1.HER2 in Metastatic Colorectal Cancer: Diagnostic and Therapeutic Opportunities and Challenges
Zhao-Tao PAN ; Feng-Yu GAI ; Chen CHEN ; Tong LI ; Yan-Ping QING
Progress in Biochemistry and Biophysics 2026;53(4):936-950
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.
2.Collection, storage and utilization of lung transplant tissue samples
Yixing LI ; Xue SHI ; Hongyi WANG ; Runyi TAO ; Ye SUN ; Ailing SU ; Liyan TONG ; Jinteng FENG ; Yanpeng ZHANG ; Shuo LI ; Yawen WANG ; Guangjian ZHANG
Organ Transplantation 2025;16(1):147-155
After continuous development and improvement, lung transplantation has become the preferred means to treat a variety of benign end-stage lung diseases. However, the field of lung transplantation still faces many challenges, including shortage of donor resources, preservation and maintenance of donor lungs, and postoperative complications. Lung tissue samples removed after lung transplantation are excellent clinical resources for the study of benign end-stage lung disease and perioperative complications of lung transplantation. However, at present, the collection, storage and utilization of tissue samples after lung transplantation are limited to a single study, and unified technical specifications have not been formed. Based on the construction plan of the biobank for lung transplantation in the First Affiliated Hospital of Xi'an Jiaotong University, this study reviewed the practical experience in the collection, storage and utilization of lung transplant tissue samples in the aspects of ethical review, staffing, collection process, storage method, quality control and efficient utilization, in order to provide references for lung transplant related research.
3.Development history and challenges of sports and education integration in Chinese schools
Chinese Journal of School Health 2025;46(1):9-13
Abstract
The physical and mental health issues of children and adolescents in China are becoming increasingly prominent. Integrating physical education deeply into the educational system and maximizing its role in fostering personal development, preventing common illnesses among students, and promoting mental health has emerged as the intersection of school health and sports. The article systematically arranges the development history and patterns of physical education in Chinese schools, summarizes the existing difficulties in the integration of physical education and educational system, and presents improvement suggestions to provide a basis for enhancing the integration system and promote the comprehensive development of children and adolescents.
4.Dynamic observation of ophthalmic multimodal images after venous sinus stent placement in patients with idiopathic intracranial hypertension
Shuran WANG ; Dapeng MO ; Xiaofang LIANG ; Xu TONG ; Tao FU
Journal of Chinese Physician 2025;27(5):645-649
Objective:To explore the dynamic effects of venous sinus stenting (VSS) implantation on the optic nerve structure and visual function in patients with idiopathic intracranial hypertension (IIH).Methods:Patients with IIH combined with venous sinus stenosis and optic disc edema who were admitted to the Beijing Tiantan Hospital and received VSS treatment from January 2019 to September 2023 were prospectively included. Before the operation, the general data of the patients were collected and lumbar puncture examination was performed to measure the cerebrospinal fluid pressure. Ophthalmic multimodal imaging examinations such as binocular best corrected visual acuity (BCVA), optic disc stereoscopic photography, visual field, and optical coherence tomography (OCT) were performed respectively before the operation, 3 months and 6 months after the operation. The BCVA of both eyes, the Frisén grade (FPG) of optic disc edema, the mean defect (MD) value of the visual field, the thickness of the retinal nerve fiber layer (RNFL) around the optic disc and the thickness of the optic ganglion cell complex (GCC) were collected respectively. The eye with poor preoperative visual field MD value was defined as the study eye, and the other eye was the contralateral eye. The Friedman rank sum test was used to statistically analyze the differences of various indicators before the operation, 3 months after the operation and 6 months after the operation. Further, the Wilcoxon signed rank test was used to pairwise compare the results at the three time points.Results:A total of 72 patients with IIH who met the criteria were included, among whom 61 were female (84.7%), and the baseline optic disc edema Frisén grade was 3(2-4). The FPG, BCVA, MD values and RNFL thickness of the study eye and the contralateral eye at 3 and 6 months after the operation were significantly improved compared with those before the operation (all P<0.017). At 6 months after the operation, the FPG, BCVA, MD value, RNFL thickness of the study eye and the FPG and RNFL thickness of the contralateral eye were further improved compared with those at 3 months, and the differences were statistically significant (all P<0.017). During the treatment and follow-up period, no serious adverse reactions occurred in all patients. Conclusions:VSS can effectively improve papillary edema and visual function impairment in patients with IIH combined with venous sinus stenosis. Ophthalmic multimodal imaging examination provides an objective basis for preoperative assessment of optic nerve structure and visual function, postoperative efficacy monitoring and visual function recovery, etc. In the diagnosis and treatment process of IIH, the collaborative cooperation between the neurology department and the ophthalmology department is very important.
