,and thus key miRNAs and LncRNAs were screened out.Survival analysis was conducted based on the differences in expression levels of these key mRNAs,miRNAs,and LncRNAs between tumor patients and normal individuals,and finally a ceRNA regulatory network was constructed.The correlation between key mRNAs and immune cells,immune checkpoints(CD274,PDCD1 and CTLA4),and immune cell marker genes(IG)was analyzed using the TIMER 2.0 database.Results A total of 22 key mRNAs were screened,with the most significant difference being proline 3-hydroxylase 4(P3H4).The expression of P3H4 in patients with BLCA was high,and survival time was shorter in patients with high expression.A sum of 33 miRNAs and 14 LncRNAs were screened using the key mRNAs as the central link.Through co-expression analysis and survival analysis,hsa-miR-151a-3p and MIR100 HG were identified as the key miRNA and key LncRNA with prognostic value.The differences in the above analysis results were statistically significant(all P＜0.05).Based on these findings,a ceRNA regulatory network consisting of 1 mRNA,1 miRNA,and 1 LncRNA was constructed.Immunoassay firstly revealed a significant positive correlation between double positive T cells and P3H4 expression in the tumor microenvironment of BLCA.Moreover,there were 3 types of immune cells(tumor-associated neutrophils,and tumor-associated macrophages,dendritic cells),3 immune checkpoints(CD274,PDCD1,CTLA4),and 15 IGs with significant correlation with P3H4.These differences were statistically significant(all P＜0.01).Conclusion This study could help to reveal the progression mechanism of BLCA.The constructed ceRNA network and immune analysis can offer new insights into potential biological targets and immunotherapy directions for the diagnosis,treatment,and prediction of BLCA patients.

[Objective]To investigate the effect of remnant cholesterol(RC)/high-density lipoprotein cholesterol(HDL-C)ratio on coronary computed tomography-derived fractional flow reserve(FFRct)in coronary heart disease(CHD)patients with critical lesions.[Methods]A retrospective study was done on patients who were admitted to our de-partment and underwent coronary computed tomography angiography(CCTA)from January 1,2022 to December 31,2022.All the 304 culprit vessels from the 219 patients with moderate coronary artery stenosis(50%～70%)were divided in-to FFRct ischemia group(FFRct≤0.8,N=108)and FFRct non-ischemia group(FFRct>0.8,N=111).Multivariate logis-tic regression analysis was used to explore the influencing factors of FFRct≤0.8 in CHD patients with critical lesions.Re-ceiver operating characteristic(ROC)curve was drawn to evaluate the predictive value of RC/HDL-C for FFRct≤0.8.Pear-son correlation analysis was used to assess whether there was a correlation between RC/HDL-C and FFRct.[Results]There were significantly more diabetic patients in FFRct ischemia group(P<0.001).RC/HDL-C ratio,levels of RC,non-HDL-C,APOB,HbA1c and FPG in FFRct ischemic group were significantly increased(P<0.05).Pearson correlation analysis showed that the RC/HDL-C ratio,levels of RC,Non-HDL-C,TC,TG,LDL-C,HDL-C,LP(a),HbA1c,and FPG were all significantly negatively correlated with FFRct values(P<0.05).Univariate logistic regression analysis showed that diabetes mellitus,RC/HDL-C ratio,levels of RC,non-HDL-C,TG,LP(a),HbA1c and FPG were significantly correlated with FFRct≤0.8(P<0.05).Multivariate logistic regression analysis showed that RC/HDL-C ratio was a predictor of FFRct≤0.80(OR=4.682,95%CI 1.197～18.316,P<0.05).[Conclusions]RC/HDL-C ratio is independently correlated with FFRct≤0.8 in CHD patients with moderate stenosis and it is a potential indicator for evaluating coronary functional ischemia.

Objective To propose an algorithm to extract fetal ECG signals from mixed signals of maternal abdominal wall with high signal-to-noise ratio and clear waveforms by combining kernel principal component analysis(KPCA),fast independent component analysis(FastICA)and singular value decomposition(SVD).Methods Firstly,KPCA was used to downscale the maternal ECG signals,and then the improved negative entropy-based FastICA was applied to processing the downscaled data to obtain the independent components.Subsequently,sample entropy was introduced for signal channel selection,and the signal channel containing the most maternal information was selected.SVD was performed on the selected maternal channel to get an approximate estimate of the maternal ECG signals,which was then subtracted from the abdominal wall source signals to obtain a preliminary estimate of the fetal ECGs.Finally,the pure fetal ECG signals were successfully separated using a modified negentropy-based FastICA.The proposed algorithm was validated in the Abdominal and Direct Fetal Electrocardiogram Database(ADFECGDB)and the PhysioNet 2013 Challenge database.Results The proposed algorithm gained advantages in both subjective visualization and objective evaluation metrics,which had the sensitivity,positive predictive value and F1 value of fetal QRS compound wave respectively being 99.74％,98.85％and 99.30％for the ADFECGDB database,and 99.10％,97.87％and 98.48％for the PhysioNet 2013 Challenge database.Conclusion The fetal ECG signal extraction algorithm incorporating KPCA,FastICA and SVD effectively handles the additional noise while extracting fetal ECG signals,which provides strong support for the early diagnosis of fetal diseases.[Chinese Medical Equipment Journal,2024,45(7):1-7]

Objective To plan microwave antenna puncture direction effectively and realize personalized preoperative simulation by exploring microwave ablation(MWV)outcomes of lung cancer based on real anatomical model.Methods Firstly,a personalized MWA simulation model consisting of the lung tissue,tumor and vascular system was constructed based on the lung CT data of real patients.Secondly,the MWA effect was simulated by coupling 2 physical fields including an electromagnetic field and a biological heat transfer field,so as to determine the volume of the ablation thermocoagulation zone and the temperature distribution of the lung tissue.Finally,the effects of the vascularized network on the ablation results were quantitatively evaluated in terms of conductivity and blood perfusion,and the ablation results were analyzed with different distances between the large vessels and the antennae(5 and 10 mm from the antennae tips)and puncture angles(large vessels parallelling or intersecting with the antennae tips).Results The vascularized network reduced the volume of the thermocoagulation zone by 0.5％to 3.7％,and blood perfusion made the ablation temperature and the volume of the thermocoagulation zone decreased significantly.The cooling effect gradually diminished with the increase of the distance between the large vessels and the antenna.With the same treatment parameters,the thermocoagulation zone formed when the large vessels paralleled with the antenna was obviously larger than that when the vessles intersected with the antenna.Conclusion Personalized MWA simulation analysis based on real CT data contributes to clarifying the temperature distribution and damage estimation close to the actual situation,which provides guidance and reference for precise treatment of the lung tumor and determination of microwave antenna puncture direction.[Chinese Medical Equipment Journal,2024,45(9):27-34]