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.

Due to the poor ionization efficiency and the weak mass spectrometry(MS)intensity of weakly polar substances,direct analysis using the traditional electrospray ionization mass spectrometry(ESI-MS)is a big challenge.In this study,a novel rapid on-site detection method of four prohibited sex hormones in cosmetics was proposed using online derivatization strategy coupled with a miniature mass spectrometer.The target substances in the samples were extracted by a custom-made polyaniline/multi-walled carbon nanotube solid-phase microextraction(SPME)probe.The stirring speed was 200 r/min,the extraction temperature was 40℃,and the extraction time was 2 min.A pulled dual-channel θ borosilicate glass capillary emitter was used as the nano-ESI ion source.The SPME probe was inserted into the channel containing methanol in theθborosilicate glass capillary.When the spray voltage was applied,the four sex hormones were desorbed and formed spray microdroplets,which then collided with the hydroxylamine microdroplets generated from the other channel.The microdroplets of reaction product entered into the miniature mass spectrometer for direct analysis.The limits of detection(LOD)and limits of quantification(LOQ)for the four sex hormones were 10-20 ng/mL and 20-50 ng/mL,respectively.The recoveries were from 84.6%to 107.8%with the relative standard deviations(RSD)from 4.1%to 11.6%.Compared to detection without derivatization,the MS signals of the four target substances were increased by 3 to 15 times.This method was simple,rapid,highly efficient and sensitive,and suitable for on-site rapid analysis of weakly polar sex hormones in cosmetics.

Objective: This study aimed to explore the correlation between balance function and core muscle activation in patients with adolescent idiopathic scoliosis (AIS), compared to healthy individuals. Methods: A total of 24 AIS patients and 25 healthy controls were recruited. The limits of stability (LOS) test were conducted to assess balance function, while surface electromyography was used to measure the activity of core muscles, including the internal oblique, external oblique, and multifidus. Diaphragm thickness was measured using ultrasound during different postural tasks. Center of pressure (COP) displacement and trunk inclination distance were also recorded during the LOS test. Results: AIS patients showed significantly greater activation of superficial core muscles, such as the internal and external oblique muscles, compared to the control group (p < 0.05). Diaphragm activation was lower in AIS patients during balance tasks (p < 0.01). Although no significant difference was observed in COP displacement between the groups, trunk inclination was significantly greater in the AIS group during certain tasks (p < 0.05). Conclusion These findings suggest distinct postural control patterns in AIS patients, highlighting the importance of targeted interventions to improve balance and core muscle function in this population.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective:By analyzing the correlation between genotypes and phenotypes,we explored the impact of the variant c.917T＞C(p.L306P)in the ABO*B.01 allele on the expression and function of B-glycosyltransferase(GTB).This study aims to elucidate the molecular mechanisms underlying the occurrence of this subtype.Methods:The study subjects included a blood donor specimen with incompatible forward and reverse ABO typing results.ABO phenotyping was determined using ABO blood group serology and GTB activity testing.Subsequently,Sanger sequencing and third-generation sequencing based on the PacBio platform were employed to sequence the ABO gene,resulting in the determination of haplotype sequences.Mutations were identified through sequence alignment.An in vitro cell expression system was established to assess the impact of the mutation site on antigen expression.Results:The index case in this study was identified as B subtype with the allelic genotype c.917T＞C in ABO*B.01/ABO*O.01.01,which has not been previously reported.In vitro expression results revealed decreased levels of GTB expression and overall GTB activity in the mutant cells.Furthermore,the expression of the B antigen on the cell membrane was weaker in the mutant cells compared to the wild-type cells.Conclusion:The p.L306P variation caused by the c.917T＞C mutation in the ABO*B.01 allele may be a genetic factor contributing to the reduced expression of B antigens on the surface of red blood cells.

Objective In this preliminary survey,we sought to determine the composition of mosquito species inhabiting the Emeifeng Nature Reserve,Fujian Province,China.Methods Mosquito larvae were collected by straw and spoon trapping,and adult mosquitoes were collected by lamp trapping at selected breeding sites in the reserve.The specimens were initially identified based on morphology,with subsequent verification using molecular biology methods.Results A total of 34 mosquito species in 13 genera were collected,among which,there were 4 species of Anopheles(Genus Anopheles Meigen,1818),2 species of Lutzia(Genus Lutzia Theobald,1903),15 species of Culex(Genus Culex Linnaeus,1758),4 species of Stegomyia(Genus Stegomyia Theobald,1901),and single species of Hulecoeteomyia(Genus Hulecoeteomyia Theobald,1904),Luius(Genus Luius Reinert,Harbach et Kitching,2008),Aedes(Genus Aedes Meigen,1818),Downsiomyia(Genus Downsiomyia Vargas,1950),Collessius(Genus Collessius Reinert,Harbach et kitching,2006),Uranotaenia(Genus Uranotaenia Lynch 1891),Armigeres(Genus Armigeres Theobald,1901),Toxorhynchites(Genus Toxorhynchites Theobald,1901),and pestle mosquito(Genus Tripteroides Giles,1904).Conclusions The species composition of mosquitoes sampled in the Emeifeng Nature Reserve will provide a basis for further research on mosquito vectors and contribute to measures for local mosquito control.

OBJECTIVE: To retrospectively analyze the characteristics and influencing factors of COVID-19 infection in patients with multiple myeloma (MM) who underwent autologous hematopoietic stem cell transplantation (AHSCT). METHODS: The clinical data of MM patients who underwent AHSCT in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from May 26, 2021 to December 26, 2022 were collected. The onset of COVID-19 infection, corresponding symptoms and laboratory tests were followed up in outpatient or by the means of telephone contact and online questionnaires. Related analysis was then performed. RESULTS: This study included 96 patients, and 72 cases among them were infected with COVID-19 while 24 cases were uninfected. Logistic regression analysis showed that vaccination did not significantly reduce the risk of COVID-19 infection, but patients who received two doses of the vaccine had a lower risk of developing moderate and severe disease than those who did not receive or received one dose (OR =0.06, P =0.029). Patients who received daratumumab before had a higher risk of COVID-19 infection (OR =5.78, P =0.039), while those with a history of immunomodulatory drugs (IMiDs) had the opposite effect (OR =0.31, P =0.028). The use of both drugs did not affect the severity of COVID-19 infection. CONCLUSION For MM patients undergoing AHSCT as first-line chemotherapy, COVID-19 vaccination does not significantly reduce the infection rate, but it plays a role in preventing moderate and severe cases. The application of antineoplastic drugs with different mechanisms has a certain impact on the susceptibility to the COVID-19, which should be considered comprehensively when creating treatment plans.
Humans ; Multiple Myeloma/complications* ; COVID-19/epidemiology* ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Male ; Female ; Middle Aged ; SARS-CoV-2 ; Adult ; Antibodies, Monoclonal

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*