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.

OBJECTIVES: To explore the predictive factors for hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants and to construct a nomogram prediction model for hsPDA occurrence in this population. METHODS: A retrospective analysis was conducted on the clinical data of preterm infants with gestational age <32 weeks diagnosed with patent ductus arteriosus (PDA) who were delivered at Nanjing Women and Children's Healthcare Hospital from January 2020 to December 2022. The subjects were divided into an hsPDA group (52 cases) and a non-hsPDA group (176 cases) based on the presence of hsPDA. Univariate analysis and multivariate logistic regression analysis were performed to screen predictive variables regarding the general information of the infants at birth, maternal pregnancy and delivery conditions, and relevant indicators during hospitalization. A nomogram prediction model for hsPDA occurrence was constructed using R software in preterm infants. Internal validation was performed using the Bootstrap method. Finally, the predictive model was evaluated for calibration, discrimination ability, and clinical utility. RESULTS: Multivariate regression analysis showed that the ratio of the left atrium to aorta diameter (LA/AO), mode of delivery (vaginal), and duration of mechanical ventilation were independent predictive factors for hsPDA in preterm infants (P<0.05). Based on the results of univariate analysis and multivariate logistic regression analysis, variables used to construct the nomogram prediction model for hsPDA risk included: LA/AO ratio, mode of delivery (vaginal), duration of mechanical ventilation, 5-minute Apgar score, and the presence of neonatal respiratory distress syndrome requiring surfactant therapy. The area under the receiver operating characteristic curve for this model was 0.876 (95%CI: 0.824-0.927), and the calibrated curve was close to the ideal reference line, indicating good calibration. The Hosmer-Lemeshow test demonstrated that the model fit well, and the clinical decision curve was above the extreme curves. CONCLUSIONS The nomogram prediction model, constructed using five variables (LA/AO ratio, vaginal delivery, duration of mechanical ventilation, 5-minute Apgar score, and the presence of neonatal respiratory distress syndrome requiring surfactant therapy), has reference significance for predicting the occurrence of hsPDA in preterm infants and provides valuable guidance for the early clinical identification of hsPDA.
Humans ; Ductus Arteriosus, Patent/etiology* ; Nomograms ; Female ; Infant, Newborn ; Infant, Premature ; Retrospective Studies ; Male ; Hemodynamics ; Logistic Models ; Pregnancy

OBJECTIVE: Coronavirus disease 2019 (COVID-19) can result in fatigue and post-exertional malaise; however, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exacerbates lower urinary tract symptoms (LUTS) is unclear. This study investigated the association between prenatal SARS-CoV-2 infection and postpartum LUTS. METHODS: A multicenter, retrospective cohort study was conducted at two tertiary hospitals in China from November 1, 2022, to November 1, 2023. Participants were classified into infected and uninfected groups based on SARS-CoV-2 antigen results. LUTS prevalence and severity were assessed using self-reported symptoms and the Incontinence Impact Questionnaire-Short Form (IIQ-7). Pelvic floor muscle activity was measured using electromyography following the Glazer protocol. Group comparisons were performed to evaluate the association of SARS-CoV-2 infection with LUTS and electromyography parameters, with stratified analyses conducted using SPSS version 26.0. RESULTS: Among 3,652 participants (681 infected, 2,971 uninfected), no significant differences in LUTS prevalence or IIQ-7 scores were observed. However, SARS-CoV-2 infection was an independent factor influencing the electromyographic activity of the pelvic floor muscles (mean tonic contraction amplitudes), regardless of delivery mode ( P = 0.001). CONCLUSION Prenatal SARS-CoV-2 infection was not significantly associated with an increased risk of postpartum LUTS but independently altered pelvic floor muscle electromyographic activity, suggesting potential neuromuscular effects.
Humans ; Female ; COVID-19/epidemiology* ; Retrospective Studies ; Adult ; Pregnancy ; Lower Urinary Tract Symptoms/virology* ; Postpartum Period ; Pregnancy Complications, Infectious/virology* ; China/epidemiology* ; Electromyography ; SARS-CoV-2/physiology* ; Pelvic Floor/physiopathology* ; Prevalence

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.

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.

