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.Nasal nitric oxide in preschool children with chronic rhinosinusitis
Meiling WU ; Jiewei LIU ; Ping LIU ; Rifu WEI ; Shang GAO ; Huifeng LI ; Xiaochun PAN
Chinese Archives of Otolaryngology-Head and Neck Surgery 2025;32(7):451-454
OBJECTIVE Analyze the nasal nitric oxide(NNO)of CRS children,and explore the clinical value of NNO in the diagnosis and treatment of CRS in children.METHODS CRS children diagnosed in the outpatient clinic were selected,and were divided into CRS with and without AR according to their allergen results.VAS score and NNO test were performed for them.Healthy children during the same period were selected as the control group.Finally their results were compared and analyzed.RESULTS The NNO of CRS children with and without AR were(193±62)ppb and(138±49)ppb,both lower than the control group's[(243±51)ppb];There were negative correlations between NNO and VAS scores in CRS children without AR before and after treatment;The NNO of CRS children with and without AR were significantly increased after treatment(P<0.05);NNO has high predictive value for diagnosing CRS children without AR(P<0.01).CONCLUSION The levels of NNO in different types of CRS were lower than normal,and CRS children without AR was lower than those with AR.NNO could assist in the diagnosis of CRS,dynamically reflect the severity of nasal inflammation,and help to distinguish the allergic status of CRS.
3.Influencing factors of prognosis and nursing strategies in sepsis combined with gastrointestinal dysfunction
Weihong PAN ; Bojun ZHENG ; Ping CAO
Journal of Navy Medicine 2025;46(6):609-613
Objective To explore the influencing factors of prognosis and nursing strategies in sepsis combined with gastrointestinal dysfunction.Methods The clinical data of 102 patients with sepsis and gastrointestinal dysfunction who were admitted to Traditional Chinese Medicine Hospital of Guangdong Province(The Second Affiliated Hospital of Guangzhou University of Chinese Medicine)between June 2022 and December 2023 were retrospectively analyzed.According to the prognosis within 30 d,the patients were assigned to death group(n=38)or survival group(n=64).Clinical indexes were compared between the two groups.The main influencing factors of prognosis were analyzed by Logistic regression,and targeted nursing strategies were summarized.Results The mortality in the patients with sepsis and gastrointestinal dysfunction was 37.25%(38/102).Univariate analysis showed that age,Sequential Organ Failure Assessment(SOFA)score,Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score,gastrointestinal failure(GIF)score,and stay time in ICU were all influencing factors of prognosis in patients with sepsis and gastrointestinal dysfunction(all P<0.05).Logistic regression analysis showed that age≥65 years,SOFA score>6,APACHEⅡscore>17,GIF score>3,and stay time in ICU>7 d were independent risk factors of poor prognosis in patients with sepsis and gastrointestinal dysfunction(all P<0.05).Conclusion The poor prognosis of patients with sepsis and gastrointestinal dysfunction is related to age,SOFA score,APACHEⅡscore,GIF score,and stay time in ICU.It is essential to take preventive and nursing measures for these risk factors to reduce the incidence of poor prognosis.
