Objective:To analyze the clinical characteristics of children with head and neck rhabdomyosarcoma (RMS) and to summarize the mid-long term efficacy of Beijing Children′s Hospital Rhabdomyosarcoma 2006 (BCH-RMS-2006) regimen and China Children′s Cancer Group Rhabdomyosarcoma 2016 (CCCG-RMS-2016) regimen.Methods:A retrospective cohort study. Clinical data of 137 children with newly diagnosed head and neck RMS at Beijing Children′s Hospital, Capital Medical University from March 2013 to December 2021 were collected. Clinical characteristic of patients at disease onset and the therapeutic effects of patients treated with the BCH-RMS-2006 and CCCG-RMS-2016 regimens were compared. The treatments and outcomes of patients with recurrence were also summarized. Survival analysis was performed by Kaplan-Meier method, and Log-Rank test was used for comparison of survival rates between groups.Results:Among 137 patients, there were 80 males (58.4%) and 57 females (41.6%), the age of disease onset was 59 (34, 97) months. The primary site in the orbital, non-orbital non-parameningeal, and parameningeal area were 10 (7.3%), 47 (34.3%), and 80 (58.4%), respectively. Of all patients, 32 cases (23.4%) were treated with the BCH-RMS-2006 regimen and 105 (76.6%) cases were treated with the CCCG-RMS-2016 regimen. The follow-up time for the whole patients was 46 (20, 72) months, and the 5-year progression free survival (PFS) and overall survival (OS) rates for the whole children were (60.4±4.4)% and (69.3±4.0)%, respectively. The 5-year OS rate was higher in the CCCG-RMS-2016 group than in BCH-RMS-2006 group ((73.0±4.5)% vs. (56.6±4.4)%, χ2=4.57, P=0.029). For the parameningeal group, the 5-year OS rate was higher in the CCCG-RMS-2016 group (61 cases) than in BCH-RMS-2006 group (19 cases) ((57.3±7.6)% vs. (32.7±11.8)%, χ2=4.64, P=0.031). For the group with meningeal invasion risk factors, the 5-year OS rate was higher in the CCCG-RMS-2016 group (54 cases) than in BCH-RMS-2006 group (15 cases) ((57.7±7.7)% vs. (30.0±12.3)%, χ2=4.76, P=0.029). Among the 10 cases of orbital RMS, there was no recurrence. In the non-orbital non-parameningeal RMS group (47 cases), there were 13 (27.6%) recurrences, after re-treatment, 7 cases survived. In the parameningeal RMS group (80 cases), there were 40 (50.0%) recurrences, with only 7 cases surviving after re-treatment. Conclusions:The overall prognosis for patients with orbital and non-orbital non-parameningeal RMS is good. However, children with parameningeal RMS have a high recurrence rate, and the effectiveness of re-treatment after recurrence is poor. Compared with the BCH-RMS-2006 regimen, the CCCG-RMS-2016 regimen can improve the treatment efficacy of RMS in the meningeal region.

BACKGROUND:Black phosphorus has a high degree of homology with human bone,so it has been extensively studied in the field of bone tissue engineering in recent years.Since 2014,two-dimensional black phosphorus materials have garned significant attention in the field of biomedicine due to their excellent exceptional physical,chemical,and biological properties. OBJECTIVE:To summarize the advancements made in black phosphorus-based nanomaterials for bone tissue engineering,focus on the synthesis methods,osteogenic characteristics,and applications in biomaterials pertaining to two-dimensional black phosphorus nanomaterials. METHODS:Chinese and English key words were"black phosphorus,bone tissue engineering,bone defect,bone regeneration,osteogenesis."Relevant articles in PubMed and CNKI databases from January 2014 to December 2023 were searched.After exclusion and screening,96 articles were analyzed. RESULTS AND CONCLUSION:Black phosphorus nanomaterials play an important role in bone tissue engineering due to their good biocompatibility,biodegradability,photothermal action,antibacterial ability,drug loading performance,and special osteogenic effect,and are ideal candidate materials for promoting bone regeneration.The preparation of black phosphorus nanomaterials is mainly a top-down top-layer stripping method.The main principle is to weaken the van der Waals force between the black phosphorus layers by physical or chemical means to obtain a single or less layer of phosphanse,that is,black phosphorus nanosheets or quantum dots.Black phosphate-based nanocomposites are mainly divided into hydrogels,3D printing scaffolds,composite scaffolds,electrospinning,bionic periosteum,microspheres,and bionic coatings.The research of nano-black phosphorus in bone tissue engineering is in its infancy,and still faces many challenges:the behavior of black phosphorus in vivo and the interaction mechanism with various biomolecules need to be further studied.The long-term potential toxicity of black phosphorus is unknown.The manufacturing process for black phosphorus is difficult to control.Therefore,how to develop uniform size,safe,reliable,and efficient nano black phosphorus and transform it into clinical application requires interdisciplinary research on modern biomedical technology,physicochemical technology,and precision manufacturing technology.

