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.

Objective To give references for future study,the current state of research and identify key areas of interest,and development trends in the field of Chinese Materia Medica interventions for PD were examined.Methods Literature on Chinese Materia Medica treatment of PD published between 2004 and 2024 was retrieved from the China National Knowledge Infrastructure(CNKI)and Web of Science(WOS)databases.After screening,689 articles were included(412 in Chinese,277 in English).CiteSpace software was used for bibliometric and knowledge graph analysis,generating author collaboration networks,institutional collaboration networks,keyword clustering,timeline maps,and keyword burst analysis.Results Over the past two decades,the number of publications has continued to grow globally.Chinese-language studies focused primarily on clinical research,with core authors such as Yi Liu,Jiancheng He,and Jianfen Liang,and institutions like Guangxi University of Chinese Medicine making significant contributions.English-language literature emphasized mechanistic studies,with Kyung Hee University and Beijing University of Chinese Medicine as leading research teams.High-frequency keywords included"Parkinson's disease"(346 occurrences),"traditional Chinese medicine(TCM)"(60 occurrences),and"oxidative stress"(11 occurrences).Keyword clustering revealed research hotspots in TCM formulas(e.g.,Zhichan decoction),mechanisms(e.g.,oxidative stress),and integrated TCM-Western medicine therapies(e.g.,Madopar).Burst analysis indicated emerging frontiers in the gut-brain axis,iron metabolism,molecular docking,gut microbiota,and signaling pathways.Conclusions Although there is a lot of potential for treating PD in TCM,there are also a lot of challenges.In order to realize the transformation of TCM from a supportive to a mainstream treatment for PD,and to bring better efficacy to patients in the future,it is necessary to strengthen evidence-based research,deepen the research of mechanisms,promote the construction of standards,explore the integration of Chinese and Western medicine,and improve the evaluation system.

We took the surface spike S protein of transmissible gastroenteritis virus(TGEV)as the research object.Based on the Gram-positive enhancer matrix(GEM)-anchor protein(PA)display platform,two kinds of bacteria-like particles(BLPs)with surface-displayed TGEV DA and S1 were prepared using the insect cell-baculovirus expression system.The results showed that the lev-els of IL-4,IFN-γ,IgG,IgA,and sIgA induced by 50 μg BLP-DA were higher than those of the 25μg group.The levels of IL-4,IFN-γ,and sIgA induced by 50 μg BLP-S1 were higher than those of the 25 μg group,while the levels of IgG and IgA were lower than those of the 25 μg group.Under the same dose,when the dose was 25 μg,the levels of IFN-γ,IgG,IgA,and sIgA induced by BLP-S1 were higher than those of BLP-DA,while the level of IL-4 was lower than that of BLP-DA.When the dose was 50 μg,the level of IgG induced by BLP-DA was higher than that of BLP-S1,while the other indicators were lower than those of BLP-S1.Under different immunization routes,the levels of IgA and sIgA in the gavage group were higher than those in the intramuscular injec-tion group,and the levels of some cytokines were significantly higher in the gavage group than in the intramuscular injection group at specific time points,but there was no significant difference in the levels of IgG antibodies.In conclusion,the two types of TGEV BLPs constructed in this study both have good immunogenicity and can induce cellular and humoral immunity in mice.When the immunization doses are the same,the immunogenicity of BLP-S1 is better than that of BLP-DA.

We took the surface spike S protein of transmissible gastroenteritis virus(TGEV)as the research object.Based on the Gram-positive enhancer matrix(GEM)-anchor protein(PA)display platform,two kinds of bacteria-like particles(BLPs)with surface-displayed TGEV DA and S1 were prepared using the insect cell-baculovirus expression system.The results showed that the lev-els of IL-4,IFN-γ,IgG,IgA,and sIgA induced by 50 μg BLP-DA were higher than those of the 25μg group.The levels of IL-4,IFN-γ,and sIgA induced by 50 μg BLP-S1 were higher than those of the 25 μg group,while the levels of IgG and IgA were lower than those of the 25 μg group.Under the same dose,when the dose was 25 μg,the levels of IFN-γ,IgG,IgA,and sIgA induced by BLP-S1 were higher than those of BLP-DA,while the level of IL-4 was lower than that of BLP-DA.When the dose was 50 μg,the level of IgG induced by BLP-DA was higher than that of BLP-S1,while the other indicators were lower than those of BLP-S1.Under different immunization routes,the levels of IgA and sIgA in the gavage group were higher than those in the intramuscular injec-tion group,and the levels of some cytokines were significantly higher in the gavage group than in the intramuscular injection group at specific time points,but there was no significant difference in the levels of IgG antibodies.In conclusion,the two types of TGEV BLPs constructed in this study both have good immunogenicity and can induce cellular and humoral immunity in mice.When the immunization doses are the same,the immunogenicity of BLP-S1 is better than that of BLP-DA.

