Yue Zhang

Carbapenem-resistant Acinetobacter baumannii (CRAB) represents a formidable nosocomial pathogen, with healthcare environments acting as critical reservoirs for its dissemination. In this study, we investigated the prevalence, antimicrobial resistance profiles and genomic characteristics of CRAB isolates collected from hospitals in Shanghai, China, between June and December 2024, identifying ST2 ^Pas (84.13%) and ST164 ^Pas (15.08%) as the predominant lineages among the 126 CRAB isolates recovered from clinical ( n =94), environmental ( n =29) and healthcare worker ( n =3) sources. Environmental CRAB accounted for the highest proportions on patient-contact surfaces (34.48%), medical devices (31.03%) and shared items (24.14%). Within the dominant ST2 ^Pas lineage, clinical isolates exhibited higher resistance rates to ampicillin/sulbactam, cefoperazone/sulbactam and levofloxacin, with significantly higher carriage rates of bla _TEM-1D compared to environmental isolates. Compared to ST164 ^Pas , ST2 ^Pas CRAB isolates exhibited greater resistance to amikacin, gentamicin, trimethoprim/sulfamethoxazole and minocycline and a higher prevalence of aph (3′)-Ia, aph (3″)-Ib, aph(3′ )-VI, aph (6)-Id, arm A, bla _OXA-66 , bla _TEM-1D , mph (E) and tet (B), but lower rates of bla _CARB-16 , bla _NDM-1 and bla _OXA-91 ( P< 0.05). Notably, comparative genomic analysis suggested putative adaptive differences between the two lineages. ST2 ^Pas retained the T6SS and biofilm-associated genes ( bap ), descriptive genomic features that suggest a potential capacity for active colonization. Conversely, the ST164 ^Pas clone lacked the T6SS gene cluster but was enriched with the surface adhesin ata and immune evasion-related genes. Concordantly, ST164 ^Pas CRAB isolates exhibited significantly stronger biofilm-forming capacities than ST2 ^Pas in vitro . We hypothesize that these genomic alterations and phenotypic traits may represent a fitness trade-off, potentially conferring a survival advantage under antibiotic pressure. Furthermore, bla _OXA-23 in ST2 ^Pas was predominantly carried on conjugative plasmids restricted to Acinetobacter species, whereas bla _NDM-1 in ST164 ^Pas was localized on a broad-host-range non-mobile plasmid, potentially facilitating cross-genus transmission. Although our ST164 ^Pas isolates shared high homology with clinical strains from Zhejiang, China, the genomic localization of bla _NDM-1 differed between the plasmid and chromosome, respectively. These descriptive genomic findings highlight the putative adaptive trajectories of the predominant ST2 ^Pas and emerging ST164 ^Pas clones, underscoring the critical need for comprehensive genomic surveillance, complemented by future phenotypic validation, to monitor their rapid evolution and dissemination.

Purpose: A nomogram to predict shrinkage modes after neoadjuvant therapy (NAT) was constructed in HER-2 positive (HER2+) breast cancer. The value and mechanism of targeting long noncoding RNA (lncRNA) as efficacy prediction biomarker was also evaluated. Methods: All enrolled patients received six cycles of chemotherapy (Docetaxel + Carboplatin) and anti-HER-2 dual-targeted therapy (Trastuzumab + Pertuzumab) before surgery. According to pathological three-dimensional (3D) models of residual tumor from 71 HER2+ patients, shrinkage modes were divided into concentric shrinkage mode (CSM) and non-CSM (NCSM). LncRNAs in core biopsy tissues in the CSM and NCSM groups were selected by microarray and validated by RT-PCR. A nomogram was constructed to predict shrinkage modes after NAT in combination with clinical-pathological and transcriptome signatures. Cell proliferation was used CCK-8 and colony formation assay. PAPIS Kit was used to perform nuclear and cytoplasmic separation. The cell drug resistance assays were to explore the value of paclitaxel. The ChIRP-MS assay was to search RNA-binding proteins and verified by WB. Cell cycle analysis was carried out by flow cytometry. Results: Independent predictors of NCSM were lymph nodes downstaging after NAT, mammographic malignant calcification, hormone receptor expression, and RUVBL1-AS1 expression. A nomogram was constructed in combination with these predictors, which showed an area under the curve of 0.883, supporting the predictive power of the method. Overexpression of RUVBL1-AS1 inhibited HER2+ cells proliferation. Overexpression of RUVBL1-AS1 increased the number of cells in G1/S phase and decreased that of cells in G2 phase. RUVBL1-AS1 increased paclitaxel resistance and downregulated VCP expression. RUVBL1-AS1 affects cell cycle progression by downregulating VCP, resulting in the reduction of cells in G2/M phase, thereby weakening the sensitivity to paclitaxel. Conclusion: The nomogram could accurately predict shrinkage modes after NAT, and may help guide the individualized selection of breast conserving surgery candidates after NAT. RUVBL1-AS1 might be a promising therapeutic target of paclitaxel-based chemotherapy inHER2+ breast cancer.