The general models for intermediates quality analysis in the production process of Yaobitong capsule were established by near infrared spectroscopy (NIRS) combined with chemometrics, realizing the rapid determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, ginsenoside Rd and moisture. The spray-dried fine powder and total mixed granule were selected as research objects. The contents of five saponins were determined by high performance liquid chromatography and the moisture content was determined by drying method. The measured contents were used as reference values. Meanwhile, NIR spectra were collected. After removing abnormal samples by Monte Carlo cross validation (MCCV), Monte Carlo uninformative variables elimination (MC-UVE) and competitive adaptive reweighted sampling (CARS) were used to select feature variables respectively. Based on the feature variables, quantitative models were established by partial least squares regression (PLSR), extreme learning machine (ELM) and ant lion optimization least squares support vector machine (ALO-LSSVM). The results showed that CARS-ALO-LSSVM model had the optimum effect. The correlation coefficients of the six index components were greater than 0.93, and the relative standard errors were controlled within 6%. ALO-LSSVM was more suitable for a large number of samples with rich information, and the prediction effect and stability of the model were significantly improved. The general models with good predicting effect can be used for the rapid quality determination of Yaobitong capsule intermediates.

Cell models can simulate a variety of life states and disease developments, including single cells, two-dimensional (2D) cell cultures, three-dimensional (3D) multicellular spheroids, and organoids. They are essential tools for addressing complex biochemical questions. With continuous advancements in biological and cellular analysis technologies, in vitro cellular models designed to answer scientific questions have evolved rapidly. Early in vitro models primarily relied on 2D systems, which failed to accurately replicate the complex cellular compositions and microenvironmental interactions observed in vivo, let alone support sophisticated investigations into cellular biological functions. Subsequent improvements in cell culture techniques led to the development of 3D culture-based models, such as cellular spheroids. The advent of pluripotent stem cell technology further advanced the development of organoid systems, which closely mimic human organ development. Compared to traditional 2D models, both 3D cellular models and organoids offer significant advantages, including personalization and enhanced physiological relevance, making them particularly suitable for exploring molecular mechanisms of disease progression, discovering novel cellular and biomolecular functions, and conducting related studies. The imaging analysis of common cellular models primarily employs labeling-based methods for in situ imaging of targeted genes, proteins, and small-molecule metabolites, enabling further research on cell types, states, metabolism, and drug efficacy. However, these approaches have drawbacks such as poor labeling specificity and complex experimental procedures. By using cells as experimental models, mass spectrometry technology combined with morphological analysis can reveal quantitative changes and spatial distributions of various biological substances at the spatiotemporal level, including metabolites, proteins, lipids, peptides, drugs, environmental pollutants, and metals. This allows for the investigation of cell-cell interactions, tumor microenvironments, and cellular bioinformational heterogeneity. The application of these cutting-edge imaging technologies generates vast amounts of cellular data, necessitating the development of rapid, efficient, and highly accurate image data algorithms for precise segmentation and identification of single cells, multi-organelle structures, rare cell subpopulations, and complex cellular morphologies. A critical focus lies in creating deep learning models and algorithms that enhance the accuracy of cellular visualization. At the same time, establishing more robust data integration tools is essential not only for analyzing and interpreting outputs but also for effectively uncovering the biological significance of spatially resolved mass spectrometry data. Developing a cell imaging platform with high versatility, operational stability, and specificity to enable data interoperability will significantly enhance its utility in clinical research, thereby advancing investigations into disease molecular mechanisms and supporting precision diagnostics and therapeutics. In contrast to genomic, transcriptomic, and proteomic information, the metabolome can rapidly respond to external stimuli and cellular physiological changes within a short timeframe. This rapid and precise reflection of ongoing cellular state alterations has positioned spatial metabolomics as a pivotal approach for exploring the molecular mechanisms underlying physiological and pathological processes in cells, tissues, and organisms. In this review, we summarize research on cell imaging based on mass spectrometry technologies, including the selection and preparation of cell models, morphological analysis of cell models, spatial omics techniques based on mass spectrometry, mass cytometry, and their applications. We also discuss the current challenges and propose future directions for development in this field.

Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.

ObjectiveJunctophilin-2 (JPH2) is an essential structural protein that maintains junctional membrane complexes (JMCs) in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum, thereby facilitating excitation-contraction (E-C) coupling. Mutations in JPH2 have been associated with hypertrophic cardiomyopathy (HCM), but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus (MORN) repeat motifs remain incompletely understood. This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis. MethodsA recombinant N-terminal fragment of mouse JPH2 (residues1-440), encompassing the MORN repeats and an adjacent helical region, was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain. Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features. Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells. In addition, site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations, including R347C, was used to evaluate their effects on membrane interaction and subcellular localization. ResultsThe crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6 Å, revealing a compact, elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration, forming a continuous hydrophobic core stabilized by alternating aromatic residues. A C-terminal α-helix further reinforced structural integrity. Conservation analysis identified the inner groove of the MORN array as a highly conserved surface, suggesting its role as a protein-binding interface. A flexible linker segment enriched in positively charged residues, located adjacent to the MORN motifs, was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes. Functional assays demonstrated that mutation of these basic residues impaired membrane association, while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays, despite preserving the overall MORN-Helix fold in structural modeling. ConclusionThis study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2, highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions. The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis. These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.

OBJECTIVE To investigate the effects and mechanism of polysaccharides from Hedyotis diffusa （HDP） on isoniazid （INH）-induced liver injury. METHODS Healthy transgenic zebrafish with liver-specific fluorescence were divided into normal group， model group （4 mmol/L INH）， HDP low-concentration group （4 mmol/L INH+50 mg/mL HDP） and HDP high- concentration group （4 mmol/L INH+100 mg/mL HDP）. After grouping treating， the liver fluorescence area， fluorescence intensity and pathological changes of liver tissue were observed. Human liver L02 cells were divided into normal group， model group （4 mmol/L INH）， HDP low-concentration group （4 mmol/L INH+2 mg/mL HDP）， and HDP high-concentration group （4 mmol/L INH + 4 mg/mL HDP）. After grouping treating， the cell viability was detected， and the levels of alanine transaminase （ALT）， aspartate transaminase （AST）， and the content of glutathione （GSH） as well as the expression levels of silent information regulator 1 （Sirt1）， nuclear factor-erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1） and quinone oxidoreductase 1 （NQO1） proteins were detected. RESULTS Compared with the model group， the HDP low- and high-concentration groups showed varying degrees of increase in the fluorescence area and fluorescence intensity （except for HDP low-concentration group） of zebrafish liver （P＜0.05 or P＜0.01）， and the characteristics of liver injury and necrosis had been improved to varying degrees. Compared with model group， the survival rate of L02 cells， the content of GSH （except for HDP low-concentration group）， the protein expression levels of Sirt1 （except for HDP low-concentration group）， Nrf2， NQO1， HO-1 （except for HDP low-concentration group） were significantly increased in HDP low- and high-concentration groups （P＜0.05 or P＜0.01）， and the levels of ALT and AST （except for HDP low-concentration group） were significantly decreased （P＜0.05）； the number of survival cells significantly increased， while the number of damaged or dead cells significantly decreased. CONCLUSIONS HDP has a potential protective effect against INH-induced liver injury， the mechanism of which may be associated with activating Sirt1/Nrf2 signaling pathway， improving mitochondrial function and enhancing antioxidant capacity.

Objective To evaluate the value of high-throughput sequencing(HTS)data reanalysis that does not include ERBB2 copy number variation(CNV)analysis,in identifying ERBB2 amplification in patients with colorectal cancer.Methods The HTS data of 252 cases of colorectal cancer diagnosed by pathological biopsy who received peripheral blood cfDNA HTS detection samples were retrospectively analyzed.According to the HTS data of ERBB2 non-amplified samples judged by immunohistochemistry(IHC)and/or fluorescence in situ hybridization(FISH),the number of chromosome 17(Chr17)reads in the total number of reads was calculated the range of the ratio was initially determined as the threshold for prompting ERBB2 amplification.Suspected positive samples were screened according to thresholds and verified by digital PCR,IHC and FISH.Results The proportion of the number of Chr17 reads accounts for the number of total reads in the 89 cases of ERBB2 non-amplified samples determined by IHC and/or FISH ranged from 0.188 to 0.299(0.239±0.192).Using 0.298(1.25 times the mean)as the threshold indicating ERBB2 amplification,the data of 163 samples were analyzed,of which 7 cases were suspected to be positive,and the ratio ranged from 0.302 to 0.853.Among them,5 cases were determined to be positive by IHC and/or FISH,and 6 cases were confirmed to be positive by digital PCR.The ratio of the number of Chr17 reads to the number of total reads was positively correlated with the ratio of ERBB2/EIF2C1,and the correlation was good(r2=0.909).Conclusion The high-throughput sequencing data that does not cover the ERBB2 CNV analysis has a certain hint value for ERBB2 amplification in patients with colorectal cancer.

