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.

Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

Objective To analyze the epidemiological characteristics of poisonous mushroom-related foodborne disease incidents in Chongqing from 2010 to 2024, and to provide a scientific basis for effective prevention and control of mushroom-related foodborne diseases. Methods Data of poisonous mushroom related foodborne disease incidents reported by the CDCs of 39 districts and counties in Chongqing from 2010 to 2024 were collected, and their epidemic characteristics were analyzed. Results A total of 264 poisonous mushroom poisoning outbreaks were reported in Chongqing from 2010 to 2024, resulting in 1 046 cases of illness, 543 hospitalizations, and 15 deaths, with a mortality rate of 1.43%. The peak of poisoning incidents was from June to October, accounting for 89.02% of the total number of incidents. The top three high-incidence areas were Pengshui Miao Tujia Autonomous County, Dianjiang County, and Nanchuan District. Poisonous mushroom poisoning incidents occurring in household settings, accidental picking and ingestion, and cases involving unidentified mushroom species accounted for 89.02%, 83.33%, and 90.15% of all foodborne disease outbreak incidents, respectively. Conclusion Foodborne disease incidents related to poisonous mushrooms in Chongqing City show an upward trend, and the effectiveness of prevention and control needs to be improved. Based on their seasonal, regional and household clustering characteristics, efforts should be made before the peak season of mushroom poisoning in high-risk areas, targeting key populations with health education, monitoring and early warning, food safety supervision, and medical treatment.

Objective: To analyze the structural changes in whole blood and apheresis platelet donations in Chinese Society of Blood Transfusion (CSBT) sentinel units from 2021 to 2025, and to provide evidence for donor recruitment and blood service management. Methods: Aggregated data reported by sentinel sites were collected and stratified according to six indicators: age, sex, donation history, donation volume, donation site, and organization mode. Pearson χ test, Cramer′V coefficient, Cochran-Armitage trend test and simple linear regression were adopted for analysis. Results: A total of 16 256 973 whole blood donations and 1 576 546 apheresis platelet donations were included. Among whole-blood donations, the proportion of donors aged 18-22 years decreased from 27.30% to 10.60%. The proportion of male donors increased from 58.81% to 63.13%; the proportion of people aged 30 and above increased from 58.40% to 75.30%; the proportion of fixed locations rose from 28.37% to 36.57%; the proportion of social groups increased from 21.69% to 39.69%. The 400-mL donations decreased from 62.12% to 53.46%, while individually initiated voluntary donations remained above 50%. Apheresis platelet donations were predominantly from males, individuals aged 30-39 years, and repeat donors; 2-treatment-unit apheresis platelet donations increased from 67.19% to 74.93%, and individually initiated donations accounted for 92.97%-96.02%. Statistically significant overall annual compositional differences were observed for all six indicators (all P<0.001), whereas linear trends for some sub-categories were not statistically significant. Conclusion: In the participating CSBT sentinel units, among whole blood donations, the proportions of donors aged 18-22 years, university-organized group donations, and donations at blood mobiles decreased, whereas the proportions of organizational group donations and donations at fixed venues increased. The apheresis platelet donation cohort is relatively mature and is evolving toward a high-efficiency donation model. Individual voluntary donation remains the primary organization mode for both donation types. Strategies such as youth donor recruitment, optimized layout of fixed donation sites, and retention of repeat donors should be strengthened to improve the resilience of blood supply.

Objective To initially explore the possibility of applying the fluorescence micro-optical sectioning tomography(fMOST)high-resolution 3D reconstruction system to the morphological study of the intestinal nervous system and to preliminarily establish a method for studying the morphology of the intestinal nervous system using this system.Methods fMOST high-resolution 3D reconstruction system was used to study the intestinal nervous system of C57BL/6 mice in detail.Based on this method,a new morphological method of the visceral nervous system of small animal models was explored at the single-cell level.Results Compared with the large intestine,the small intestine lacked the typical myenteric plexus(Auerbach),deep mucosal plexus(Henley),and submucosal superficial plexus(Meissner).Conclusion The result of this paper provide a clearer and systematic display of the anatomical structure of the enteric nervous system in C57BL/6 mice,and further clarify the similarities and differences between the enteric nervous system of mice and human,and provide a theoretical basis for its rational application in the study of digestive system diseases.The morphological study of fMOST high-resolution 3D reconstruction system is not limited to the central nervous system,but can be extended to the morphological study of multiple visceral nervous systems.

