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.

Aim To explore the possible regulatory effect of leptin on acyl-CoA synthetase long chain fami-ly member ACSL5 and their effect on migration and in-vasion of breast cancer cell,and to explore the underly-ing mechanism.Methods The expression of leptin receptor was detected by immunofluorescence assay.The migration and invasion ability of MCF-7 cells were detected by wound healing assay and Transwell assay respectively.The downstream target gene of leptin was analyzed by PCR microarray data.The expression of ACSL5 in breast cancer and its correlation with the staging and prognosis of breast cancer patients were as-sessed uing bioinformatics methods.The expression of ACSL5 in MCF-7 cells treated with different concentra-tions of leptin was detected using real time fluorescence quantitative polymerase chain reaction(RT-qPCR).Overexpressing ACSL5 was constructed by lentiviral transfection;the expressions of EMT related proteins,AMPK-α and p-AMPK-α were detected by Western blot.Results Leptin promoted breast cancer cell mi-gration and invasion and EMT.ACSL5 was significant-ly low expressed in breast cancer and related to progno-sis.Leptin downregulated the expression of ACSL5 through OBR.Leptin activated AMPK pathway to downregulate ACSL5 and promote migration,invasion and EMT of breast cancer cells.Conclusions Leptin may promote the migration,invasion and EMT of breast cancer by downregulating ACSL5 through activating AMPK pathway.

Objective To investigate the characteristics of a novel FANCL mutation identified in a patient with premature ovarian insufficiency(POI)and to explore its potential functional impacts in vitro.Methods A novel FANCL heterozygous mutation c.1033G>A(p.Glu345Lys)was screened in a patient with POI using whole exome sequencing(WES),which was found to be inherited from a mother who had undergone early menopause.The authenticity of the mutation was identified by Sanger sequencing and the conserved nature of the mutation site was predicted by software.Overexpressing FANCL mutant and wildtype plasmids were constructed and transiently transfected into HEK293T cell lines,and the effect of the mutation was detected by qPCR,immunofluorescence and Western blot.Results The mutation site of FANCL was located within the Ring domain of FANCL,which was highly conserved across multiple species.The mutant showed no significant change in mRNA expression level,while the protein expression level was significantly down-regulated.In vitro cellular experiments further revealed that the mutation leads to decreased expression levels by reducing protein stability.Conclusion A FANCL c.1033G>A mutation was found and it may cause disease in the POI patient due to decreased protein stability.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Aim To investigate the effects of rosavin on hepatocellular steatosis and its mechanism of action.Methods AML-12 and HepG2 cells were induced to undergo hepatocellular steatosis by free fatty acids(FFA),and the optimal inducing concentration was determined by oil red O staining and CCK-8 assay.The cell activity was detected by CCK-8 assay after ro-savin treatment,and the lipid droplet accumulation was observed by oil red O staining.The levels of triglycer-ide(TG),total cholesterol(TC),glutamic oxalacetic transaminase(AST),glutamic pyruvic transaminase(ALT),superoxide dismutase(SOD),glutathione per-oxidase(GSH-Px),and malondialdehyde(MDA)were detected by kits.The potential targets of rosavin in non-alcoholic fatty liver disease(NAFLD)were ana-lyzedby network pharmacology and molecular docking,and the expression of core candidate targets before and after the rosavin intervention was detected by real-time fluorescence quantitative PCR.Results Hepatocyte steatosis was induced by FFA,and the intervention of rosavin(25,50 μmol·L-1)reduced the number of intracellular lipid droplets in hepatocytes in a dose-de-pendent manner,also lowered the cellular levels of TG,TC,AST,ALT,elevated the levels of SOD and GSH-Px,and reduced the levels of MDA.Network pharma-cological analysis and molecular docking yielded five core candidate targets:NOS3,MAPK14,PPARG,TNF-α,and IGF-1,and real-time fluorescence quantitative PCR showed that the action of loxavir significantly re-duced the gene expression of TNF-α and PPARG in hepatocytes after FFA induction.Conclusions Rosa-vin can attenuate the inflammatory response,oxidative stress level,and lipid accumulation in hepatocytes by modulating TNF-α and PPARG,thereby ameliorating FFA-induced hepatocellular steatosis.

Cardiovascular disease is one of the most common causes of death in the world,and related western drugs usually have obvious side effects.Traditional Chinese medicine,characterized by its multi-component and multi-target,has unique advantage in the prevention and treatment of cardiovascular diseases.Cornus Officinal is a histor-ically used plants with medicinal and edible properties.Ancient books and modern literatures have shown that Cor-nus Officinal has the potential to prevent and treat cardiovascular diseases.With the in-depth study of the chemical composition and pharmacological effect of Cornus Officinal,its pharmacodynamic substances and mechanism in the prevention and treatment of cardiovascular diseases are gradually clear.This article reviews the pathways and targets of Cornus Officinal in the prevention and treatment of cardiovascular diseases in recent years,and summarizes its potential effective components,in order to provide theoretical support for the clinical application and traditional Chinese medicine development.

