Yan Wang’s research while affiliated with Hefei University of Technology and other places

Background Diffuse large B‐cell lymphoma (DLBCL) is predominant subtype of non‐Hodgkin lymphoma and can be effectively treated. Nevertheless, a subset of patients experiences refractory or relapsed disease, highlighting the need for new therapeutic strategies. Methods Depmap database based on CRISPR/Cas9 knock out analysis was employed to identify the essential gene SH3GL1, which encodes endophilin A2, as crucial for the proliferation and survival of DLBCL cells. Immunohistochemistry (IHC) staining was performed on the 126 paraffin‐embedded clinical DLBCL samples to investigate the association between SH3GL1 expression levels and the prognosis. To investigate the specific mechanism modulated by SH3GL1 in the progression of DLBCL, an integrative approach was employed. This approach combined high‐throughput sequencing technologies, such as Deep‐DIA and LC‐MS, with functional validation techniques, including CRISPR/Cas9 gene editing, xenograft models, and molecular pathway analyses. Results Our study found that high expression levels of SH3GL1 correlate with poor prognosis in a cohort of 126 newly diagnosed DLBCL patients, underscoring its significance in disease progression. Mechanistically, we found that SH3GL1 deficiency triggers ferritin heavy chain 1 (FTH1)‐mediated ferroptosis, specifically ferritinophagy‐induced ferroptosis, in DLBCL cells. Additionally, high expression of SH3GL1 suppresses doxorubicin‐induced ferroptosis. Cancer cells' resistance to conventional therapies is associated with increased sensitivity to ferroptosis. Conclusions These findings emphasise SH3GL1 as a promising prognostic biomarker and a potential therapeutic target in DLBCL, offering new avenues for treatment strategies aimed at overcoming drug resistance and improving patients' outcomes. Key points Elevated SH3GL1 expression in DLBCL patients was associated with a negative prognosis. SH3GL1 plays a crucial role in promoting DLBCL cell survival through the regulation of FTH1‐mediated ferroptosis and doxorubicin resistance.

Objective Xiao‐Chai‐Hu‐Tang (XCHT) has been demonstrated to exert an antidepressant effect during long‐term clinical practices. However, the potential mechanisms of XCHT remain unknown. This study aims to investigate the effect of XCHT on chronic unpredictable mild stress‐induced mice with depressive‐like behaviors and to explore the underlying mechanisms. Methods The active compositions and potential related targets of XCHT in the brain were obtained through UPLC‐Q‐TOF‐MS, network pharmacology, and bioinformatics analyses, verified by experimental validation. Then, the protein–protein interaction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and molecular docking were used to predict the core targets and mechanisms of XCHT on depression. After being treated with XCHT standard decoction, based on enzyme‐linked immunosorbent assay (ELISA), non‐targeted metabolism, targeted LC–MS analyses, RNA‐seq, quantitative RT‐PCR, immunofluorescence, and western blotting were determined to clarify the mechanism of XCHT in the treatment of anxiety and depression disorder. Results In total, 166 active ingredients and 525 related targets of XCHT were detected and selected from the network databases. The inflammatory response and metabolism of neurotransmitters were the main related signaling pathways predicted by KEGG enrichment analyses. Behavioral testing shows that XCHT has antidepressant effects, and untargeted metabolomic studies showed it significantly reduced levels of the neurotoxic substance quinoline acid. Combining the results of molecular docking, RNA‐seq, and western blot revealed that XCHT regulated nerve regeneration via BDNF/TrkB/CREB and PI3K/AKT signaling pathways. Immunofluorescence analysis revealed that XCHT downregulated the chronic stress‐induced activation of microglia and astrocytes in the hippocampus. Conclusion XCHT exerts antidepressant functions by modulating neuroinflammation and neuroregeneration.

AIM: To describe the anatomic characteristics of the lacrimal sac and its adjacent bone structures and to provide surgical recommendations for endoscopic dacryocystorhinostomy (EN-DCR). METHODS: This retrospective comparative study involved 118 sides with complete nasolacrimal duct obstruction and 83 unaffected sides from 126 patients. Computed tomographic-dacryocystography (CT-DCG) scans were performed before lacrimal surgery, and image reconstruction was used to obtain continuous 0.75-mm axial, coronal, and segmental sections for review. The morphology of the lacrimal sac and its relationship with adjacent bony structures were determined for measurement, as well as the obstructed location. RESULTS: The height of the lacrimal sac was 12.99±2.10 mm in this study. The operculum of the middle turbinate (OMT) was located vertically in the lower third of the lacrimal sac. Horizontally, the junction between the maxillary bone and the lacrimal bone (MB-LB) was close to, mostly (60.2%) posterior to, the lacrimal sac. The uncinate process was more frequently attached to the lacrimal bones (75.1%). The obstructions were generally located around the entrance of the nasolacrimal duct (NLD). However, some were placed higher, with 7.63% blocked not lower than the OMT. There was a negative correlation between the diameter of the lacrimal sac and the level of obstruction (r= -0.35, P<0.01). CONCLUSION: In this study, the OMT and MB-LB can be served as the landmarks in EN-DCR. Partial uncinectomy should be performed in most cases. The obstructions were generally located around the entrance of the NLD, but some extreme individual variations strongly implies the importance of CT-DCG scanning before surgery.

The Cri du Chat Syndrome (CdCS), a devastating genetic disorder caused by a deletion on chromosome 5p, faces challenges in finding effective treatments and accurate animal models. Using CRISPR‐Cas9, a novel CdCS rat model with a 2q22 deletion is developed, mirroring a common genetic alteration in CdCS patients. This model exhibits pronounced deficits in social behavior, cognition, and anxiety, accompanied by neuronal abnormalities and immune dysregulation in key brain regions such as the hippocampus and medial prefrontal cortex (mPFC). The immunostaining and RNA‐seq analyses provide new insights into CdCS pathogenesis, revealing inflammatory and immune processes. Importantly, it is demonstrated that early gene replacement therapy with AAV‐Ctnnd2 alleviates cognitive impairments in CdCS rats, highlighting the potential for early intervention. However, the effectiveness of this therapy is confined to the early developmental stages and does not fully restore all CdCS symptoms. The findings deepen the understanding of CdCS pathogenesis and suggest promising therapeutic directions.