Objective:To investigate the expression and physiological significance of the ferroptosis marker 4-hydroxynonenal(4-HNE)in myofibroblasts induced by transforming growth factor-β1(TGF-β1),providing theoretical evidence for its potential role in the diagnosis and treatment of fibrosis in sys-temic sclerosis(SSc).Methods:Mouse embryonic fibroblasts(NIH3t3)were cultured and divided into two groups after 12 h of starvation:the control group(cultured in 1％serum-containing medium)and the TGF-β1 group(cultured in 10 μg/L TGF-β1 with 1％serum-containing medium).Cell morphology changes in both groups were observed under a microscope.To confirm successful establishment of the SSc cell model,fibrosis markers were analyzed using reverse transcription quantitative real-time PCR(RT-qPCR)and Western blot.Next,flow cytometry was employed to assess the intracellular levels of reactive oxygen species(ROS)in both groups.Finally,Western blot and immunofluorescence staining were used to measure the expression of 4-HNE in the TGF-β1-treated cells.Results:Microscopic observations re-vealed that TGF-β1 treatment caused the NIH3t3 cells to transition from a typical spindle shape to a flat,polygonal shape with multiple protrusions,indicating fibroblast activation.The RT-qPCR and Western blot analyses showed that the expression of the fibrosis marker Vimentin was significantly upregulated in the TGF-β1 group compared with the control group(P＜0.01),confirming that TGF-β1 effectively pro-moted fibrosis-related gene and protein expression.Flow cytometry results indicated that TGF-β1 signifi-cantly elevated intracellular ROS levels,suggesting the induction of oxidative stress.Furthermore,both Western blot and immuno-fluorescence staining demonstrated a significant increase in 4-HNE expression in the TGF-β1-treated cells(immunofluorescence intensity P＜0.05).Conclusion:TGF-β1 promotes fibroblast activation and fibrosis while inducing ROS production,leading to a marked increase in 4-HNE expression.Given the role of 4-HNE as a marker of lipid peroxidation and its elevated levels in the SSc cell model,this study suggests that 4-HNE could serve as a potential biomarker for fibrosis in SSc.The findings highlight the importance of investigating the mechanisms of 4-HNE in fibrosis and suggest that targeting this pathway could offer new therapeutic opportunities for treating SSc.

Abstract: Objective To analyze the antimicrobial resistance rate and risk factors of multi drug resistant organisms (MDRO) in bloodstream infection for rational treatment. Methods　A total of 696 cases of bloodstream infections of Staphylococcus aureus, Enterococcus, Enterobacteriaceae (excluding Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter in our hospital from 2017 to 2021 were selected, and 711 pathogenic strains were isolated from their whole blood samples. The antimicrobial resistance rates of various multi drug resistant strains were analyzed and the risk factors of MDRO infection were analyzed. Results　696 non repeated cases were screened out from 13 187 whole blood culture specimens, with a positive rate of 5.3%, and a total of 711 blood influenza pathogens were detected, among them, 350 strains of MDRO were detected with a detection rate of 49.23% (350/711). Among the pathogenic bacteria of bloodstream infection, Escherichia coli was the most, with 277 strains accounting for 38.96% (277/711), of which 201 strains were MDRO, accounting for 57.43% (201/350); followed by Klebsiella pneumoniae and Staphylococcus aureus, with 155 strains accounting for 21.80% (155/711) and 89 strains accounting for 12.52% (89/711), among which 43 strains of Klebsiella pneumoniae MDRO accounted for 12.29% (43/350) and 38 strains of Staphylococcus aureus MDRO accounted for 10.86% (38/350). The change trend of the three pathogens during 2017-2021 was not obvious. The drug sensitivity test showed that Escherichia coli and Klebsiella pneumoniae were highly resistant to cephalosporins and fluoroquinolones, and the drug resistance rate of aminoglycosides was relatively low. They had almost no resistance to cephalosporins and carbapenems. Staphylococcus aureus has a high resistance rate to lincomycin and macrolides, but no resistance to oxazolidinone, glycopeptides and glycylcyclins. There were 350 cases of MDRO infection and 361 cases of non MDRO infection. Univariate analysis showed that the age, sex, cardiovascular and cerebrovascular history, renal insufficiency, lung disease, hypoalbuminemia, hepatobiliary disease, electrolyte disorder and anemia of the patients had no statistical significance in MDRO infection (P>0.05); diabetes, urinary tract infection, surgical operation and burn were the influencing factors of MDRO (P<0.05). According to logistic analysis, diabetes, urinary tract infection, surgical operation and burn were the risk factors of MDRO infection (P<0.05). Conclusion　The infection of MDRO in patients with bloodstream infection is serious, and early prevention and control should be paid attention to, and the principle of graded use of antibiotics should be strictly observed, and the rational application should be carried out to actively and effectively control the production of MDRO.