Objective:To investigate the correlation between carotid-femoral pulse wave velocity(cfPWV)and carotid artery structural,hemodynamic,and cardiac functional parameters.Methods:A total of 420 healthy volunteers who underwent neck ultrasound,cardiac ultrasound,and cfPWV examination at Kailuan General Hospital from June 2022 to February 2023 were selected,and they were divided into two groups based on the atherosclerosis threshold value of cfPWV>10 m/s,which included high cfPWV group(140 cases,cfPWV>10 m/s)and low cfPWV group(280 cases,cfPWV≤10 m/s).The demographic data(age,sex)of 420 persons were collected,and the common carotid artery diameter(CCAD),common carotid artery intima-media thickness(CIMT),plaque status,peak systolic velocity(PSV),end-diastolic velocity(EDV)and mean flow velocity(MFV)were compared between two groups.Then,the differences of interventricular septal thickness(IVST)of heart,left ventricular posterior wall thickness(LVPWT),the ratio of blood flow velocity at early stage to that at advanced stage in mitral valve(E/A)and stroke volume(SV)were analyzed.Multivariate logistic regression was adopted to analyze the independent influence factors of cfPWV enhancement.Results:The average age of high cfPWV group was(61.31±9.66)years old,which was significantly higher than(51.06±10.47)years old of low cfPWV group,and the difference of that was significant(t=-9.56,P<0.01).In the parameters of common carotid artery,63 persons(45.0%)occurred plaque in 140 persons of high cfPWV group,which was significantly lower than 50 persons(17.86%)in 280 persons of low cfPWV group,and the difference of that between two groups was significant(x2=34.97,P<0.05).The differences of CCAD,CIMT,PSV,EDV and MV of common carotid artery at right side of persons between two groups were significant(t=-2.16,-5.40,4.52,5.59,5.04,P<0.05),respectively.The parameters of heart showed that the LVPWT thickness increased(9.35±1.13)mm,and the ratio of E/A<1 increased 77.86%in high cfPWV group,which were significantly related to the increase of cfPWV(r=0.27,0.38,P<0.01).Multivariate logistic regression analysis indicated that age(OR=1.05,95%CI:1.02-1.08),CCAD(OR=1.63,95%CI:1.22-2.16),plaque presence(OR=1.84,95%CI:1.07-3.17),LVPWT(OR=1.35,95%CI:1.05-1.72),and the ratio of E/A<1(OR=2.37,95%CI:1.32-4.26)were independent predictors of cfPWV enhancement.Conclusion:The enhancement of cfPWV is closely related to high age,the reconstruction of common carotid artery(widening of inside diameter,and plaque formation),left ventricular hypertrophy,and diastolic abnormality,which indicates it is possible that atherosclerosis process accompanies by the change of interaction mechanism of blood vessels-heart.

Objective:To determine if preoperative 68Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/MR could contribute to predicting pathological complete response (pCR) in patients with gastrointestinal cancer undergoing neoadjuvant immunotherapy. Methods:In this retrospective study, 35 patients (23 males, 12 females, age (59.1±7.9) years) with gastrointestinal cancer who underwent 68Ga-FAPI-04 PET/MR after receiving neoadjuvant immunotherapy between February 2021 and January 2024 were enrolled. Clinical data, PET imaging parameters including SUV, peak of SUV normalized by lean body mass (SUL peak), FAPI-positive tumor volume (FTV), and total FAPI-positive lesion burden (TLF), and pathological data were collected and analyzed. Patients were divided into pCR group and non-pCR group, and the independent-sample t test or Mann-Whitney U test was performed to compare those parameters between the 2 groups. ROC curve analysis (Delong test) was performed to evaluate the diagnostic efficiency of each parameter to predict pCR. Results:The overall pCR rate of the neoadjuvant therapy was 40.0%(14/35). In the visual evaluation, 68Ga-FAPI-04 PET was limited in predicting pCR, showing false positivity in 12 patients and false negative in 1 patent. While SUV max( t=2.50, P=0.018), SUL peak( t=3.11, P=0.004), FTV( U=3.00, P=0.030) and TLF( U=2.96, P=0.042) in non-pCR group were all higher than those in pCR group. The predictive efficiency of FTV <1.925cm 3 for pCR was better than the efficiency of PET visual evaluation ( Z=3.61, P<0.001), with the prediction accuracy of 82.86%(29/35). Conclusions:68Ga-FAPI-04 PET/MR may provide an effective clinical tool for guiding further treatment of patients with gastrointestinal cancer undergoing neoadjuvant immunotherapy. The quantitative features derived from 68Ga-FAPI-04 PET appear promising in predicting pCR, which are expected to provide a reference for avoiding surgery.