4.Network Pharmacology and Experimental Verification Unraveled The Mechanism of Pachymic Acid in The Treatment of Neuroblastoma
Hang LIU ; Yu-Xin ZHU ; Si-Lin GUO ; Xin-Yun PAN ; Yuan-Jie XIE ; Si-Cong LIAO ; Xin-Wen DAI ; Ping SHEN ; Yu-Bo XIAO
Progress in Biochemistry and Biophysics 2025;52(9):2376-2392
ObjectiveTraditional Chinese medicine (TCM) constitutes a valuable cultural heritage and an important source of antitumor compounds. Poria (Poria cocos (Schw.) Wolf), the dried sclerotium of a polyporaceae fungus, was first documented in Shennong’s Classic of Materia Medica and has been used therapeutically and dietarily in China for millennia. Traditionally recognized for its diuretic, spleen-tonifying, and sedative properties, modern pharmacological studies confirm that Poria exhibits antioxidant, anti-inflammatory, antibacterial, and antitumor activities. Pachymic acid (PA; a triterpenoid with the chemical structure 3β-acetyloxy-16α-hydroxy-lanosta-8,24(31)-dien-21-oic acid), isolated from Poria, is a principal bioactive constituent. Emerging evidence indicates PA exerts antitumor effects through multiple mechanisms, though these remain incompletely characterized. Neuroblastoma (NB), a highly malignant pediatric extracranial solid tumor accounting for 15% of childhood cancer deaths, urgently requires safer therapeutics due to the limitations of current treatments. Although PA shows multi-mechanistic antitumor potential, its efficacy against NB remains uncharacterized. This study systematically investigated the potential molecular targets and mechanisms underlying the anti-NB effects of PA by integrating network pharmacology-based target prediction with experimental validation of multi-target interactions through molecular docking, dynamic simulations, and in vitro assays, aimed to establish a novel perspective on PA’s antitumor activity and explore its potential clinical implications for NB treatment by integrating computational predictions with biological assays. MethodsThis study employed network pharmacology to identify potential targets of PA in NB, followed by validation using molecular docking, molecular dynamics (MD) simulations, MM/PBSA free energy analysis, RT-qPCR and Western blot experiments. Network pharmacology analysis included target screening via TCMSP, GeneCards, DisGeNET, SwissTargetPrediction, SuperPred, and PharmMapper. Subsequently, potential targets were predicted by intersecting the results from these databases via Venn analysis. Following target prediction, topological analysis was performed to identify key targets using Cytoscape software. Molecular docking was conducted using AutoDock Vina, with the binding pocket defined based on crystal structures. MD simulations were performed for 100 ns using GROMACS, and RMSD, RMSF, SASA, and hydrogen bonding dynamics were analyzed. MM/PBSA calculations were carried out to estimate the binding free energy of each protein-ligand complex. In vitro validation included RT-qPCR and Western blot, with GAPDH used as an internal control. ResultsThe CCK-8 assay demonstrated a concentration-dependent inhibitory effect of PA on NB cell viability. GO analysis suggested that the anti-NB activity of PA might involve cellular response to chemical stress, vesicle lumen, and protein tyrosine kinase activity. KEGG pathway enrichment analysis suggested that the anti-NB activity of PA might involve the PI3K/AKT, MAPK, and Ras signaling pathways. Molecular docking and MD simulations revealed stable binding interactions between PA and the core target proteins AKT1, EGFR, SRC, and HSP90AA1. RT-qPCR and Western blot analyses further confirmed that PA treatment significantly decreased the mRNA and protein expression of AKT1, EGFR, and SRC while increasing the HSP90AA1 mRNA and protein levels. ConclusionIt was suggested that PA may exert its anti-NB effects by inhibiting AKT1, EGFR, and SRC expression, potentially modulating the PI3K/AKT signaling pathway. These findings provide crucial evidence supporting PA’s development as a therapeutic candidate for NB.
5.Efficacy and safety of modified Shenqi Maiwei Dihuang Decoction combined with Buzhong Yiqi Pill in treatment of cold and heat mixed type diabetic foot
Yinfeng XIA ; Weiwei CHEN ; Ping WU ; Yongsong CHEN ; Jie LIU ; Jianxiang PAN ; Zhiyong CHEN
Chongqing Medicine 2025;54(2):387-392
Objective To compare the therapeutic effects of modified Shenqi Maiwei Dihuang Decoction combined with Buzhong Yiqi Pill and Buzhong Yiqi pill alone in the patients with cold and heat mixed type di-abetic foot.Methods A total of 123 patients with cold and heat mixed type diabetic foot receiving the treat-ment in this hospital from April 2022 to December 2023 were selected and divided into the modified Shenqi Mai-Dihuang Decoction and Buzhong Yiqi Pill group(combined group,60 cases)and Buzhong Yiqi Pill group(monotherapy group,63 cases).The wound healing,mean blood flow amount of foot dorsal artery,blood glu-cose and changes in vascular diameter,inflammatory factors and vascular endothelial growth factor after 2 courses of treatment were compared betweeb the 2 groups.Results The ulcer reduction rate in the combina-tion group was significantly higher than that in the monotherapy group(P=0.001).The fasting blood glu-cose and 2 h postprandial blood glucose after treatment in the combination group all were lower than those in the monotherapy group(P=0.001).The average blood flow of foot dorsal artery after treatment in combina-tion group was higher than that in the monotherapy group,and the difference was statistically significant(P=0.013).There were 34 cases of Wagner grade 3 in the combined group and 33 cases of Wagner grade 3 in the monotherapy subgroup respectively.There was statistically significant difference in the CRP level between the two subgroups(P=0.045).Conclusion Shenqi Maiwei Dihuang Decoction combined with Buzhong Yiqi Pill in treating diabetic foot ulcer is more effective than Buzhong Yiqi Pill alone,moreover the safety is high.
