Browsing by Author "Zhang, Yuan"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    A Network Meta-analysis of Dexamethasone for Preventing Post-Extubation Upper Airway Obstruction in Children
    (American Thoracic Society Journals, 2022-08-17) Iyer, Narayan Prabhu; López-Fernández, Yolanda M.; González-Dambrauskas, Sebastián; Baranwal, Arun K.; Hotz, Justin C.; Zhu, Meng; Zhang, Yuan; Craven, Hannah J.; Whipple, Elizabeth C.; Abu-Sultaneh, Samer; Khemani, Robinder G.
    RATIONALE: Peri-extubation corticosteroids are commonly used in children to prevent upper airway obstruction (UAO). However, the best timing and dose combination of corticosteroids is unknown. OBJECTIVES: To compare effectiveness of different corticosteroid regimens in preventing UAO and reintubation. METHODS: MEDLINE, CINAHL and Embase search identified randomized trials in children using corticosteroids to prevent UAO. All studies used dexamethasone. The studies were categorized based on timing of initiation of dexamethasone (early use: >12 hours prior to extubation) and the dose (high dose: (>/= 0.5mg/kg/dose). We performed Bayesian network meta-analysis (NMA) with studies grouped into four regimens- High dose, Early use (HE); Low dose, Early use (LE); High dose, Late use (HL) and Low dose, Late use (LL). RESULTS: 8 trials (n=903) were included in the analysis. For preventing UAO, (odds ratio, 95% credible interval), HE (0.13; 0.04, 0.36), HL (0.39; 0.19, 0.74) and LE (0.15; 0.04, 0.58) regimens appear to be more effective compared to no dexamethasone (low certainty). HE and LE had the highest probability of being the top ranked regimens for preventing UAO [surface under the cumulative ranking (SUCRA) 0.901 and 0.808 respectively]. For preventing reintubation, the effect estimate was imprecise for all four dexamethasone regimens compared to no dexamethasone (very low certainty). HE and LE were the top ranked regimens (SUCRA 0.803 and 0.720 respectively) for preventing reintubation. Sensitivity analysis showed that regimens which started >12 hours prior to extubation were likely more effective than regimens started >6 hours prior to extubation. CONCLUSIONS: Peri-extubation dexamethasone can prevent post-extubation UAO in children but effectiveness is highly dependent on timing and dosing regimen. Early initiation (ideally >12 hours prior to extubation) appears to be more important than the dose of dexamethasone. Ultimately the specific steroid strategy should be personalized considering the potential for adverse events associated with dexamethasone and the individual risk of UAO and reintubation.
  • Thumbnail Image
    Item
    Systematic review and meta-analysis of outcomes in patients with suspected pulmonary embolism
    (American Society of Hematology, 2021-04-27) Patel, Parth; Patel, Payal; Bhatt, Meha; Braun, Cody; Begum, Housne; Nieuwlaat, Robby; Khatib, Rasha; Martins, Carolina C.; Zhang, Yuan; Etxeandia-Ikobaltzeta, Itziar; Varghese, Jamie; Alturkmani, Hani; Bahaj, Waled; Baig, Mariam; Kehar, Rohan; Mustafa, Ahmad; Ponnapureddy, Rakesh; Sethi, Anchal; Thomas, Merrill; Wooldridge, David; Lim, Wendy; Bates, Shannon M.; Lang, Eddy; Le Gal, Grégoire; Haramati, Linda B.; Kline, Jeffrey A.; Righini, Marc; Wiercioch, Wojtek; Schünemann, Holger; Mustafa, Reem A.; Emergency Medicine, School of Medicine
    Prompt evaluation and therapeutic intervention of suspected pulmonary embolism (PE) are of paramount importance for improvement in outcomes. We systematically reviewed outcomes in patients with suspected PE, including mortality, incidence of recurrent PE, major bleeding, intracranial hemorrhage, and postthrombotic sequelae. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. We included 22 studies with 15 865 patients. Among patients who were diagnosed with PE and discharged with anticoagulation, 3-month follow-up revealed that all-cause mortality was 5.69% (91/1599; 95% confidence interval [CI], 4.56-6.83), mortality from PE was 1.19% (19/1597; 95% CI, 0.66-1.72), recurrent venous thromboembolism (VTE) occurred in 1.38% (22/1597; 95% CI: 0.81-1.95), and major bleeding occurred in 0.90% (2/221%; 95% CI, 0-2.15). In patients with a low pretest probability (PTP) and negative D-dimer, 3-month follow-up revealed mortality from PE was 0% (0/808) and incidence of VTE was 0.37% (4/1094; 95% CI: 0.007-0.72). In patients with intermediate PTP and negative D-dimer, 3-month follow-up revealed that mortality from PE was 0% (0/2747) and incidence of VTE was 0.46% (14/3015; 95% CI: 0.22-0.71). In patients with high PTP and negative computed tomography (CT) scan, 3-month follow-up revealed mortality from PE was 0% (0/651) and incidence of VTE was 0.84% (11/1302; 95% CI: 0.35-1.34). We further summarize outcomes evaluated by various diagnostic tests and diagnostic pathways (ie, D-dimer followed by CT scan).
  • Thumbnail Image
    Item
    USP21 deubiquitylates Nanog to regulate protein stability and stem cell pluripotency
    (Nature Publishing group, 2016-11-04) Liu, Xingyu; Yao, Yuying; Ding, Huiguo; Han, Chuanchun; Chen, Yuhan; Zhang, Yuan; Wang, Chanjuan; Zhang, Xin; Zhang, Yiling; Zhai, Yun; Wang, Ping; Wei, Wenyi; Zhang, Jing; Zhang, Lingqiang; Microbiology and Immunology, School of Medicine
    The homeobox transcription factor Nanog has a vital role in maintaining pluripotency and self-renewal of embryonic stem cells (ESCs). Stabilization of Nanog proteins is essential for ESCs. The ubiquitin–proteasome pathway mediated by E3 ubiquitin ligases and deubiquitylases is one of the key ways to regulate protein levels and functions. Although ubiquitylation of Nanog catalyzed by the ligase FBXW8 has been demonstrated, the deubiquitylase that maintains the protein levels of Nanog in ESCs yet to be defined. In this study, we identify the ubiquitin-specific peptidase 21 (USP21) as a deubiquitylase for Nanog, but not for Oct4 or Sox2. USP21 interacts with Nanog protein in ESCs in vivo and in vitro. The C-terminal USP domain of USP21 and the C-domain of Nanog are responsible for this interaction. USP21 deubiquitylates the K48-type linkage of the ubiquitin chain of Nanog, stabilizing Nanog. USP21-mediated Nanog stabilization is enhanced in mouse ESCs and this stabilization is required to maintain the pluripotential state of the ESCs. Depletion of USP21 in mouse ESCs leads to Nanog degradation and ESC differentiation. Overall, our results demonstrate that USP21 maintains the stemness of mouse ESCs through deubiquitylating and stabilizing Nanog.