Objective To explore the risk factors for nocturnal hypoxemia in patients with ob-structive sleep apnea(OSA)and construct an assessment model.Methods A total of 303 patients with OSA diagnosed by polysomnography(PSG)were selected as research objects.Based on PSG re-sults,they were divided into case group(171 patients with hypoxemia)and control group(132 pa-tients without hypoxemia).Materials were compared between the two groups;multivariable Logistic re-gression analysis was used to screen risk factors for nocturnal hypoxemia in OSA patients and construct a risk assessment model.Value of the model was evaluated by the area under the curve(AUC)of the receiver operating characteristic(ROC)curve and K-fold cross-validation.Results The case group had significantly higher values in age,body mass index(BMI),neck circumference,proportion of smokers,hemoglobin,red cell distribution width(RDW),apnea-hypopnea index(AHI),the longest apnea duration(LAD),snoring index,and percentage of apnea-hypopnea duration to total sleep time(AHT％)when compared to the control group(P＜0.05).Logistic regression analysis showed that high BMI,high RDW,long LAD,and high AHT％were risk factors for nocturnal hypoxemia in OSA patients(P＜0.05).AUC value(0.952)of the ROC curve of the assessment model constructed based on these factors was higher than the AUC values of BMI(0.833),RDW(0.780),LAD(0.866),and AHT％(0.898)alone.One hundred times of 10-fold cross-validation demonstrated that the assessment model had good generalization ability.Conclusion Nocturnal hypoxemia in OSA patients is associated with high BMI,high RDW,long LAD,and high AHT％.The model constructed based on these factors plays an important role in evaluating nocturnal hypoxemia in OSA patients.

Objective To explore the application value of a holistic nursing model based on the Delphi method in patients with acute myocardial infarction(AMI).Methods A total of 110 AMI patients treated at Diqing Shangri-La People's Hospital in Yunnan Province from January 2019 to January 2020 were enrolled and divided into a control group and an observation group,with 55 patients in each,based on their admission order.The control group received routine nursing care,while the observation group received holistic nursing model intervention based on Delphi in addition to the routine nursing care.After 6 months of nursing,the left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),general self-efficacy scale(GSES)score,complications,and changes in nursing satisfaction were compared and analyzed between the two groups.Results(1)After nursing,the LVEF significantly increased and the LVEDV and LVESV significantly decreased in both groups;the increase in LVEF was more significant,and the decrease in LVEDV and LVESV was more pronounced in the observation group(P<0.05);(2)The GSES scores of patients in both groups improved compared to before nursing,with a more significant improvement in the observation group(P<0.05);(3)The incidence of adverse events during hospitalization was lower in the observation group than in the control group(P<0.05);(4)The satisfaction rate was higher in the observation group than in the control group after nursing(P<0.05).Conclusion The application of a holistic nursing model based on Delphi in AMI patients can effectively improve cardiac function and self-management efficacy,reduce the incidence of complications,and enhance nursing satisfaction,demonstrating high feasibility.

Objective To investigate the molecular mechanism by which Lichong Xiaozheng Granules(LCXZ)sensitize ovarian cancer to cisplatin(DDP)treatment.Methods LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage.In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts,the effects of daily gavage of distilled water(control group),intraperitoneal injection of DDP(5 mg/kg)once a week,or both DDP injection and daily LCXZK gavage(15 g/kg)on tumor growth were evaluated.Histopathological changes in the xenografts and kidneys were assessed with HE staining.RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis.The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting.Results A total of 218 blood-borne components of LCXZ were detected by LC-MS.In the tumor-bearing mice,treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3%and 72.6%compared with that in the control group,respectively.Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups.Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3(ANT3)with binding energies below-6 kcal/mol.Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice,and these changes were more pronounced in the combined treatment group.The expression levels of BAX,ANT3,cleaved caspase-3 and cleaved caspase-9 were increased,whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups.Conclusion LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.

Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.