6.Meta-analysis of the clinical efficacy and safety of Jianwei xiaoshi oral liquid in the treatment of functional dyspepsia in children
Ping RONG ; Guiyun PAN ; Juan WEI ; Tengda LI ; Xilian ZHANG
China Pharmacy 2025;36(7):867-873
OBJECTIVE To evaluate the clinical efficacy and safety of Jianwei xiaoshi oral liquid in the treatment of functional dyspepsia (FD) in children, and provide evidence-based basis for clinical use of the drug. METHODS Retrieved from CNKI, VIP, Wanfang, CBM, Cochrane Library and PubMed, randomized controlled trials (RCTs) about Jianwei xiaoshi oral liquid in the treatment of FD in children were collected from the inception to Apr. 2024. The control group was treated with conventional western drugs (including gastrointestinal motion-promoting, antacids or acid-suppressing drugs), and the trial group was treated with Jianwei xiaoshi oral liquid alone or combined with conventional Western drugs (drug dosage and course of treatment were the same as the control group). Meta-analysis was performed using RevMan 5.3 software after quality evaluation with the Cochrane risk bias assessment tool 6.1. RESULTS Totally 16 literature were employed which included 1 962 patients. The results of meta-analysis showed that the total clinical effective rate of Jianwei xiaoxi oral liquid in the treatment of FD in children of trial group was significantly higher than that of the control group [RR=1.18, 95%CI (1.13, 1.22), P<0.000 01]. In this study, subgroup analysis was conducted on the usage and dosage, course of treatment, and combination or not in trial group, as well as the type of conventional Western drugs. The results showed that the total clinical effective rate of trial group was significantly higher than that of control group; the relief time of abdominal distension and abdominal pain in trial group [MD=-2.54, 95%CI (-3.10, -1.98)], loss of appetite relief time [MD=-2.12, 95%CI (-2.63, -1.61)], nausea and vomiting relief time [MD=-1.70, 95%CI (-2.27, -1.14)], and belching relief time [MD=-1.61, 95%CI (-2.44, -0.78)] were shorter than that of the control group significantly (P<0.05). In addition, compared with control group, the levels of gastrin [SMD=1.63, 95%CI (0.98, 2.29)] and motilin [SMD=2.06, 95%CI (1.58, 2.54)] as well as gastric antral emptying rate [MD=5.99, 95%CI (2.78, 9.21)] in trial group were increased significantly, while the level of somatostatin was decreased significantly [SMD=-1.30, 95%CI (-1.57, -1.02)] (P≤0.000 3). CONCLUSIONS Jianwei xiaoshi oral liquid, whether used alone or in combination with other medications, and regardless of the treatment course or dosage and usage, is effective in treating FD in children, with good safety.
7.Association Between Vitamin D Status and Insulin Resistance in Adolescents: A Cross-sectional Observational Study
Xiaoyuan GUO ; Yutong WANG ; Zhibo ZHOU ; Shi CHEN ; Mei ZHANG ; Bo BAN ; Ping LI ; Xinran ZHANG ; Qiuping ZHANG ; Kai YANG ; Hongbo YANG ; Hanze DU ; Hui PAN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):577-583
To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents. This cross-sectional observational study employed convenience sampling to recruit 2021-grade(8th grade) students from Jining No.7 Middle School in Shandong Province on June 5, 2023. Data collection included questionnaires, physical examinations, and imaging assessments to obtain general information, secondary sexual characteristics development, and bone age. Venous blood samples were collected to measure fasting blood glucose(FBG), fasting insulin(FINS), homeostasis model assessment of insulin resistance(HOMA-IR), and 25-hydroxyvitamin D[25(OH)D] levels. Spearman correlation analysis and multivariate linear regression models were used to examine the associations between serum vitamin D levels and FBG, FINS, and HOMA-IR. The study included 168 pubertal adolescents[69 females(41.1%), 99 males(58.9%); mean age(13.27±0.46) years]. All participants had entered puberty based on sexual development assessment. Vitamin D deficiency was observed in 41 participants(24.4%), insufficiency in 109(64.9%), and sufficiency in 18(10.7%). The median HOMA-IR was 3.49(2.57, 5.14).Significant differences were found across vitamin D status groups for HOMA-IR [4.45(2.54, 6.62) Vitamin D deficiency/insufficiency is prevalent among pubertal adolescents, and serum vitamin D levels show a significant inverse association with insulin resistance. These findings suggest the potential importance of vitamin D status in metabolic health during puberty.