BACKGROUND:For non-traumatic osteonecrosis of the femoral head,if the femoral head collapses,it will have a great impact on the normal life of the patients.Thus,it is necessary to use an appropriate way to evaluate the risk of femoral head collapse and then to take targeted measures to delay the process of femoral head collapse. OBJECTIVE:To analyze the natural course of early osteonecrosis of the femoral head(without collapse)under different locations of necrotic lesions. METHODS:121 patients(191 hips)with early non-traumatic osteonecrosis of the femoral head who were treated in the Outpatient Department of Honghui Hospital Affiliated to Xi'an Jiaotong University from October 2016 to October 2017 were enrolled in this study.The clinical data of all patients were followed up for 5 years to observe the collapse of osteonecrosis of the femoral head and the risk coefficient of femoral head collapse among different JIC types.The collapse rate of osteonecrosis of the femoral head was calculated during the follow-up. RESULTS AND CONCLUSION:(1)A total of 191 hips were included in this study.The femoral head collapsed in 86 hips during follow-up,with a total collapse rate of 45.0%.Among the influencing factors,age,ARCO stage and JIC classification were the main influencing factors of femoral head collapse(P<0.05),but body mass index,sex,incidence side and pathogenic factors were not the main influencing factors(P>0.05).(2)Among 191 hips,in JIC classification,the total collapse rates of type A,type B,type C1 and type C2 were 11.1%(2/18),30.2%(16/53),52.4%(43/82),and 65.8%(25/38),respectively.There were significant differences in the total collapse rate of the femoral head among all types(P<0.05).The collapse risk results showed that the collapse risk of type B,type C1 and type C2 was 2.41,5.22 and 7.89 times higher than that of type A,respectively.(3)Both JIC classification and ARCO stage were correlated with femoral head collapse(P<0.01).There was no significant difference in the collapse rate of the femoral head among all JIC types in ARCO I stage hips(P>0.05).In the hips with ARCO II stage,the collapse rates of the femoral head of JIC types A,B,C1 and C2 were 1.2%,19.5%,50.0%and 29.3%,respectively,and there were significant differences in the collapse rates among different types(P<0.05).(4)During follow-up,the collapse rates of the femoral head in the first to fifth years were 29.3%,7.9%,4.7%,2.6%and 0.5%,respectively.(5)Results showed that for early non-traumatic osteonecrosis of the femoral head,the risk of collapse of osteonecrosis of the femoral head is high within one year,and the location of the focus of osteonecrosis affects the risk of collapse of the femoral head.The effect of the location of the focus on the prognosis of the disease should be considered in clinical treatment.

Aural vertigo frequently encountered in the otolaryngology department of traditional Chinese medicine （TCM） mainly involves peripheral vestibular diseases of Western medicine， such as Meniere's disease， benign paroxysmal positional vertigo， vestibular neuritis， and vestibular migraine， being a hot research topic in both TCM and Western medicine. Western medical therapies alone have unsatisfactory effects on recurrent aural vertigo， aural vertigo affecting the quality of life， aural vertigo not relieved after surgery， aural vertigo with complex causes， and children's aural vertigo. The literature records and clinical practice have proven that TCM demonstrates unique advantages in the treatment of aural vertigo. The China Association of Chinese medicine sponsored the "17th youth salon on the diseases responding specifically to TCM： Aural vertigo" and invited vertigo experts of TCM and Western medicine to discuss the difficulties and advantages of TCM diagnosis and treatment of aural vertigo. The experts deeply discussed the achievements and contributions of TCM and Western medicine in the diagnosis and treatment of aural vertigo， the control and mitigation of the symptoms， and the solutions to disease recurrence. The discussion clarified the positioning and advantages of TCM treatment and provided guidance for clinical and basic research on aural vertigo.