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.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.
3.Extracorporeal blood purification therapy for acute poisoning in Jiangsu Province, China: a cross-sectional, multicenter real-world study
Li QIAO ; Jinsong ZHANG ; Jianrong CHEN ; Lijun LIU ; Ping GENG ; Hong SUN ; Yeping DU ; Zhiguang TIAN ; Jianjun MA ; Rushan YANG ; Jiancheng DONG ; Zheng QIN ; Shanshan WU ; Yumin PAN ; Yigang WU
Chinese Journal of Emergency Medicine 2025;34(3):369-375
Objective:To investigate the current application of blood purification in the treatment of acute poisoning within Jiangsu Province and to evaluate the impact of extracorporeal blood purification on the clinical outcomes of critically poisoned patients.Methods:This multicenter, cross-sectional real-world observational study followed patients presenting with poisoning to the emergency departments of nine hospitals in Jiangsu Province between June 2015 and May 2019. Data were collected on demographic characteristics, vital signs within the first hour of emergency presentation, treatment modalities, length of hospital stay, and survival outcomes. Clinical data from patients who underwent extracorporeal blood purification were compared with those who did not, using the Wilcoxon rank-sum test and Chi-square test.Results:A total of 4 178 poisoning cases were included between June 2015 and May 2019. Among them, 21.7% (908/4 178) received blood purification therapy, while 78.3% (3 270/4 178) did not. Hemoperfusion (90.4%) was the most frequently employed method, followed by continuous renal replacement therapy (CRRT) (4.4%). In combined blood purification modalities, 4.8% underwent hemoperfusion combined with CRRT, 0.1% received hemoperfusion with plasma exchange, and another 0.1% underwent hemoperfusion combined with both CRRT and plasma exchange. Among patients who underwent blood purification, pesticide poisoning was the most prevalent (76.3%), with the most common toxic agents being paraquat (23.7%), dichlorvos (8.7%), methamidophos (5.2%), omethoate (4.0%), and glyphosate (3.7%). Compared to the non-blood purification group, patients in the blood purification group were more likely to present within the first hour with a low Glasgow Coma Scale (GCS) score (3-8) (22.6% vs. 9.7%, P <0.05), low mean arterial pressure (8.0% vs. 3.2%, P <0.05), longer hospital stays [5(3,9) days vs. 2(1,4) days, P <0.05] and a higher in-hospital mortality rate (21.1% vs. 5.3%, P <0.05). Follow-up via telephone 28 days after discharge revealed a survival rate of 78.9%, with a mortality rate of 21.1% in the blood purification group. Conclusions:Hemoperfusion is the most commonly utilized blood purification technique for treating poisoning in Jiangsu Province, with pesticides being the primary toxic agents treated. Although the mortality rate is higher in the blood purification group, the intervention may still contribute to improved patient outcomes.
4.Optimization of extraction process for Bletillae Rhizoma and evaluation of its anti-oxidant,tyrosinase inhibitory activities
Shan-shan WANG ; Yi-yuan LUO ; Ye-fei XIE ; Xin-miao JIANG ; Ping PAN ; Kun-ming QIN ; Hong-jiang CHEN
Chinese Traditional Patent Medicine 2025;47(7):2171-2177
AIM To optimize the extraction process for Bletillae Rhizoma,and to evaluate its anti-oxidant,tyrosinase inhibitory activities.METHODS With ultrasound time,ethanol concentration and solid-liquid ratio as influencing factors,the total extraction content of gastrodin,protocatechualdehyde,p-hydroxybenzaldehyde,1,4-bis[4-(gluconoxy)benzyl]-2-isobutylmalate-2-glucoside,1,4-bis[4-(gluconoxy)benzyl]-2-isobutylmalate,yam Ⅲ,dihydropinosin and 3'-O-methylyam Ⅲ as an evaluation index,the extraction process was optimized by Box-Behnken response surface method.Subsequently,the extract's scavenging effects on DPPH,ABTS+free radicals,and inhibitory ability on tyrosinase were determined.RESULTS The optimal conditions were determined to be 49 min for ultrasound time,55%for ethanol concentration,1∶30 for solid-liquid ratio,and 2 times for extraction frequency,the total extraction content was 13.18 mg/g.The extract demonstrated the IC50 of 10.12,314.07 and 1.70 μg/g on DPPH,ABTS+free radicals and tyrosinase,respectively.CONCLUSION This simple,reliable and stable method can be used for the extraction for Bletillae Rhizoma with strong anti-oxidant,tyrosinase inhibitory activities.
