Traditional Chinese medicine(TCM) capable of clearing heat and removing toxin is most commonly used in clinical practice and has the effect of removing fire-heat and toxin. Studies have shown that most of the Ilex plants have the effect of clearing heat and removing toxin, among which the varieties of I. cornuta, I. pubescens, I. rotunda, I. latifolia, and I. chinensis are most widely used. These plants generally contain triterpenoids and their glycosides, alkaloids, flavonoids, phenylpropanoids, and other chemical components, especially pentacyclic triterpenoids. According to their skeletons, pentacyclic triterpenoids can be divided into the oleanane type, the ursane type, the lupinane type, etc. Among them, ursane-type components are the most abundant, and 136 species have been found so far. These components have been proved to have pharmacological effects such as anti-inflammatory, anti-tumor, hypolipidemic, anti-thrombosis, cardiomyocyte-protective, antibacterial, and hepatoprotective effects. Therefore, this paper systematically reviews the domestic and foreign literature on Ilex plants with a focus on the research progress on pentacyclic triterpenoids and their pharmacological activities, aiming to provide reference for the development of TCM resources with the effect of clearing heat and removing toxin.
Ilex/chemistry* ; Plants, Medicinal/chemistry* ; Pentacyclic Triterpenes/pharmacology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Animals

[This corrects the article DOI: 10.1016/j.apsb.2022.03.002.].

Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Objective:To investigate the influencing factors of adverse reactions of reconstructive flaps after postoperative precision radiation therapy for head and neck tumors.Methods:Medical records of 46 patients who underwent radiotherapy after flap reconstruction for head and neck tumors in the Affiliated Hospital of Inner Mongolia Medical University between January 2016 and October 2022 were retrospectively analyzed. The overall survival (OS), local regional control (LRC) and dosimetric parameters after radiotherapy were analyzed. The adverse reactions mainly including radiation dermatitis and flap necrosis at 3 and 6 months after radiotherapy, flap atrophy, flap fibrosis, dysphagia and chewing dysfunction at 12 and 24 months after radiotherapy were recorded. Adverse reactions were graded using the common terminology criteria for adverse events (CTCAE) version 5.0. Quantitative data were analyzed by one-way analysis of variance or rank-sum test. Qualitative data were analyzed by chi-square test or Fisher's exact test. Multivariate analysis of influencing factors of adverse reactions was performed using binary logistic stepwise regression.Results:All 46 patients were aged 57.6 years on average. The median follow-up time was 65 months (12-100 months). After the follow-up, 22 patients died, 6 recurred, and 7 had distant metastases. The 5-year OS rate was 48% and 5-year LRC rate was 69%. The incidence of radiation dermatitis was decreased over time after the end of radiotherapy: 80% (37/46) and 65% (30/46) at 3 months and 6 months after radiotherapy, respectively. The incidence of grade 3 radiation dermatitis was 11% (5/46) and 0 at 3 and 6 months after radiotherapy, respectively. The incidence of grade 2 flap necrosis was 4% (2/46) at 3 months after radiotherapy. At 12 months after radiotherapy, the incidence of flap atrophy and fibrosis was 83% (38/46) and 67% (31/46) , and the incidence of grade 3 flap atrophy and fibrosis was equally 4% (2/46) , respectively. All patients had dysphagia and chewing dysfunction at 12 months after radiotherapy. At 24 months after radiotherapy, 83% (38/46) and 61% (28/46) of patients still had dysphagia and chewing dysfunction. Multivariate regression analysis showed that irradiated flap volume, total radiotherapy dose, pharyngeal constrictor D mean and pharyngeal constrictor V 60 Gy, the interval between surgery and radiotherapy, gender and age were the independent influencing factors of adverse reactions of reconstructive flaps after precision radiation therapy for head and neck tumors. Conclusions:For patients undergoing flap reconstruction for head and neck tumors, under the premise of ensuring tumor control, the dose to normal tissue and flap blood supply area should be strictly limited, the irradiated volume should be reduced, and the interval between surgery and radiotherapy should be shortened (≤6 weeks) to reduce the risk of adverse reactions. Hypo-fractionated radiotherapy plan should be formulated or the total radiotherapy dose should be appropriately adjusted for elderly patients to reduce long-term complications.