[Abstract] Objective To explore the effect of serine protease inhibitor Kazal-type 1(SPINK1) on the proliferation of hepatocellular carcinoma cells RH-35 and its underling molecular mechanism. Methods Spink1 gene expression in liver cancer and rat liver cancer models were analyzed by Gene Expression Omnibus (GEO) data, RH-35 cells were treated with rrSPINK1 protein, the effect of rrSPINK1 on the proliferation and apoptosis of RH-35 cells was explored by MTT, 2’-deoxy-5-ethynyluridine(EdU) and flow cytometry, the molecular mechanism of SPINK1 regulating liver cancer were detected by Real-time PCR and Western blotting. Results The results showed that Spink1 gene was over-expressed significantly in liver cancer and rat liver cancer models, rrSPINK1-treated RH-35 cells showed increased viability, EdUpositive cell rate, and the proportion of cells in S phase and G

Objective To explore the role pathway and pattern of the transcription factor myeloma cancer gene (MYC) and its mRNA interaction with microRNA(miRNA, miR) and ciccular RNA(circRNAs) at 0 hour and 6 hour in the rat liver regeneration. Methods The rat 2/3 hepatectomy (partial hepatectomy，PH) model was prepared as described by Higgins, the expression changes of mRNA, miRNA and circRNA together named as competing endogenous RNAs(ceRNA) of remnant liver were detected by the large-scale quantitative detection technology, the interaction network of ceRNA was constructed by Cytoscape 3.2 software, and their correlation in expression and role were analyzed by ceRNA comprehensive analysis. Results It was found that at 0 hour and 6 hours after PH, the ratio value of MYC mRNA showed 0.15±0.03 and 2.36±0.20, miR-540-3p displays 3.00±0.43 and 0.79±0.01, circRNA_04996 showed 1.43±0.43 and 3.14±0.94. At the same time, the four kinds of inflammatory reaction-related genes plasminogen activator urokinase receptor (PLAUR), tumor necrosis factor (TNF), interleukin 1 receptor type 2 (IL1R2), ect, which were prometed in expression by MYC, were down-regulated at 0 hour after PH, but the inflammatory reaction-related genes natriuretic peptide A (NPPA), nuclear receptor subfamily O group B member 2 (NROB2) and peroxisome proliferator activated receptor alpha (PPARA), which were inhibited in expression by MYC, were up-regulated at 0 hour after PH. On the other hand, the three kinds of inflammatory reaction-related genes PLAUR, TNF, IL1R2, ect, which are prometed in expression by MYC, were up-regulated at 6 hours after PH, but the inflammatory reaction-related genes NPPA, NROB2 and PPARA, which were inhibited in expression by MYC, were down-regulated at 6 hours after PH. Conclusion The correlation in expression and role of the miRNA, which are inhibited by circRNAs, MYC, its mRNA is inhibited by miRNAs, and the inflammatory reaction-related genes, which are regulated by MYC, and are helpful for the hepatocyte to be in non-inflammatory reaction state at 0 hour after PH and to be in inflammatory reaction state at 6 hours after PH.

This study aimed to explore the anti-depressant components of Rehmanniae Radix and its action mechanism based on network pharmacology combined with molecular docking. The main components of Rehmanniae Radix were identified by ultra-high performance liquid chromatography-quadrupole/Orbitrap high resolution mass spectrometry(UPLC-Q-Orbitrap HRMS), and the related targets were predicted using SwissTargetPrediction. Following the collection of depression-related targets from GeneCards, OMIM and TTD, a protein-protein interaction(PPI) network was constructed using STRING. GO and KEGG pathway enrichment analysis was performed by Metascape. Cytoscape 3.7.2 was used to construct the networks of "components-targets-disease" and "components-targets-pathways", based on which the key targets and their corresponding components were obtained and then preliminarily verified by molecular docking. Rehmanniae Radix contained 85 components including iridoids, ionones, and phenylethanoid glycosides. The results of network analysis showed that the main anti-depressant components of Rehmanniae Radix were catalpol, melittoside, genameside C, gardoside, 6-O-p-coumaroyl ajugol, genipin-1-gentiobioside, jiocarotenoside A1, neo-rehmannioside, rehmannioside C, jionoside C, jionoside D, verbascoside, rehmannioside, cistanoside F, and leucosceptoside A, corresponding to the following 16 core anti-depression targets: AKT1, ALB, IL6, APP, MAPK1, CXCL8, VEGFA, TNF, HSP90 AA1, SIRT1, CNR1, CTNNB1, OPRM1, DRD2, ESR1, and SLC6 A4. As revealed by molecular docking, hydrogen bonding and hydrophobicity might be the main action forms. The key anti-depression targets of Rehmanniae Radix were concentrated in 24 signaling pathways, including neuroactive ligand-receptor interaction, neurodegenerative disease-multiple diseases pathway, phosphatidylinositol 3-kinase/protein kinase B pathway, serotonergic synapse, and Alzheimer's disease.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Molecular Docking Simulation ; Network Pharmacology ; Neurodegenerative Diseases ; Plant Extracts ; Rehmannia