Antibody-drug conjugate (ADC), a novel class of antineoplastic agents, combines tumor-specific targeting with potent cytotoxic activity. In recent years, ADC has achieved notable advances in the treatment of non-small cell lung cancer (NSCLC), particularly within therapeutic sequencing after failure of first-line therapy or the emergence of resistance. This paper will systematically review the efficacy and safety evidence of representative ADC in NSCLC, and further to discuss progress and challenges in ADC structural optimization, toxicity management, biomarker identification, and combination strategies, aiming to provide a comprehensive theoretical foundation and practical reference for clinical practice and future research.
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Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Immunoconjugates/chemistry* ; Lung Neoplasms/drug therapy* ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/chemistry*

Objective To investigate the potential core target and its mechanism of Simiao San(SMS)in the treatment of rheumatoid arthritis(RA)using network pharmacology and animal experiments.Methods Active components and corresponding SMS targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and cross-referenced with the Universal Protein(UniProt)database.RA-related targets were screened from The Human Gene Database(GeneCards),Online Mendelian Inheritance in Man(OMIM),Therapeutic Target Database(TTD),DrugBank,and Disease Gene Network(DisGeNet).Protein-protein interaction(PPI)networks were constructed for shared targets between SMS and RA using Search Tool for the Retrieval of Interacting Genes/Proteins(STRING),followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses via The Database for Annotation,Visualization and Integrated Discovery(DAVID).A"herb active component-disease target-signaling pathway"network was established to predict the mechanism of SMS in RA treatment.Molecular docking was performed between aryl hydrocarbon receptor(AHR)and the core active components of SMS to identify AHR-targeting constituents.For animal experiments,30 female SPF-grade C57/BL mice were randomly divided into normal,model,methotrexate(1.52 mg/kg,every 3 days),and SMS(12.48 g/kg,daily)groups with a 30-day intervention.Ankle diameter and arthritis index scores were measured.HE staining was used to assess joint inflammation,whereas immunohistochemistry(IHC)was used to measure cytochrome P450 1A1(CYP1A1),nuclear factor kappa B subunit p65(p65),and phosphorylated p65(p-p65)protein expression levels.Multiplex immunofluorescence(mIHC)was used to evaluate forkhead box protein P3(FOXP3)and interleukin-17A(IL-17A)protein expression.Results Forty-one active components and 228 targets of SMS were identified from TCMSP,whereas 1,207 RA-related targets were extracted from GeneCards,OMIM,TTD,DrugBank,and DisGeNet.Ninety-four overlapping targets were analyzed,yielding 612 GO terms and 143 KEGG pathways.Molecular docking of the ligand-binding domain of AHR with the top 10 Degree values of compounds of SMS(quercetin,stigmasterol,wogonin,beta-sitosterol,kaempferol,baicalein,et al.)revealed that stigmasterol,beta-sitosterol,(S)-canadine,and isocorypalmine was able to bind to AHR stably.In vivo,compared to the model group,the mice of the SMS and methotrexate groups joint swelling and arthritis index scores reduced(P<0.01).IHC indicated elevated CYP1A1 protein and decreased p65 and p-p65 protein levels in the SMS and methotrexate groups(P<0.05,P<0.01).mIHC demonstrated reduced IL-17A and increased FOXP3 protein expression in the SMS and methotrexate groups(P<0.05,P<0.01).Conclusion SMS alleviates joint inflammation in RA mice,potentially by targeting AHR,one of the core targets.SMS may suppress excessive inflammatory responses by activating AHR and inhibiting p65 phosphorylation.Additionally,SMS modulates the helper T cells 17/regulatory T cells balance by downregulating IL-17A and upregulating FOXP3.These results suggest that AHR is a key mediator in T-cell immune regulation.