5.Astragaloside Ⅳ attenuates pathological myocardial hypertrophy and fibrosis in mice via EGR1-SIRT1-PPARα-SCAD signaling pathway
Li-yuan QING ; Lan-ting LIU ; Qing-ping XU ; Huan PENG ; Yu-hong CAO ; Xue-diao PAN ; Si-gui ZHOU
Chinese Pharmacological Bulletin 2025;41(2):242-250
Aim To elucidate whether Astragaloside Ⅳcould ameliorate pathological myocardial hypertrophy and fibrosis via the EGR1-SIRT1-PPARα-SCAD signa-ling pathway in TAC mice.Methods After randomi-zing mice into groups,the Sham+AS-Ⅳ group and TAC+AS-Ⅳ group were intragastrically administered 20 mg·kg-1AS-Ⅳ once daily,whereas the Sham+NS group and TAC+NS group were given equivalent saline.Six weeks post-surgery,an evaluation of cardiac function was conducted,heart weight index was compu-ted,morphological alterations in heart were noted,vari-ations in collagen and myocardial hypertrophy indexes were analyzed,ATP content,free fatty acid content,hydroxyproline content,SCAD expression,and enzyme activity were measured,and an initial investigation into the protein expression of EGR1-SIRT1-PPARα-SCAD in myocardial tissues was undertaken.Results After AS-Ⅳ intervention,the heart weight index of TAC mice decreased(P<0.01),LVAWd,LVAWs,LVPWd and LVPWs values decreased(P<0.01,P<0.05),EF%and FS%values increased(all P<0.01),myocardial hypertrophy markers and collagen area decreased,FFA content,HYP content and collagen expression de-creased(all P<0.01),SCAD enzyme activity and ex-pression increased(P<0.01,P<0.05),and ATP content increased(P<0.01).The expression of EGR1 protein decreased,and the expression of SIRT1 and PPARα protein increased(all P<0.01).Conclu-sions AS-Ⅳ may improve fatty acid oxidation via the EGR1-SIRT1-PPARα-SCAD signaling pathway,thereby ameliorating pathological myocardial hypertrophy and fibrosis in TAC model mice.
6.Current status and prospects for screening early-stage hepatocellular carcinoma
Haolin SONG ; Shoufeng JIANG ; Xue YANG ; Xiaoxiao YAO ; Chenwei PAN ; Ping CHEN
Chinese Journal of Hepatology 2025;33(1):70-76
Hepatocellular carcinoma is the most common type of primary liver cancer. Many patients who have been diagnosed with hepatocellular carcinoma are already at an advanced stage, leading to very limited treatment options and poor prognosis. Therefore, the key to improving prognosis is early-stage diagnosis. In recent years, with deeper analysis of the underlying biological mechanisms of HCC, new diagnostic methods have emerged, including emerging serum markers, liquid biopsy, molecular diagnostics, and imaging techniques. This article reviews and analyzes the research progress on early-stage screening and explores their value and application prospects in the early predictive diagnosis of HCC..
7.Symptoms and quality of life benefits of successful percutaneous coronary intervention in left main disease and/or 3-vessel disease patients with diabetes
Bo-da ZHU ; Tian-tong YU ; Peng HAN ; Bo-hui ZHANG ; Xi ZHANG ; Ping YUAN ; Gang WANG ; Yi YANG ; Hui-li ZHU ; Pan-pan SUN ; Tong-tong LI ; Shuai ZHAO ; Cheng-xiang LI ; Kun LIAN
Chinese Journal of Interventional Cardiology 2025;33(2):93-100
Objective To investigate whether successful percutaneous coronary intervention(PCI)could improve symptoms and quality of life(QOL)in left main disease and/or 3-vessel disease patients with diabetes.Methods Patients with left main disease and/or 3-vessel disease who underwent PCI in the First Affiliated Hospital of Air Force Medical University from April 2018 to May 2021 were consecutively enrolled and subdivided into 2 groups:diabetes and no diabetes.Detailed baseline characteristics,symptoms,including dyspnea and angina,assessed with the Rose dyspnea scale(RDS),Seattle angina questionnaire(SAQ),the European quality of life-5 dimensions(EQ-5D)and 12-item short-form health survey(SF-12)questionnaire respectively,procedural details,and 1 month and 1 year follow-up data were collected.Results Among 440 left main disease and/or 3-vessel disease patients,disease was present in 176(40.00%),who had more hypertension,peripheral artery disease,and LCX lesion(all P<0.05).The incidence of major adverse cardiovascular events(MACE)and all-cause mortality were similar between the two groups(both P>0.05)at 1 month follow-up,while all-cause mortality in diabetes patients was significantly higher than those without diabetes at 1 year follow-up(P=0.013).Low left ventricular ejection fraction was an independent risk factor for MACE and all-cause mortality at 1 month and 1 year follow-up after successful revascularization(all P<0.05).Most importantly,symptoms,including dyspnea and angina,and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up(all P<0.05).Diabetes patients showed improved dyspnea and QOL at similar degree to the non-diabetes patients(all P>0.05)and a more significantly relieved angina(P=0.013).Additionally,the number of chronic total occlusion(CTO)per patient was identified as an independent risk factor of dyspnea(OR 0.723,95%CI 0.525~0.997,P=0.048)and angina relief(OR 0.686,95%CI 0.473~0.995,P=0.047),and the contrast volume(OR 0.995,95%CI 0.992~0.999,P=0.008)as an independent risk factor of QOL improvement in diabetic patients.Conclusions Successful PCI is beneficial for relieving symptoms and improving quality of life in patients with diabetes who have left main disease and/or 3-vessel disease.
8.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.
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*
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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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