To investigate the clinical characteristics and prognosis of extracranial malignant rhabdoid tumor (eMRT) in children, and to provide a reference for the clinical treatment of this disease.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. Despite therapeutic advancements over recent decades, the prognosis for patients with metastatic CRC (mCRC) remains poor. Approximately 2%-4% of mCRC cases exhibit human epidermal growth factor receptor 2 (HER2) amplification or overexpression, defining a distinct molecular subtype. This HER2-positive status is strongly associated with primary resistance to anti-epidermal growth factor receptor (EGFR) therapies, which are the standard of care for patients with RAS wild-type tumors. Beyond its well-established role in breast and gastric cancers, HER2 has emerged as a pivotal biomarker and actionable therapeutic target in mCRC. However, selecting appropriate treatment strategies remains challenging due to patient heterogeneity and diverse molecular subtypes. This review systematically summarizes the molecular biology, diagnostic strategies, and advances in targeted therapies for HER2-positive mCRC. On the diagnostic front, we discuss the applications of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and circulating tumor DNA (ctDNA) detection technologies. We highlight discrepancies in diagnostic criteria across key clinical trials—such as HERACLES, DESTINY, and MOUNTAINEER—underscoring the urgent need for standardized, CRC-specific definitions to ensure consistent patient selection and comparability of efficacy data across studies. Although NGS enables comprehensive genomic profiling, its cost-effectiveness relative to traditional methods must be carefully considered. Therapeutically, we summarize clinical trial data for HER2-directed agents, including tyrosine kinase inhibitors (TKIs) such as tucatinib and lapatinib, monoclonal antibodies like trastuzumab, bispecific antibodies, and antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan. We review dual-targeting strategies and note recent FDA approvals that represent significant milestones in second-line treatment. Additionally, we explore the potential of combining immune checkpoint inhibitors with HER2-targeted therapies to enhance antitumor immunity through mechanisms including antibody-dependent cellular cytotoxicity (ADCC) and modulation of the tumor microenvironment. ADCs enable precise delivery of cytotoxic payloads, reducing off-target toxicity while effectively inhibiting oncogenic pathways. A substantial portion of this review is dedicated to dissecting the molecular mechanisms underlying primary and acquired resistance to HER2-targeted therapies—persistent challenges that limit clinical benefit. These mechanisms include reactivation of downstream signaling pathways such as PI3K/AKT/mTOR and MAPK, concurrent mutations in genes like KRAS or BRAF, and alterations in HER2 expression that compromise treatment efficacy. For instance, specific HER2 mutations (e.g., L755S) can reduce drug binding affinity, while ctDNA monitoring facilitates early detection of emerging resistance clones during disease progression, thereby enabling timely therapeutic adjustments. Tumor heterogeneity and dynamic interactions with the microenvironment further complicate resistance patterns observed in clinical practice. HER2-targeted therapy represents a new frontier in precision oncology for mCRC, offering renewed hope for improving patient outcomes. Realizing this potential will require continued optimization of diagnostic algorithms and treatment workflows. Future efforts must focus on overcoming resistance, validating liquid biopsy approaches for dynamic monitoring, and establishing unified clinical guidelines. HER2 has become an essential biomarker for stratifying mCRC patients beyond traditional RAS and BRAF status, underscoring the shift from empiric treatment to biomarker-driven precision medicine. International, multidisciplinary collaboration will be critical to validate emerging biomarkers and refine treatment algorithms globally.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

This paper introduces a real-world cohort research model for community-acquired pneumonia （CAP） based on the Jiangsu Traditional Chinese Medicine （TCM） Dominant Diseases Diagnosis and Treatment Data Platform. Firstly， data cleaning is performed by standardizing diagnosis， symptoms， treatment and imaging， intelligently extracting unstructured information， and cleaning and constructing a standardized database. Secondly， for cohort establishment， CAP patients across the province are screened in accordance with CAP diagnostic criteria to build a high-quality disease-specific cohort. Lastly， in terms of protocol design， the characteristics of TCM research and the CAP disease profile are considered to determine appropriate inclusion and exclusion criteria， estimate sample size， define interventions， outcomes and economic evaluations， providing a reference for real-world TCM research on CAP.