Objective·To investigate the genetic etiology of a rare and complex case clinically suspected to be methylmalonic acidemia(MMA),but with negative whole exome sequencing(WES)results,using a multi-omics sequencing approach.Methods·DNA and RNA samples were extracted from the peripheral blood of the proband and both parents.Targeted MMA-related gene Panel sequencing and WES were first performed.Subsequently,RNA sequencing(RNA-seq)and whole genome sequencing(WGS)were conducted to comprehensively analyze the child's genetic variants,their origins and potential inheritance patterns.Results·No pathogenic variants associated with the patient's phenotype were identified through the MMA Panel or standard WES analysis.Extended analysis of WES suggested the possibility of uniparental disomy(UPD)of chromosome 4.WGS revealed a homozygous splice-site variant(c.-66+2T>C)in the non-coding region of the metabolism of cobalamin associated A(MMAA)gene.The variant was located in the 5'untranslated region(5'UTR),specifically at the second base downstream of the splice donor site of exon 1(reference sequence:NM_172250).In genomic coordinates(hg19),the variant was located at base 146540561 on chromosome 4(chr4:146540561).Sanger sequencing confirmed that the mother was heterozygous for this variant,while the father did not carry it.RNA-seq showed no detectable expression of the MMAA gene on chromosome 4 in the patient.This was further confirmed by reverse transcription real time quantitative PCR,indicating nearly absent mRNA expression,suggesting that the non-coding splice-site variant affected transcriptional expression.Conclusion·A homozygous splice-site variant(c.-66+2T>C)in the non-coding region of the MMAA gene—outside the coverage of WES—is likely the pathogenic cause in this case,presumably resulting from maternal UPD of chromosome 4.

BACKGROUND:Observational studies have found a dual effect of lipids and immune cells on osteoarthritis progression,but the exact mechanism of action is not yet clear.OBJECTIVE:To investigate whether the causal relationship between lipids and knee osteoarthritis is regulated by immune cells.METHODS:179 lipids were obtained from the Linda Ottensman database,731 immune cell-associated single nucleotide polymorphisms were obtained from Open GWAS as instrumental variables,and genome-wide association data for knee osteoarthritis were obtained from the Osteoarthritis Genetics Consortium.First,we used a two-sample Mendelian randomization method to investigate the causal relationships between lipids and knee osteoarthritis,between immune cells and knee osteoarthritis,and between lipids and immune cells from a genetic perspective.In addition,Bayesian-weighted Mendelian randomization verified the causal relationship between lipids and knee osteoarthritis,and reverse Mendelian randomization and Steiger directionality test assessed the positive relationship.Second,sensitivity analyses were performed,including Cochran's Q test to eliminate heterogeneity,MR-PRESSO global test and MR-Egger intercept to rule out horizontal pleiotropy,and leave-one-out method to assess the effect of individual single nucleotide polymorphism drivers on random estimates.Finally,the mediating effect of specific immune cell traits in the causal relationship between lipids and knee osteoarthritis was determined by a two-step Mendelian randomization method.RESULTS AND CONCLUSION:The inverse variance weighting method and Bayesian-weighted algorithm together identified eight lipid species that were causally associated with knee osteoarthritis.The results of Cochran's Q,MR-PRESSO,and MR-Egger intercept were not statistically significant(P<0.05).Meanwhile,a total of three sets of mediated relationships were calculated,with the lowest mediation percentage of 11.85%and the highest of 45.48%.These findings indicate the level of immune cells plays a potential role in the regulatory process of lipids and knee osteoarthritis,which provides new perspectives for in-depth exploration of knee osteoarthritis.