OBJECTIVE: This study investigates the efficacy and mechanisms of Qingjie Fuzheng Granules (QFG) in inhibiting colitis-associated colorectal cancer (CAC) development via RNA sequencing (RNA-seq) and 16S ribosomal RNA (rRNA) correlation analysis. METHODS: CAC was induced in BALB/c mice using azoxymethane (AOM) and dextran sulfate sodium (DSS), and QFG was administered orally to the treatment group. The effects of QFG on CAC were evaluated using disease index, histology, and serum T-cell ratios. RNA-seq and 16S rRNA analysis assessed the transcriptome and microbiome change. Key pharmacodynamic pathways were identified by integrating these data and confirmed via Western blotting and immunofluorescence. The link between microbiota and CAC-related markers was explored using linear discriminant analysis effect size and Spearman correlation analysis. RESULTS: Long-term treatment with QFG prevented AOM/DSS-induced CAC formation, reduced levels of interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), IL-6, and interferon γ (IFN-γ), and increased CD3⁺ and CD4⁺/CD8⁺ T cells ratio, without causing hepatic or renal toxicity. A 16S rRNA analysis revealed that QFG rebalanced the Firmicutes/Bacteroidetes ratio and mitigated AOM/DSS-induced microbiota disturbances. Transcriptomics and Western blotting analysis identified the nucleotide-binding oligomerization domain-containing protein 2 (NOD2)/nuclear factor kappa-B (NF-κB) pathway as key for QFG's treatment against CAC. Furthermore, QFG decreased the abundance of Bacilli, Bacillales, Staphylococcaceae, Staphylococcus, Lactobacillales, Aerococcus, Alloprevotella, and Akkermansia, while increasing Clostridiales, Lachnospiraceae, Lachnospiraceae_NK4A136_group, Ruminococcaceae, and Muribaculaceae, which were highly correlated with CAC-related markers or NOD2/NF-κB pathway. CONCLUSION By mapping the relationships between CAC, immune responses, microbiota, and key pathways, this study clarifies the mechanism of QFG in inhibiting CAC, highlighting its potential for clinical use as preventive therapy.

Neurodegenerative disorders (NDDs) are prevalent chronic conditions characterized by progressive synaptic loss and pathological protein alterations. Increasing evidence suggested that mitochondrial quality control (MQC) serves as the key cellular process responsible for clearing misfolded proteins and impaired mitochondria. Herein, we provided a comprehensive analysis of the mechanisms through which MQC mediates the onset and progression of NDDs, emphasizing mitochondrial dynamic stability, the clearance of damaged mitochondria, and the generation of new mitochondria. In addition, traditional Chinese medicines (TCMs) and their active monomers targeting MQC in NDD treatment have been demonstrated. Consequently, we compiled the TCMs that show great potential in the treatment of NDDs by targeting MQC, aiming to offer novel insights and a scientific foundation for the use of MQC stabilizers in NDD prevention and treatment.

In order to explore the relationship between ubiquitin proteasome system(UPS)and au-tophagy after macrophage was infected with Brucella.On the one hand,the levels of LC3 Ⅱ、P62 and 20S proteasomes in cell supernatant and peritoneal fluid were determined respectively after RAW264.7 cells were infected and BALB/c mice were intraperitoneal inoculated with Brucella suis(B.suis).The results displayed that UPS was activated firstly,followed by autophagy after B.suis infection.On the other hand,we prepared the UPS-inhibited-cells and ALP-inhibited-cells by lacta-cystin and 3-methy ladenine(3-MA),and then the cells were infected by B.suis and the levels of LC3 Ⅱ、P62 与 20S proteasomes in cell supernatant were determined.The results showed that the ALP function was significantly improved when the effect of M

Objective To investigate the value of cranial CT cisternal grading combined with D-dimer(D-D)and Glasgow Coma Scale(GCS)score in predicting the short-term postoperative prog-nosis of patients with severe traumatic brain injury.Methods A total of 165 patients with severe trau-matic brain injury who were treated in the hospital from January 2019 to May 2024 were selected as study subjects,all underwent craniotomy surgery.Postoperative follow-up was conducted for 3 months to analyze the differences in clinical data and preoperative indicators such as cranial CT cisternal grad-ing,D-D levels,and GCS scores between patients with poor and good prognosis.The value of cranial CT cisternal grading,D-D levels,and GCS scores in predicting short-term postoperative poor prognosis in patients with severe traumatic brain injury was also analyzed.Results Compared with patients with good prognosis,patients with poor prognosis had higher proportion of age,cranial CT cisternal grading of Ⅰ to Ⅱ,D-D levels,and GCS scores＜6(P＜0.05).There were no statistically significant differences in C-reactive protein,prothrombin time,activated partial thromboplastin time,international normalized ratio,total cholesterol,triglycerides,high-density lipoprotein cholesterol,and low-density lipoprotein cholesterol levels between patients with poor and good prognosis(P＞0.05).Cranial CT cisternal grading,D-D levels,and GCS scores were influencing factors for short-term postoperative poor prognosis in patients with severe traumatic brain injury(P＜0.05).The area under the curve for poor prognosis by three indicators in combination was 0.941(95％CI,0.906 to 0.975),which was higher than the area under the curve for the individual predictions of cranial CT cisternal grad-ing,D-D levels,and GCS scores(P＜0.05).Conclusion The influencing factors for short-term postoperative prognosis in patients with severe traumatic brain injury include cranial CT cisternal grading,D-D levels,and GCS scores.The model based on these three indicators has certain appli-cation value in predicting patient prognosis.