Objective To preliminary explore the imaging manifestations of digital breast tomosynthesis (DBT) and contrast-enhanced mammography (CEM) in triple-negative breast cancer (TNBC) patients with different levels of human epidermal growth factor receptor 2 (HER2) expression. Methods A retrospective analysis was conducted on TNBC patients who underwent preoperative DBT or CEM examinations at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2018 to December 2019 and Shanghai Second People’s Hospital from January 2022 to May 2025. Clinical data, pathological and immunohistochemical results, and imaging data were collected. Results A total of 69 TNBC patients pathologically confirmed as invasive ductal carcinoma were included, among which 34 underwent DBT and 35 underwent CEM. Among these patients, 34 (49.28%) had HER2-low expression and 35 (50.72%) had HER2-zero expression. DBT results showed that the proportion of spiculation signs in HER2-low group (n＝14) was significantly higher than that in HER2-zero group (n＝20; P＝0.009, P_adj＝0.045). However, there were no significant differences in breast density type, mass shape, or calcification between the two groups. CEM results showed that on low-energy images, the proportion of spiculation signs in the HER2-low group (n＝20) was higher than that in the HER2-zero group (n＝15; P＝0.011, P_adj＝0.077). Results of CEM showed that on reconstructed images, differences in background parenchymal enhancement and mass enhancement patterns between the two groups were not statistically significant; in both groups, heterogeneous enhancement was the most common, followed by homogeneous enhancement, with ring enhancement being the least common. Conclusions TNBC with low HER2 expression and TNBC with zero HER2 expression may have potential differences in the presentation of spiculation signs on DBT. However, the correlation between CEM manifestations and TNBC with different HER2 expression levels requires further research.

ObjectiveTo investigate the mechanism by which Gegen Qinliantang（GQT） improves skeletal muscle insulin resistance. MethodsThe db/m mice were used as the normal group， while db/db mice were assigned to a model group， low-dose （3.12 g·kg^-1）， medium-dose （6.24 g·kg^-1）， and high-dose （12.48 g·kg^-1） GQT groups， and a Western medicine group （semaglutide， 0.045 mg·kg^-1），n=6 in each group. All groups received corresponding interventions. Intraperitoneal glucose tolerance test （IPGTT）， intraperitoneal insulin tolerance test （IPITT）， and hematoxylin-eosin （HE） staining were used to evaluate insulin resistance and therapeutic efficacy. Serum lipid levels were measured using an automatic biochemical analyzer， and apoptosis in skeletal muscle was assessed via TUNEL assay. Transcriptome sequencing combined with gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses was performed to identify differentially expressed genes （DEGs）. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to validate gene expression. Molecular docking was applied to evaluate the binding patterns between active components of GQT and key regulatory genes to elucidate pharmacological mechanisms. ResultsCompared with the model group， the medium-dose and high-dose GQT groups showed significantly reduced fasting blood glucose （FBG） levels （P<0.01）. Triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） were markedly decreased （P<0.01）， while high-density lipoprotein cholesterol （HDL-C） was significantly increased （P<0.01）. IPGTT， IPITT， and HE staining demonstrated that GQT enhanced insulin sensitivity and restored skeletal muscle morphology. GQT also alleviated apoptosis in skeletal muscle tissue. Transcriptome analysis revealed that GQT primarily affected biological processes such as oxidative phosphorylation， metabolic pathways， cellular processes， and protein binding. Real-time PCR results showed that CBR2， CDK6， F830016B08Rik， IL-1β， Rab27b， and COLEC12 were key regulatory genes. Molecular docking demonstrated that CBR2， IL-1β， Rab27b， and COLEC12 formed stable binding with the main active components of GQT. The therapeutic effects of high- and medium-dose GQT were comparable to those of the semaglutide group. ConclusionGQT improves skeletal muscle insulin resistance， potentially by regulating apoptosis as part of its underlying biological mechanism.

The promulgation of the Technical Specifications for Clinical Use of Blood (2025 Edition) signifies that China's clinical blood transfusion management has transitioned from mere technical operations to a new stage centered on patient blood management (PBM). Through an in-depth comparison of the new and old specifications, this paper analyzes the core transformations regarding conceptual reconstruction, legal alignment, technological upgrades, and closed-loop management. The new specifications establish PBM principles, reinforce legal safeguards for informed consent and emergency treatment, and construct a comprehensive, refined quality control system by specifying compatibility testing standards and introducing a post-transfusion evaluation system. Medical institutions should seize this opportunity to update management protocols and information systems, deepen multidisciplinary collaboration, and drive the profound transformation of clinical blood use from focusing solely on safety assurance to placing equal emphasis on science and value.

Driven by the growing practical need to accelerate drug development and the continuous innovation of trial design in recent years， the number of protocol amendments during clinical trials have gradually increased， and the changed contents have become more flexible and complex， which significantly heightens the difficulty of ethical review on amendments. Against this backdrop， it is of great importance to fully leverage the role and responsibilities of ethics committees， effectively control clinical trial risks， and ensure subject safety. This paper analyzed development trends of protocol amendments in recent years， sorted out requirements for protocol amendments in Chinese regulations and guiding principles， and examined difficulties of amendment ethical review in practical work. Based on these， targeted strategies and recommendations were proposed， namely， strengthening the integration with scientific review， enhancing the formal review， adjusting the scope of review according to approval notifications， and adopting appropriate review methods， with a view to providing insights and references for the management of the amendment ethical review in drug clinical trials.

