OBJECTIVE To explore the relationship between severe cardiotoxicity caused by oxaliplatin combined with capecitabine and genetic polymorphism， thereby providing references for safe clinical medication use. METHODS Clinical pharmacists conducted a correlation analysis on a case of severe cardiotoxicity in a rectal cancer patient at Qilu Hospital of Shandong University following first-time treatment with standard doses of oxaliplatin combined with capecitabine. Case reports of cardiotoxicity caused by oxaliplatin and capecitabine were retrieved from the Chinese and English databases such as CNKI and PubMed.Basic patient information， drug treatment plan， and cardiotoxic manifestations were extracted and summarized. Combined with the patient’s genetic polymorphism test results related to the metabolism and excretion of platinum-based and fluorouracil drugs， potential mechanisms and prevention strategies for cardiotoxicity induced by oxaliplatin and capecitabine were discussed. RESULTS The patient exhibited homozygous mutations in ABCB1 C3435T and G2677T/A， a heterozygous mutation in MTHFR A1298C， and a heterozygous mutation in GSTP1 A105G， indicating impaired metabolism and excretion of oxaliplatin and capecitabine. The pharmacists recommended discontinuing oxaliplatin and reducing capecitabine to 50% of the original dose for subsequent treatment. The physicians adopted this advice， and the patient experienced no further severe adverse reactions with stable disease progression. CONCLUSIONS Oxaliplatin and capecitabine may cause severe cardiotoxicity. Medical institutions with adequate resources should perform genetic polymorphism test related to drug metabolism and excretion in patients prescribed these agents. For patients with multiple gene mutations， close monitoring and appropriate dose reductions are recommended to ensure medication safety and efficacy.

Patients with metastatic castration-resistant prostate cancer (mCRPC) face poor prognoses due to tumor heterogeneity and drug resistance. Antibody-drug conjugates (ADCs) have been under development for over two decades for mCRPC treatment. Several clinical trials have demonstrated promising antitumor activity and acceptable safety profiles for ADCs in this setting. Among prostate-specific membrane antigen (PSMA)-targeted ADCs, ARX517 demonstrates superior safety and more significant prostate-specific antigen (PSA) reductions compared to earlier agents such as MLN2704, PSMA-ADC, and MEDI3726. ADCs targeting B7-H3, such as MGC018 and DB-1311, have also shown antitumor activity. ADCs targeting other antigens, including six-transmembrane epithelial antigen of the prostate (STEAP)1 (DSTP3086S), trophoblast cell surface antigen (TROP)2 (sacituzumab govitecan), and solute carrier (SLC) 44A4 (ASG-5ME), have shown preliminary antitumor activity in early trials but face challenges with insufficient efficacy or toxicity. Tisotumab vedotin (targeting tissue factor) has shown no significant therapeutic response in mCRPC. Meanwhile, disitamab vedotin (HER2-targeted), ABBV-969 and DXC008 (both dual PSMA/STEAP1-targeted) are currently under evaluation. Notably, an international multicenter phase Ⅲ clinical trial (NCT06925737) for mCRPC has been initiated in May 2025 for evaluating B7-H3-targeted ADC ifinatamab deruxtecan. This review summarizes recent advances in ADCs targeting key antigens in mCRPC (including PSMA, B7-H3, STEAP1, TROP2, SLC44A4, and others) and explores combination strategies, offering insights to inform the clinical management of mCRPC.
Humans ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Male ; Immunoconjugates/therapeutic use* ; Glutamate Carboxypeptidase II/immunology* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; B7 Antigens/immunology* ; Neoplasm Metastasis ; Prostate-Specific Antigen ; Antigens, Neoplasm/immunology* ; Antigens, Surface ; Camptothecin/analogs & derivatives* ; Oxidoreductases