Objective To construct a dynamic framework for bidirectional transitions of mild cognitive impairment(MCI),quantifying both rare reversion and high-risk progression trajectories in cognitive dynamics.Methods Patients diagnosed with MCI at baseline from 2005 to 2022 and completed at least two follow-up visits were selected from the Alzheimer's Disease Neuroimaging Initiative(ADNI),and a retrospective cohort was constructed.Demographic information,APOEε4 genotype,and neuropsychological scales data were collected.Longitudinal cognitive assessments were functionally reconstructed using multivariate functional principal component analysis(MFPCA),with functional principal components(FPCs)extracted based on cumulative variance contribution rate(PVE＞90％).Functional multi-state Markov models were developed to estimate inter-state transition intensities,year to year transition probabilities,and covariate effects.Results Among 1,019 MCI patients(4,657 follow-up visits),93(9.1％)reverted to normal cognition,while 359(35.2％)progressed to Alzheimer's disease(AD).Longitudinal trajectory analysis revealed significant heterogeneity:progressive MCI＞stable MCI＞reverted MCI in the first functional principal component(MFPC1)scores.The transition intensity for MCI reversion(0.020)was approximately one-fourth of the AD progression risk(0.086),but the post-reversion cognitive re-impairment intensity was 0.138.Reduced MFPC1(HR=0.993,95％Cl:0.991,0.995)and elevated MFPC2(HR=1.004,95％Cl:1.001,1.007)were closely associated with MCI reversion.Conclusion MCI exhibits marked heterogeneity in longitudinal cognitive trajectories.Although reversion is rare,reversed patients remain at high risk of cognitive re-impairment.

Relevant China's literature on the application of brain-computer interface technology in the field of rehabilita-tion of stroke patients was retrieved in the China Knowledge Network database from its establishment to December 31,2024,and CiteSpace visual analysis software was used to analyze the selected literature in terms of trend of annual publica-tion number,author collaboration network,keyword co-occurrences and emergences and to generate a corresponding knowledge map.It's pointed out brain-computer interface technology showed significant application potential for motor function recovery and neurorehabilitation,which had the research hotspots of the cross technologies covering motor imagina-tion,rehabilitation training and virtual reality and the research frontiers of the fusion application of intelligent algorithms of deep learning and pattern recognition.The challenges and future development directions of the field were investigated,and references were provided for promoting the application of brain-computer interface technology to rehabilitation of sroke patients in China.[Chinese Medical Equipment Journal,2025,46(9):65-69]

Objective:To explore the construction of an evaluation model for aortic root anatomy and calcium burden in patients with bicuspid aortic valve (BAV) stenosis before transcatheter aortic valve replacement (TAVR) based on deep learning (DL) algorithms.Methods:A retrospective collection of 362 BAV stenosis patients who underwent TAVR from September 2023 to May 2024 was performed. All patients underwent cardiac CT angiography. The patients were divided into training group ( n=104), internal validation group ( n=206), and external validation group ( n=52). A DL model was trained on the training dataset to assess aortic root anatomy and calcification burden. The evaluation included the segmentation accuracy of the algorithm, the measurement performance of key anatomical structures (i.e., valve leaflets and type-1 and type-2 fusion raphe), and calcification burden, as well as the measurement efficiency. Overall segmentation performance was assessed using the average Dice coefficient (ADC). The fine-scale segmentation quality was validated by the 95th-percentile Hausdorff distance (HD-95) and the average symmetric surface distance (ASSD). The consistency of the measurement results was assessed using the Pearson correlation coefficient and the intraclass correlation coefficient ( ICC) with a two-way mixed model for absolute agreement. In addition, the total time and total mouse movement distance required for manual assessment versus the DL model on the validation datasets were recorded and compared. Results:The algorithm demonstrated excellent segmentation performance on aortic root anatomical targets, achieving outstanding consistency within both internal and external validation datasets (0.955

Neuraminidase(NA),a glycoprotein on the surface of the influenza virus,plays a crucial role in viral escape and serves as a stable target for drug candidates.Monoclonal antibodies targeting the NA active site can bind to multiple influenza virus subtypes and inhibit the spread of influenza virus through various mechanisms,such as neutralizing,mediating antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotox-icity.In vivo experiments have shown that human monoclonal antibodies targeting the influenza virus NA can ef-fectively exert preventive and therapeutic effects,rescuing mice infected with lethal doses and reducing viral ti-ters in lungs of mice.This article provides a review of the currently reported human monoclonal antibodies targe-ting NA of Influenza A and Influenza B viruses,providing new ideas and prospects for the subsequent development of anti-influenza drugs.