Objective To observe the association between afterschool physical exercise and sleep quality among preschool children,and to explore the proper afterschool physical exercise model for better sleep quality.Methods A cross-sectional study was conducted.From Apr to Jun 2024,a total of 1 430 children from three public kindergartens in Minhang district were enrolled to participate in the survey.Parents were invited to complete the basic sociodemographic information,afterschool physical exercise information and the Children's Sleep Habits Questionnaire.One-way ANOVA and linear mixed effects models were used to explore the relationship between afterschool exercise and sleep quality.Results A total of 1 430 questionnaires were sent out and 1 384 were recovered with a recovery rate of 96.78%.Among them 1 366 were valid,with an effective rate of 95.52%.The average age of the children was(5.19±0.87)years old with gender ration of 1.07∶1(male:female).The prevalence of poor sleep quality was 80.60%(regarding a CSHQ total score>41 as cutoff).A one-way ANOVA indicated that time on afterschool physical exercise was significantly associated with sleep duration,Night waking,and sleep onset delay(P<0.05).After adjusting for age,gender,the only child or not,main caregiver,and parental education and occupation,linear mixed effects models showed that engaging in afterschool physical activity for at least 180 mins per week has a statistically significant predictive effect on sleep duration scores(β=-0.50,z=-4.52,95%CI:-0.72,-0.28,P<0.001),night waking scores(β=-0.16,z=-2.34,95%CI:-0.29,-0.02,P=0.020),and sleep onset delay scores(β=-0.14,z=-2.35,95%CI:-0.26,-0.02,P=0.019).Conclusion Afterschool exercise was significantly associated with sleep quality among preschool children in Minhang district of Shanghai.The time≥180 min on afterschool exercise per week in preschool children was significantly positively associated with maintaining sleep duration,reducing night wakings and shortening the latency to fall asleep.The habit of afterschool exercise and the time on afterschool exercise should be emphasized by parents and the society to improve sleep quality among preschool children.

Objective:To investigate the protective effect of achyranthes bidentata(AB)on sperm quality in mice with sper-matogenic disorder through the glycolytic metabolic pathway and its action mechanism.Methods:We equally randomized 40 Kun-ming mice into a normal control,a model control,a low-dose AB(3.5 g/kg)and a high-dose AB group(7.0 g/kg),and established the model of spermatogenic disorder in the latter three groups of mice by intraperitoneal injection of doxorubicin(30 mg/kg).Two days after modeling,we collected the testis and kidney tissues and blood samples from the mice for observation of the pathological changes in the testis tissue by HE staining,detection of perm motility with the sperm quality analyzer,examination of the apoptosis of testis cells by flow cytometry,measurement of the levels of testosterone(T),malondialdehyde(MDA),superoxide dismutase(SOD)and cata-lase(CAT)in the serum and testis tissue by ELISA,and determination of expressions of the key enzymes of glycolysis hexokinase Ⅱ(HK2),pyruvate kinase M2(PKM2),platelet phosphofructokinase(PFKP),lactate dehydrogenase A(LDHA)and the meiosis pro-teins REC8 and SCP3 by Western blot,and the mRNA expressions of glycolytic phosphofructokinase 1(PFK1),phosphoglycerate ki-nase 1(PGK1),tumor necrosis factor-α(TNF-α)and interleukin-1 β(IL-1β)by fluorescence quantitative PCR(FQ-PCR).Results:Compared with the model controls,the mice in the AB groups showed significant increases in the testis coefficient,kidney in-dex,sperm concentration,sperm motility,spermatogonia,primary spermatocytes,spermatids,sperm count and the serum T level(P＜0.05 orP＜0.01),but dramatic decreases in the apoptosis of testis cells and percentage of morphologically abnormal sperm(P＜0.01).Achyranthes bidentata also significantly elevated the levels of SOD and CAT,and down-regulated the mRNA expressions of MDA,TNF-α and IL-1β(P＜0.05 or P＜0.01),and up-regulated the protein expressions of HK2,PKM2,PFKP,LDHA,REC8 and SCP3,and expressions of the glycolysis key genes Pfk1 and Pgk1(P＜0.05 orP＜0.01).Conclusion:Achyranthes bidentata ameliorates doxorubicin-induced spermatogenic disorder in mice by regulating the glycolytic pathway and reducing oxidative stress and the expressions of inflammatory factors.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.