Objective:To investigate the outcomes of endoscopic balloon dilation laryngoplasty （EBDL） in managing acquired subglottic stenosis in children. Methods:A retrospective analysis of clinical data from patients who underwent endoscopic balloon dilation for secondary subglottic stenosis between January 2017 and January 2024 at Department of Otorhinolaryngology Head and Neck Surgery, Children's Hospital of Fudan University, Shanghai. The study included 10 children （6 males, 4 females） aged between 13 days and 3 years at the time of their first procedure, with an average age of 7 months. Subglottic stenosis was graded according to the Myer-Cotton classification, with two cases classified as grade Ⅱ and eight cases as grade Ⅲ. All patients had a history of tracheal intubation, including seven for rescue purposes and three for operations. Eight cases were complicated by other conditions: two with atrial septal defect, patent ductus arteriosus, and patent foramen ovale; two with patent foramen ovale only; one with atrial septal defect and extreme deafness in the left ear; one with a brain tumor and hydrocephalus; one with a traumatic diaphragmatic hernia and hepatic rupture; and one case complicated by type Ⅰ laryngeal cleft. Prior to surgery, all children required respiratory support-seven needed high-flow oxygen while three required CPAP. Results:All ten cases underwent endoscopic balloon dilation under spontaneous respiration and general anesthesia, totaling fourteen dilations （an average of 1.4 dilations per person） without any complications. Post-surgery air permeability tests showed that eight cases had grade Ⅰ stenosis while two had grade Ⅱ stenosis. The follow-up period ranged from six months to six years （average duration: 46 months）. Following treatment, all patients no longer required respiratory support or experienced significant mobility limitations. Conclusion:Endoscopic balloon dilation under general anesthesia is deemed safe and effective in treating secondary subglottic stenosis. Early diagnosis coupled with prompt intervention can help avoid tracheotomy procedures altogether. Standard tracheoscopy combined with breathability testing represents a crucial approach to assess normal airway diameter and effectively reduce or prevent secondary subglottic stenosis following re-intubation.
Humans ; Laryngostenosis/surgery* ; Male ; Female ; Retrospective Studies ; Laryngoplasty/methods* ; Child, Preschool ; Infant ; Dilatation/methods* ; Laryngoscopy/methods* ; Treatment Outcome ; Endoscopy

One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from Glycyrrhiza uralensis Fisch, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.

Objective: To develop the matrix-matched calibration curve correction-inductively coupled plasma mass spectrometry (ICP-MS) for the determination of lead in blood. Methods: Whole blood samples and blank whole blood were pretreated by direct dilution with a solution of 0.5% nitric acid and 0.01% TritonX-100 to obtain whole blood sample solutions and matrix-matched solvents at a 10-fold dilution. The mass concentration of lead was determined by using an ICP-MS instrument in He mode. 175Lu was added online as an internal standard. The standard working curve was calibrated with the matrix-matched solvent, and the mass concentration of lead in the whole blood samples was calculated based on the standard working curve. Recovery tests were performed on whole blood blind samples by spiking, and the relative standard deviation and average recovery rate were calculated. The accuracy and precision of this method were assessed by comparing it with the method recommended in the national standard in detection of lead in three types of bovine blood lead standard materials. Results: Good linearity was shown for lead at 0.5 to 100.0 μg/L, with a correlation coefficient of 1.000. The detection limit of lead was 0.4 μg/L, and the quantitation limit was 1.3 μg/L. The relative standard deviations were 0.65% and 1.10%. The average recovery ranged from 96.89% to 99.73%. The lead determination results were all within the normal reference ranges specified by the three certified reference materials for bovine blood samples. Conclusion The matrix-matched calibration curve correction-ICP-MS is suitable for high-throughput determination of blood lead.