Objective:To evaluate the clinical value of 11C-methyl- L-methionine (MET) PET/MR in the differential diagnosis between neoplastic and non-neoplastic brain lesions. Methods:From July 2017 to May 2022, a total of 34 patients (19 males, 15 females, age 8-81 years) who received 11C-MET PET/MR imaging for suspected brain tumors in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively enrolled. Postoperative pathological or clinical follow-up results were used as the gold standard. Diagnostic performance of 11C-MET PET/MR and contrast-enhanced MRI was evaluated by ROC curve analysis and Delong test, as well as the diagnostic performance of PET metabolic parameters (SUV and target to background ratio (TBR)), MRI multi-sequence parameters (cerebral blood flow (CBF), relative CBF (rCBF), apparent diffusion coefficient (ADC), relative ADC (rADC), choline/creatine (Cho/Cr) and choline/ N-acetylaspartate (Cho/NAA)) and their combination. Results:A total of 35 lesions of 34 patients were enrolled, including 12 (34.3%) non-neoplastic lesions and 23(65.7%) neoplastic lesions. The diagnostic sensitivity, specificity, and accuracy for 11C-MET PET/MR were 91.3%(21/23), 12/12, and 94.3%(33/35), in contrast to 16/18, 2/10, and 64.3%(18/28) for contrast-enhanced MRI. Maximum TBR (TBR max) showed the highest discriminative value (AUC=0.877, 95% CI: 0.692-1.000). The combination of TBR max, minimum ADC (ADC min), rCBF, and Cho/NAA could achieve a higher diagnostic performance (AUC=0.918, 95% CI: 0.816-1.000), although the difference was not statistically significant ( Z=-0.42, P=0.676). Conclusion:Multiple quantitative parameters of 11C-MET PET/MR are beneficial to distinguish neoplastic from non-neoplastic brain lesions, and their combination may improve the diagnostic confidence.

Objective:To examine the differences in the medical quality of elderly Medicare patients in tertiary public hospitals before and after the implementation of the Diagnosis-related Group Prospective Payment System(DRG-PPS), and to explore the establishment of a long-term quality control mechanism.Methods:A total of 62, 321 inpatient first-page records was collected from Beijing Hospital, including 27, 488 cases from January to December 2019 and 34, 833 cases from January to December 2023.Firstly, the two-sample Kolmogorov-Smirnov test was applied to six sample DRG groups to analyze the statistical differences in the intra-group indicators(average per-case cost, average length of stay)among three age groups(young and middle-aged group: 18-65 years old; early elderly group: 66-79 years old; advanced elderly group: 80-99 years old)before and after the DRG-PPS reform of the medical insurance payment system.Secondly, the two-sample Kruskal-Wallis test was used to analyze the statistical differences in the indicators(total cost, medical cost, nursing cost, medical technology cost, pharmaceutical cost, consumable cost, administrative cost, and length of stay)among the three age groups within the same DRG group.Finally, the Conover test was employed for pairwise comparisons of inter-group indicators between the three groups.Results:Through the intra-group analysis of the total cost and average length of stay indicators of different age groups in the six sample DRG groups( n=6, 248), it was found that the differences were statistically significant.( Z-values for total cost in groups 1-3 was 12.69, 15.73, and 11.45, respectively; Z-values for average length of stay were 8.33, 6.73, and 3.69, respectively; all P<0.05), indicating that the DRG-PPS reform was effective in controlling hospitalization costs and length of stay.The inter-group analysis revealed statistically significant differences in total cost, nursing cost, pharmaceutical cost, consumable cost, administrative cost, and length of stay( H-values were 22.49, 41.86, 15.61, 200.56, 14.73 and 10.73, respectively; all P<0.05; ), suggesting that there were statistically significant differences in cost control among different age groups in the same DRG group.Furthermore, analysis of specific cases revealed that differences in medical costs among different age groups resulted from the combined effects of clinical practice standardization(reflected in the significant reduction of unnecessary examinations and medication)and policy interventions such as volume-based procurement excluding the adverse effects of cost containment on the medical quality of elderly patients in the six sample patient groups.No substantial rise was observed in the 31-day readmission rate, indicating that admission splitting was unlikely to have occurred. Conclusions:The implementation of the DRG-PPS contributed to cost efficiency in the sample hospital.By establishing a long-term quality control mechanism focused on DRG groups with significant cost reductions in elderly patients, abnormal cost-control behaviors can be effectively identified, and high-quality development of the hospital can be achieved while ensuring healthcare quality for elderly patients.