5.Differences in mercury dissolution from HgS-containing traditional medicines under simulated gastrointestinal conditions
Ming ZHANG ; Yuan-can XIAO ; Jing ZHAO ; Hai-ying TONG ; Xiao-yu WANG ; Wen-bin ZHOU ; Hong-tao BI ; Li-xin WEI
Chinese Traditional Patent Medicine 2025;47(8):2607-2611
AIM To investigate the variations in mercury dissolution from HgS-containing traditional medicines in three kinds of simulated gastrointestinal dissolution media.METHODS 39 batches of 15 types of HgS-containing traditional medicines were collected,total mercury content and dissolved mercury concentrations in simulated gastric fluid,simulated intestinal fluid,and L-cysteine-containing simulated intestinal fluid were measured.The maximum daily intake of total mercury and soluble mercury was calculated based on the maximum daily clinical dosage.RESULTS Among the 15 types of medicines,the maximum daily intake of total mercury varied by 156 times,the daily intake of soluble mercury varied by 3 502 times in simulated gastric fluid,313 times in simulated intestinal fluid,and 10 663 times in L-cysteine-containing simulated intestinal fluid,approximately.CONCLUSION For the 15 types of HgS-containing traditional medicines,the daily maximum intake of soluble mercury showed greater variations than that of total mercury.Soluble mercury concentration is more closely correlated with intestinal absorption of mercury and thus represents a more rational quality control indicator for HgS-containing traditional medicines.
6.Construction of risk nomogram of distant metastasis in gallbladder cancer based on the SEER database
Yingfei WEI ; Mengcheng WANG ; Tao MENG ; Zhong TONG
China Modern Doctor 2025;63(9):15-19,28
Objective To investigate the clinical factors affecting the risk of distant metastasis in patients with gallbladder carcinoma(GBC)and to construct a predictive model for metastasis risk.Methods Retrospective analysis was conducted on 4979 GBC patients from the surveillance,epidemiology,and end results(SEER)database from January 2000 to December 2021,which were divided into a training set(n=3485)and an internal validation set(n=1494)in a 7∶3 ratio.Additionally,47 GBC patients from Hefei First People's Hospital from January 2009 to December 2024 were collected as an external validation set.In the training set,univariate and multivariate analyses were performed to identify independent predictors of distant metastasis in GBC and to construct a predictive model.The predictive ability of the model was assessed by using area under the receiver operating characteristic curve.The model's calibration and clinical utility were evaluated through calibration curves and decision curve analysis.Results The results of univariate and multivariate analyses revealed that Caucasian,tumor size,T stage,and N stage were independent risk factors for distant metastasis in patients with GBC(P<0.05).The predictive model constructed based on these factors had an AUC of 0.727,indicating good predictive performance.In the training set,internal validation set,and external validation set,the predictive results of this model showed good consistency with the actual situation.Conclusion The nomogram established by using SEER database can accurately predict the distant metastasis status in patients with GBC and demonstrates good clinical applicability.It assists clinicians in intuitively assessing the distant metastasis rate in GBC patients,thereby facilitating the formulation of personalized treatment plans.
7.Dynamic observation of ophthalmic multimodal images after venous sinus stent placement in patients with idiopathic intracranial hypertension
Shuran WANG ; Dapeng MO ; Xiaofang LIANG ; Xu TONG ; Tao FU
Journal of Chinese Physician 2025;27(5):645-649
Objective:To explore the dynamic effects of venous sinus stenting (VSS) implantation on the optic nerve structure and visual function in patients with idiopathic intracranial hypertension (IIH).Methods:Patients with IIH combined with venous sinus stenosis and optic disc edema who were admitted to the Beijing Tiantan Hospital and received VSS treatment from January 2019 to September 2023 were prospectively included. Before the operation, the general data of the patients were collected and lumbar puncture examination was performed to measure the cerebrospinal fluid pressure. Ophthalmic multimodal imaging examinations such as binocular best corrected visual acuity (BCVA), optic disc stereoscopic photography, visual field, and optical coherence tomography (OCT) were performed respectively before the operation, 3 months and 6 months after the operation. The BCVA of both eyes, the Frisén grade (FPG) of optic disc edema, the mean defect (MD) value of the visual field, the thickness of the retinal nerve fiber layer (RNFL) around the optic disc and the thickness of the optic ganglion cell complex (GCC) were collected respectively. The eye with poor preoperative visual field MD value was defined as the study eye, and the other eye was the contralateral eye. The Friedman rank sum test was used to statistically analyze the differences of various indicators before the operation, 3 months after the operation and 6 months after the operation. Further, the Wilcoxon signed rank test was used to pairwise compare the results at the three time points.Results:A total of 72 patients with IIH who met the criteria were included, among whom 61 were female (84.7%), and the baseline optic disc edema Frisén grade was 3(2-4). The FPG, BCVA, MD values and RNFL thickness of the study eye and the contralateral eye at 3 and 6 months after the operation were significantly improved compared with those before the operation (all P<0.017). At 6 months after the operation, the FPG, BCVA, MD value, RNFL thickness of the study eye and the FPG and RNFL thickness of the contralateral eye were further improved compared with those at 3 months, and the differences were statistically significant (all P<0.017). During the treatment and follow-up period, no serious adverse reactions occurred in all patients. Conclusions:VSS can effectively improve papillary edema and visual function impairment in patients with IIH combined with venous sinus stenosis. Ophthalmic multimodal imaging examination provides an objective basis for preoperative assessment of optic nerve structure and visual function, postoperative efficacy monitoring and visual function recovery, etc. In the diagnosis and treatment process of IIH, the collaborative cooperation between the neurology department and the ophthalmology department is very important.