By aggregating the essence of theories related with depressive syndrome from historical medical practitioners and based on the extensive clinical experience,traditional Chinese medicine(TCM)master Lin Yi proposed the theory of six-stagnation-based breast disease prevention and treatment.She pointed out that the occurrence of breast diseases is related to six stagnations(qi stagnancy,blood stagnancy,phlegm stagnancy,dampness stagnancy,food stagnancy,and fire stagnancy),and the treatment for breast diseases should start from the six stagnations.The development and progression of breast cancer is closely associated with the imbalance of internal environment and the formation of six stagnations,and breast cancer is one of the major diseases suitable for the TCM syndrome differentiation and treatment.For the treatment of early breast cancer,Professor Lin Yi proposed to divide early breast cancer into four stages,namely perioperative period,peri-chemotherapy period,peri-radiotherapy period,and consolidation period.Guided by the theory of six-stagnation-based breast disease prevention and treatment,therapies of soothing the liver,resolving phlegm,removing stasis,clearing heat,eliminating dampness,promoting digestion,fortifying the spleen,and tonifying the kidney are employed to harmonize the internal environment and alleviate symptoms.The theory of six-stagnation-based breast disease prevention and treatment enriches the TCM theory for the prevention and treatment of breast cancer,refines the principles and methods for the staging and syndrome differentiation of early breast cancer,and holds significant implications for enhancing the efficacy of integrated TCM and western medicine in managing early breast cancer.

Neurodegenerative disorders(NDDs)are prevalent chronic conditions characterized by progressive synaptic loss and pathological protein alterations.Increasing evidence suggested that mitochondrial quality control(MQC)serves as the key cellular process responsible for clearing misfolded proteins and impaired mitochondria.Herein,we provided a comprehensive analysis of the mechanisms through which MQC mediates the onset and progression of NDDs,emphasizing mitochondrial dynamic stability,the clearance of damaged mitochondria,and the generation of new mitochondria.In addition,traditional Chinese medicines(TCMs)and their active monomers targeting MQC in NDD treatment have been demonstrated.Consequently,we compiled the TCMs that show great potential in the treatment of NDDs by targeting MQC,aiming to offer novel insights and a scientific foundation for the use of MQC stabilizers in NDD prevention and treatment.

Objective:To establish a rapid detection method based on matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS)for drug resistance of Carbapenem-resistant Enterobacteriaceae(CRE),so as to provide basis for enhancing clinically diagnostic effect.Methods:A total of 120 suspected CRE strains that were isolated from the clinical laboratory of Jiading District Central Hospital Affiliated to Shanghai University of Medicine&Health Sciences during October 2023 and September 2024 were collected,and the experimental detection of 44 strains was finally completed.The 44 suspected CRE bacterial strains were all from hospitalized patients.A rapid detection protocol based on the MALDI-TOF MS platform was initially established and improved,and experimental detection was carried out using the fully automatic rapid microbial mass spectrometry detection system(VITEK MS).The results of identification review and antimicrobial susceptibility test(AST)for VitEK-2 Compact strain was used as the reference standard.The screening results and detection efficacy of two kinds of detection methods were compared.Results:In the 44 suspected CRE strains,31 CRE strains were screened out by MALDI-TOF MS detection,and 31 CRE stains were screened out by VITEK-2 Compact recheck detection.In them,one strain of Enterobacter cloacae was confirmed as negativity by the MALDI-TOF MS test,but it was confirmed as CRE by the VITEK-2 Compact test.One strain of Klebsiella pneumoniae was confirmed as positivity by the MALDI-TOF MS test,but it was confirmed as mediator for carbapenem drugs by the VITEK-2 Compact test.The tested results of VITEK-2 Compact was used as standard,the results of four-grid table(2×2 contingency table)statistical method indicated that the sensitivity,specificity,accuracy rate and Youden index(R)of MALDI-TOF MS were respectively 96.7%,92.3%,100%and 89.1%.Conclusion:The rapid detection method based on the MALDI-TOF MS platform for CRE drug resistance has simple operation process and high accuracy rate,which can provide a basis for the application of targeted antibacterial drugs at early stage.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.