Objective·To investigate the longitudinal changes in amygdala and hippocampal subfield volumes before and after transcranial magnetic stimulation(TMS)treatment in patients with major depressive disorder(MDD)and explore their correlation with the antidepressant and anxiolytic efficacy of TMS.Methods·A total of 58 patients diagnosed with MDD at Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,were included in this study between January 2018 and August 2023.Clinical depressive and anxiety symptoms were assessed by using the Hamilton Depression Scale(HAMD),Montgomery-Asberg Depression Rating Scale(MADRS),and Hamilton Anxiety Scale(HAMA)at baseline and post-TMS treatment.Patients underwent a baseline magnetic resonance imaging(MRI)scan followed by TMS treatment targeting the left dorsolateral prefrontal cortex(DLPFC)at a frequency of 10 Hz,totaling 20 sessions.A follow-up MRI scan was conducted on the same day the TMS treatment concluded.Amygdala and hippocampal subfield volumes were segmented and calculated by using FreeSurfer v6.0.0 software.Longitudinal changes in the subfield volumes were analyzed with two-way analysis of variance.Controlling for age,sex,and intracranial volume,partial correlation analysis was conducted between subfield volumes and baseline clinical scores.The association between the rate of volume change in brain regions with significant volume changes and symptom improvement(reduction in HAMD,MADRS,and HAMA scores)was evaluated.Results·Following TMS treatment,a significant increase in the volume of the right amygdala central nucleus was observed(t=-2.441,P=0.018).While the volumes of bilateral hippocampal fimbria decreased,the volumes of most hippocampal subfield and the total hippocampus increased(P<0.05).No significant correlations were found between baseline amygdala or hippocampal subfield volumes and clinical depressive and anxiety symptoms.However,only in patients who responded effectively to TMS treatment,a positive correlation was found between the volume change rate of the left hippocampal tail and reductions in anxiety symptoms(HAMA:r=0.334,P=0.044).Conclusion·High-frequency TMS targeting the left DLPFC may induce volume increases in the right amygdala central nucleus and specific hippocampal subfields.Additionally,the volume change rate of the left hippocampal tail is associated with anti-anxiety effects in TMS responders,suggesting that high-frequency TMS targeting the left DLPFC may induce neuroplastic changes in the central nucleus of the right amygdala and key subfields of the hippocampus.

Objective·To investigate the longitudinal changes in amygdala and hippocampal subfield volumes before and after transcranial magnetic stimulation(TMS)treatment in patients with major depressive disorder(MDD)and explore their correlation with the antidepressant and anxiolytic efficacy of TMS.Methods·A total of 58 patients diagnosed with MDD at Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,were included in this study between January 2018 and August 2023.Clinical depressive and anxiety symptoms were assessed by using the Hamilton Depression Scale(HAMD),Montgomery-Asberg Depression Rating Scale(MADRS),and Hamilton Anxiety Scale(HAMA)at baseline and post-TMS treatment.Patients underwent a baseline magnetic resonance imaging(MRI)scan followed by TMS treatment targeting the left dorsolateral prefrontal cortex(DLPFC)at a frequency of 10 Hz,totaling 20 sessions.A follow-up MRI scan was conducted on the same day the TMS treatment concluded.Amygdala and hippocampal subfield volumes were segmented and calculated by using FreeSurfer v6.0.0 software.Longitudinal changes in the subfield volumes were analyzed with two-way analysis of variance.Controlling for age,sex,and intracranial volume,partial correlation analysis was conducted between subfield volumes and baseline clinical scores.The association between the rate of volume change in brain regions with significant volume changes and symptom improvement(reduction in HAMD,MADRS,and HAMA scores)was evaluated.Results·Following TMS treatment,a significant increase in the volume of the right amygdala central nucleus was observed(t=-2.441,P=0.018).While the volumes of bilateral hippocampal fimbria decreased,the volumes of most hippocampal subfield and the total hippocampus increased(P<0.05).No significant correlations were found between baseline amygdala or hippocampal subfield volumes and clinical depressive and anxiety symptoms.However,only in patients who responded effectively to TMS treatment,a positive correlation was found between the volume change rate of the left hippocampal tail and reductions in anxiety symptoms(HAMA:r=0.334,P=0.044).Conclusion·High-frequency TMS targeting the left DLPFC may induce volume increases in the right amygdala central nucleus and specific hippocampal subfields.Additionally,the volume change rate of the left hippocampal tail is associated with anti-anxiety effects in TMS responders,suggesting that high-frequency TMS targeting the left DLPFC may induce neuroplastic changes in the central nucleus of the right amygdala and key subfields of the hippocampus.