Browsing by Author "Zhou, Hong"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    A National Comparison of Operative Outcomes of New and Experienced Surgeons
    (Wolters Kluwer, 2021) Kelz, Rachel R.; Sellers, Morgan M.; Niknam, Bijan A.; Sharpe, James E.; Rosenbaum, Paul R.; Hill, Alexander S.; Zhou, Hong; Hochman, Lauren L.; Bilimoria, Karl Y.; Itani, Kamal; Romano, Patrick S.; Silber, Jeffrey H.; Surgery, School of Medicine
    Objective: To determine whether outcomes achieved by new surgeons are attributable to inexperience or to differences in the context in which care is delivered and patient complexity. Background: Although prior studies suggest that new surgeon outcomes are worse than those of experienced surgeons, factors that underlie these phenomena are poorly understood. Methods: A nationwide observational tapered matching study of outcomes of Medicare patients treated by new and experienced surgeons in 1221 US hospitals (2009-2013). The primary outcome studied is 30-day mortality. Secondary outcomes were examined. Results: In total, 694,165 patients treated by 8503 experienced surgeons were matched to 68,036 patients treated by 2119 new surgeons working in the same hospitals. New surgeons' patients were older (25.8% aged ≥85 vs 16.3%,P<0.0001) with more emergency admissions (53.9% vs 25.8%,P<0.0001) than experienced surgeons' patients. Patients of new surgeons had a significantly higher baseline 30-day mortality rate compared with patients of experienced surgeons (6.2% vs 4.5%,P<0.0001;OR 1.42 (1.33, 1.52)). The difference remained significant after matching the types of operations performed (6.2% vs 5.1%, P<0.0001; OR 1.24 (1.16, 1.32)) and after further matching on a combination of operation type and emergency admission status (6.2% vs 5.6%, P=0.0007; OR 1.12 (1.05, 1.19)). After matching on operation type, emergency admission status, and patient complexity, the difference between new and experienced surgeons' patients' 30-day mortality became indistinguishable (6.2% vs 5.9%,P=0.2391;OR 1.06 (0.97, 1.16)). Conclusions: Among Medicare beneficiaries, the majority of the differences in outcomes between new and experienced surgeons are related to the context in which care is delivered and patient complexity rather than new surgeon inexperience.
  • Thumbnail Image
    Item
    Hypoxic Upregulation of IER2 Increases Paracrine GMFG Signaling of Endoplasmic Reticulum Stress-CAF to Promote Chordoma Progression via Targeting ITGB1
    (Wiley, 2024) Zhang, Tao-Lan; Zheng, Bo-Wen; Xia, Chao; Wu, Peng-Fei; Zheng, Bo-Yv; Jiang, Ling-Xiang; Li, Jing; Lv, Guo-Hua; Zhou, Hong; Huang, Wei; Zou, Ming-Xiang; Radiation Oncology, School of Medicine
    Currently, the oncogenic mechanism of endoplasmic reticulum stress-CAF (ERS-CAF) subpopulation in chordoma remains unknown. Here, single-cell RNA sequencing, spatial transcriptomics, GeoMx Digital Spatial Profiler, data-independent acquisition proteomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence are used to unveil the precise molecular mechanism of how ERS-CAF affected chordoma progression. Results show that hypoxic microenvironment reprograms CAFs into ERS-CAF subtype. Mechanistically, this occurrs via hypoxia-mediated transcriptional upregulation of IER2. Overexpression of IER2 in CAFs promotes chordoma progression, which can be impeded by IER2 knockdown or use of ERS inhibitors. IER2 also induces expression of ERS-CAF marker genes and results in production of a pro-tumorigenic paracrine GMFG signaling, which exert its biological function via directly binding to ITGB1 on tumor cells. ITGB1 inhibition attenuates tumor malignant progression, which can be partially reversed by exogenous GMFG intervention. Further analyses reveal a positive correlation between ITGB1high tumor cell counts and SPP1+ macrophage density, as well as the spatial proximity of these two cell types. Clinically, a significant correlation of high IER2/ITGB1 expression with tumor aggressive phenotype and poor patient survival is observed. Collectively, the findings suggest that ERS-CAF regulates SPP1+ macrophage to aggravate chordoma progression via the IER2/GMFG/ITGB1 axis, which may be targeted therapeutically in future.
  • Thumbnail Image
    Item
    The vitamin D receptor is involved in the regulation of human breast cancer cell growth via a ligand-independent function in cytoplasm
    (Impact Journals, 2017-04-18) Trivedi, Trupti; Zheng, Yu; Fournier, Pierrick G.J.; Murthy, Sreemala; John, Sutha; Schillo, Suzanne; Dunstan, Colin R.; Mohammad, Khalid S.; Zhou, Hong; Seibel, Markus J.; Guise, Theresa A.; Medicine, School of Medicine
    Vitamin D has pleiotropic effects on multiple tissues, including malignant tumors. Vitamin D inhibits breast cancer growth through activation of the vitamin D receptor (VDR) and via classical nuclear signaling pathways. Here, we demonstrate that the VDR can also function in the absence of its ligand to control behaviour of human breast cancer cells both outside and within the bone microenvironment. Stable shRNA expression was used to knock down VDR expression in MCF-7 cells, generating two VDR knockdown clonal lines. In ligand-free culture, knockdown of VDR in MCF-7 cells significantly reduced proliferation and increased apoptosis, suggesting that the VDR plays a ligand-independent role in cancer cell growth. Implantation of these VDR knockdown cells into the mammary fat pad of nude mice resulted in reduced tumor growth in vivo compared with controls. In the intra-tibial xenograft model, VDR knockdown greatly reduced the ability of the cells to form tumors in the bone microenvironment. The in vitro growth of VDR knockdown cells was rescued by the expression of a mutant form of VDR which is unable to translocate to the nucleus and hence accumulates in the cytoplasm. Thus, our data indicate that in the absence of ligand, the VDR promotes breast cancer growth both in vitro and in vivo and that cytoplasmic accumulation of VDR is sufficient to produce this effect in vitro. This new mechanism of VDR action in breast cancer cells contrasts the known anti-proliferative nuclear actions of the VDR-vitamin D ligand complex.