8.Cost-Effectiveness Analysis of Three Access Bronchoscopy in the Treatment of Central Airway Stenosis
Tong-tong HUANG ; Ying XIN ; Shangyang LUAN ; Tao XU ; Kuixu LAN
Chinese Health Economics 2025;44(10):80-83
Objective:To evaluate the cost-effectiveness of interventional bronchoscopy with rigid bronchoscopy(scleroscope),laryngeal mask airway and endotracheal intubation access for the treatment of central airway stenosis.Methods:The data of patients with central airway stenosis who underwent interventional bronchoscopy under general anesthesia were collected,and divided into rigid bronchoscopy group,laryngeal mask group and tracheal intubation group.The average Cost-Effectiveness Ratio(CER)was calculated using total hospitalization cost and total surgery cost as the cost indices,and improvement of shortness of breath symptoms as the effect index.The stability of the evaluation result was analyzed by one-factor sensitivity analysis and probabilistic sensitivity analysis.Results:A total of 205 patients were included:rigid bronchoscopy group(66 patients),laryngeal mask group(64 patients)and tracheal intubation group(75 patients).The CERs were 8 851.29 for the rigid bronchoscopy group,10 942.62 for the laryngeal mask group,and 8 902.98 for the tracheal intubation group when using total hospitalization cost as the cost index.For total surgery cost,the CERs were 2 617.80,3 389.73,and 2 741.38,respectively.The order was rigid bronchoscopy<tracheal intubation<laryngeal mask.The main factors affecting the model results were the discount rate,non-surgical costs,and improvement of shortness of breath symptoms.Probabilistic sensitivity analysis shows that the results of the basic analysis are stable.Conclusion:Interventional bronchoscopy via rigid bronchoscope is the most economical method for treating central airway stenosis.
9.Construction of CD8+T cell-associated Risk Model in Hepatocellular Carcinoma Based on Bulk and Single-cell RNA-seq Data
Xin-Tong ZHANG ; Jian-Jun ZHU ; Jin WU ; Hao WU ; Fan LU ; Wen-Tao ZHANG ; Jing-Jia CHANG ; Ting TANG ; Zhi-Gao OU ; Feng-Feng JIA ; Li LI ; Peng-Fei YU ; Ming LIU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(10):1511-1528
Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P<0.0001)and lower CD8+T cells infiltration(P<0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P<0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.
10.Cost-Effectiveness Analysis of Three Access Bronchoscopy in the Treatment of Central Airway Stenosis
Tong-tong HUANG ; Ying XIN ; Shangyang LUAN ; Tao XU ; Kuixu LAN
Chinese Health Economics 2025;44(10):80-83
Objective:To evaluate the cost-effectiveness of interventional bronchoscopy with rigid bronchoscopy(scleroscope),laryngeal mask airway and endotracheal intubation access for the treatment of central airway stenosis.Methods:The data of patients with central airway stenosis who underwent interventional bronchoscopy under general anesthesia were collected,and divided into rigid bronchoscopy group,laryngeal mask group and tracheal intubation group.The average Cost-Effectiveness Ratio(CER)was calculated using total hospitalization cost and total surgery cost as the cost indices,and improvement of shortness of breath symptoms as the effect index.The stability of the evaluation result was analyzed by one-factor sensitivity analysis and probabilistic sensitivity analysis.Results:A total of 205 patients were included:rigid bronchoscopy group(66 patients),laryngeal mask group(64 patients)and tracheal intubation group(75 patients).The CERs were 8 851.29 for the rigid bronchoscopy group,10 942.62 for the laryngeal mask group,and 8 902.98 for the tracheal intubation group when using total hospitalization cost as the cost index.For total surgery cost,the CERs were 2 617.80,3 389.73,and 2 741.38,respectively.The order was rigid bronchoscopy<tracheal intubation<laryngeal mask.The main factors affecting the model results were the discount rate,non-surgical costs,and improvement of shortness of breath symptoms.Probabilistic sensitivity analysis shows that the results of the basic analysis are stable.Conclusion:Interventional bronchoscopy via rigid bronchoscope is the most economical method for treating central airway stenosis.


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