BACKGROUND:One of the advantages of clear aligner treatment is molar distalization.However,tooth tilting movement and loss of anterior anchorage may occur during treatment.There are few studies on whether these problems can be improved by selecting clear aligners with different thicknesses and edges to improve the clinical treatment effect.OBJECTIVE:To analyze the control ability of clear aligners with different thickness and edges on the central incisor,lateral incisor,and second molar when pushing the maxillary second molar distally by three-dimensional finite element analysis.METHODS:Three-dimensional finite element analysis models of bilateral maxillary second molar distalization with clear aligner,maxillary dentition,periodontal ligament,and alveolar bone with different thicknesses and margins were established by Mimics,Geomagic Wrap,3-matic and SolidWorks software,respectively.There were 16 combinations of four thicknesses(0.4,0.5,0.625,and 0.75 mm)and four margins(scallop,straight,straight extension 2 mm and straight extension 4 mm).The data were imported into Ansys Workbench software for design and solution.The mean value,peak value and distribution of the periodontal ligament equivalent stress of the second molar,the equivalent stress and the maximum initial displacement of the second molar,and the control ability of each appliance on the second molar,central incisor,and lateral incisor were analyzed.RESULTS AND CONCLUSION:(1)The mean equivalent stress of periodontal ligament of the second molar,the equivalent stress of the second molar and the maximum initial displacement of the second molar increased with the extension of the appliance edge and the increase of the thickness of the appliance in the 16 groups of models.(2)When the thickness of appliances was the same,the maximum equivalent stress of the second molar in the linear appliance group was the highest,and the maximum equivalent stress of the second molar in the linear extended appliance group was greater than that in the scallop appliance group.When the edge of the appliance was the same,the periodontal ligament equivalent stress peak of the second molar increased with the increase of the thickness of the appliance.The equivalent stress distribution in the periodontal ligament of the second molar in the linear extendable appliance group was more uniform than that in the scallop appliance group and the linear appliance group.(3)When the thickness of the appliance was the same,the scallop-shaped appliance had the worst control on the second molar.When the edge of the appliance was the same,with the increase of the thickness of the appliance,the control of the second molar by the linear extender appliance was gradually stronger than that by the linear appliance.The control of the central incisor was stronger and more stable with the linear extended 2 mm appliance,while the control of the lateral incisor was stronger and more stable with the linear appliance.(4)The results showed that when using clear aligners to push molars distally,extending the edge of the appliance could improve the control of the molars and reduce the tilting movement of the teeth.The design of a straight extension margin of 2 mm for the central incisor and a straight edge for the lateral incisor can enhance the control of the anchorage incisor and reduce the labial inclination of the anterior teeth.

BACKGROUND:The local immune microenvironment plays an important regulatory role in the process of bone formation,and the immune system is intricately linked to the skeletal system.OBJECTIVE:To systematically review the promotion of bone regeneration from three aspects:immune cell regulation of microenvironment,regulation of immune response by small extracellular vesicles,and induction of immune response by bone biomaterials,and to elucidate the immune regulatory mechanisms involved in bone regeneration.METHODS:Relevant literature was retrieved from PubMed,CNKI,WanFang Database,and VIP Database,using the search terms of"osteoimmunology,immune microenvironment,small extracellular vesicles,bone regeneration,bone tissue repair,biomaterials,and tissue engineering"in English and Chinese.Repeat and irrelevant literature was screened and removed,and 92 articles that met the criteria were selected for intensive reading and review.RESULTS AND CONCLUSION:Multiple immune cells and bone cells are in the same microenvironment,and immune cells can regulate the differentiation and activity of bone cells,collectively forming an immune microenvironment that affects bone regeneration.Neutrophils can significantly reduce local inflammatory responses in the early stages of bone injury,creating a favorable microenvironment for bone regeneration.M1 macrophages can clear foreign bodies and reduce early inflammatory responses,while M2 macrophages can promote the expression of osteogenic markers and factors,playing an important role in the repair process of bone injury.B cells and T cells can directly or indirectly affect the generation and activity of osteoblasts and osteoclasts,regulate bone metabolism,and promote bone regeneration.Extracellular vesicles of small cells regulate the local immune microenvironment through paracrine secretion,promoting bone formation and angiogenesis at the site of bone injury.The metal ions,surface hydrophilicity,porosity,pore size,surface morphology,and surface roughness on the surface of biomaterials can directly regulate local immune responses,and have anti-inflammatory,angiogenic,and osteogenic effects,thereby accelerating bone regeneration.