8.Body Composition Profiles and Associated Factors in Adolescents UndergoingLong-term Regular Exercise
Yutong WANG ; Xiaoyuan GUO ; Hanze DU ; Hui PAN ; Wei WANG ; Mei ZHANG ; Bo BAN ; Ping LI ; Xinran ZHANG ; Qiuping ZHANG ; Hongshuang SUN ; Rong LI ; Shi CHEN
Medical Journal of Peking Union Medical College Hospital 2025;16(3):591-597
To investigate body composition and associated factors in adolescents undergoing long-term regular sports training. This prospective longitudinal cohort study employed convenience sampling to recruit adolescents receiving structured athletic training at Jining Sports Training Center in June 2023. Baseline measurements included height, weight, body mass index (BMI), blood pressure, heart rate, waist circumference, and hip circumference. Questionnaires assessed sleep duration, screen time, and household income. Follow-up measurements in June 2024 repeated these assessments while adding bioelectrical impedance analysis for body composition (lean mass, skeletal muscle mass, fat mass, and body fat percentage). Linear regression models examined associations between training type (direct-contact vs. non-contact sports) and follow-up body fat percentage, BMI, and waist circumference as dependent variables, adjusting for covariates. The study included 110 adolescents (39 female, 71 male) with median age 13.21 years (IQR: 12.46-14.33). Participants comprised 65 direct-contact and 45 non-contact athletes. Baseline prevalence rates were 27.27% for overweight/obesity, 24.55% for elevated waist circumference, and 16.36% for elevated blood pressure. At follow-up, corresponding rates were 24.55%, 26.36%, and 13.64% respectively. The elevated blood pressure subgroup showed significantly higher waist circumference ( Despite regular athletic training, substantial proportions of adolescents exhibited overweight/obesity, abdominal obesity, and elevated blood pressure, warranting clinical attention. Training modality appears to influence body composition changes, with direct-contact sports associated with more favorable adiposity-related outcomes.
10.(Meta)transcriptomic Insights into the Role of Ticks in Poxvirus Evolution and Transmission: A Multicontinental Analysis.
Yu Xi WANG ; Jing Jing HU ; Jing Jing HOU ; Xiao Jie YUAN ; Wei Jie CHEN ; Yan Jiao LI ; Qi le GAO ; Yue PAN ; Shui Ping LU ; Qi CHEN ; Si Ru HU ; Zhong Jun SHAO ; Cheng Long XIONG
Biomedical and Environmental Sciences 2025;38(9):1058-1070
OBJECTIVE:
Poxviruses are zoonotic pathogens that infect humans, mammals, vertebrates, and arthropods. However, the specific role of ticks in transmission and evolution of these viruses remains unclear.
METHODS:
Transcriptomic and metatranscriptomic raw data from 329 sampling pools of seven tick species across five continents were mined to assess the diversity and abundance of poxviruses. Chordopoxviral sequences were assembled and subjected to phylogenetic analysis to trace the origins of the unblasted fragments within these sequences.
RESULTS:
Fifty-eight poxvirus species, representing two subfamilies and 20 genera, were identified, with 212 poxviral sequences assembled. A substantial proportion of AT-rich fragments were detected in the assembled poxviral genomes. These genomic sequences contained fragments originating from rodents, archaea, and arthropods.
CONCLUSION
Our findings indicate that ticks play a significant role in the transmission and evolution of poxviruses. These viruses demonstrate the capacity to modulate virulence and adaptability through horizontal gene transfer, gene recombination, and gene mutations, thereby promoting co-existence and co-evolution with their hosts. This study advances understanding of the ecological dynamics of poxvirus transmission and evolution and highlights the potential role of ticks as vectors and vessels in these processes.
Animals
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Poxviridae/physiology*
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Ticks/virology*
;
Phylogeny
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Transcriptome
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Evolution, Molecular
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Poxviridae Infections/virology*
;
Genome, Viral

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