Objective: To examine the causal relationship between body mass index (BMI) and 25 types of autoimmune diseases (ADs) using Mendelian randomization (MR) study method. Methods: The genome-wide association study (GWAS) data for BMI and 25 types of ADs were obtained from IEU OPEN GWAS database. Single nucleotide polymorphisms (SNPs) related to BMI were used as instrumental variables, 25 types of ADs were used as study outcomes, and MR analysis was performed using inverse variance weighted (IVW) method. Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy was tested using MR-Egger regression and MR-PRESSO, and results robustness was verified with leave-one-out method. Results: Cochran's Q test showed heterogeneity of MR analysis results (P<0.05), and a random effect model was employed. The results of MR analysis showed that elevated BMI increased the incidence risks of type 1 diabetes mellitus (OR=1.519, 95%CI: 1.281-1.801), IgA nephropathy (OR=1.227, 95%CI: 1.134-1.327), adult Still disease (OR=1.002, 95%CI: 1.001-1.003), multiple sclerosis (OR=1.303, 95%CI: 1.115-1.523), narcolepsy (OR=1.029, 95%CI: 1.017-1.040), Hashimoto thyroiditis (OR=1.561, 95%CI: 1.391-1.751), autoimmune hepatitis (OR=1.481, 95%CI: 1.076-2.038), rheumatoid arthritis (OR=1.209, 95%CI: 1.054-1.386), psoriasis vulgaris (OR=1.719, 95%CI: 1.427-2.070) and pernicious anemia (OR=1.001, 95%CI: 1.000-1.002). No causal relationship was found with other ADs (all P>0.05). MR-Egger regression identified no horizontal pleiotropy of instrumental variables (all P>0.05), while MR-PRESSO test identified partial horizontal pleiotropy (all P<0.05), which remained consistent with the original results after adjustment (P>0.05). Leave-one-out analysis showed results robustness. Conclusion There are causal relationship among BMI and type 1 diabetes mellitus, IgA nephropathy, adult Still disease, multiple sclerosis, narcolepsy, Hashimoto thyroiditis, autoimmune hepatitis, rheumatoid arthritis, psoriasis vulgaris and pernicious anemia.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

BACKGROUND:With the increase of patients with cubital tunnel syndrome,ulnar groove plasty does not affect the normal anatomical structure and distribution of the ulnar nerve,which is one of the main surgical procedures for the treatment of cubital tunnel syndrome.3D printing combined with ulnar groove plasty can more accurately position the expansion depth and width of the ulnar groove to avoid some surgical complications. OBJECTIVE:To investigate the effect of 3D printing technology combined with ulnar groove plasty on nerve electrophysiology and prognosis in patients with cubital tunnel syndrome. METHODS:A total of 70 patients with moderate and severe cubital tunnel syndrome who were treated in Cangzhou Integrated Traditional Chinese and Western Medicine Hospital from March 2020 to March 2022 were selected as the study subjects.They were divided into two groups,with 35 cases in each group.The control group underwent traditional ulnar groove plasty.The observation group underwent 3D printing technology combined with ulnar groove plasty.The patients were followed up for 3 months.The clinical efficacy,latency,amplitude of compound muscle action potential of abductor pollicis brevis of the affected limb and ulnar nerve motor conduction velocity,grip strength on the affected side,pinch strength of the middle and thumb fingers,S-W monofilament of the little finger,two-point discrimination of the little finger,and Disabilities of the Arm,Shoulder and Hand Questionnaire score were compared between the two groups. RESULTS AND CONCLUSION:(1)Compared with the control group(74%),the excellent and good rate was significantly higher in the observation group(91%)(P<0.05).(2)Compared with pre-treatment,the latency of compound muscle action potential of abductor pollicis brevis of affected limb was significantly shorter and the wave amplitude and ulnar nerve motor conduction velocity were significantly higher in the two groups after treatment.The latency was significantly shorter and the wave amplitude and ulnar nerve motor conduction velocity were significantly higher in the observation group than those in the control group(P<0.05).(3)Compared with pre-treatment,the grip strength,middle finger and thumb pinch strength of the affected side,S-W monofilament of the little finger and two-point discrimination of the little finger were significantly decreased in the two groups after treatment.The grip strength,middle finger and thumb pinch strength on the affected side were greater,S-W monofilament of the little finger and two-point discrimination of the little finger were significantly smaller in the observation group than those in the control group(P<0.05).(4)Compared with pre-treatment,the Disabilities of the Arm,Shoulder and Hand Questionnaire scores of the two groups were significantly reduced after treatment,and the Disabilities of the Arm,Shoulder and Hand Questionnaire scores of the observation group were significantly lower than those of the control group(P<0.05).(5)It is concluded that 3D printing technology combined with ulnar groove plasty in the treatment of cubital tunnel syndrome can effectively improve its clinical efficacy,promote the neurophysiological recovery of patients,and enhance the function of fingers and upper limbs,which has high clinical application value.