A B S T R A C TPurpose: To evaluate the diagnostic value of computed tomography (CT) and real-time reverse-transcriptasepolymerase chain reaction (rRT-PCR) for COVID-19 pneumonia. Methods: This retrospective study included all patients with COVID-19 pneumonia suspicion, who were examined by both CT and rRT-PCR at initial presentation. The sensitivities of both tests were then compared. For patients with a final confirmed diagnosis, clinical and laboratory data, in addition to CT imaging findings were evaluated. Results: A total of 36 patients were finally diagnosed with COVID-19 pneumonia. Thirty-five patients had abnormal CT findings at presentation, whereas one patient had a normal CT. Using rRT-PCR, 30 patients were tested positive, with 6 cases initially missed. Amongst these 6 patients, 3 became positive in the second rRT-PCR assay(after 2 days, 2 days and 3 days respectively), and the other 3 became positive only in the third round of rRT-PCR tests(after 5 days, 6 days and 8 days respectively). At presentation, CT sensitivity was therefore 97.2%, whereas the sensitivity of initial rRT-PCR was only 83.3%. Conclusion: rRT-PCR may produce initial false negative results. We suggest that patients with typical CT findings but negative rRT-PCR results should be isolated, and rRT-PCR should be repeated to avoid misdiagnosis.

Background Health care workers, especially frontline nurses, faced great challenges during the coronavirus disease 2019 (COVID-19) outbreak. Aims To assess the magnitude of the psychological status and associated risk factors among nurses in the pandemic center in Wuhan, China. Methods In this study, we enrolled nurses from Renmin Hospital of Wuhan University. The questionnaire was designed to obtain basic information of the participants, and included four psychological assessment scales. We issued the questionnaires at two different points of time. We conducted the first survey on January 29 to February 2 (outbreak period) with 709 eligible responses, and the second survey on February 26 to February 28 (stable period) with 621 eligible responses. The nurses from Wuchang Fangcang shelter hospital were also enrolled in the second survey. Results During the pandemic, over one-third of nurses suffered from depression, anxiety, and insomnia. In the outbreak period, the nurses showed significantly higher risks for depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms than those in the stable period ( P < 0.01). Notably, the nurses from the Fangcang shelter hospitals were more likely to present psychological problems than those from other frontline or non-frontline (all P < 0.001) units, especially for insomnia (38.3% with severe insomnia). The nurses from the frontline, with worse physical condition and uncertain concerns about this pandemic as compared to the others, were more likely to bear psychological problems. Thus, online psychological information and sufficient protection conditions were effective interventions to help mitigate psychological distress. The nurses from Fangcang shelter hospitals suffered a significantly higher risk of psychological problems than those from other units. Conclusion The psychological status of nurses needs more attention during the COVID-19 pandemic, especially for those who fought in the frontline during the peak of the outbreak.

Proteasomes are attractive emerging targets for anti-cancer therapies. Auranofin (Aur), a gold-containing compound clinically used to treat rheumatic arthritis, was recently approved by US Food and Drug Administration for Phase II clinical trial to treat cancer but its anti-cancer mechanism is poorly understood. Here we report that (i) Aur shows proteasome-inhibitory effect that is comparable to that of bortezomib/Velcade (Vel); (ii) different from bortezomib, Aur inhibits proteasome-associated deubiquitinases (DUBs) UCHL5 and USP14 rather than the 20S proteasome; (iii) inhibition of the proteasome-associated DUBs is required for Aur-induced cytotoxicity; and (iv) Aur selectively inhibits tumor growth in vivo and induces cytotoxicity in cancer cells from acute myeloid leukemia patients. This study provides important novel insight into understanding the proteasome-inhibiting property of metal-containing compounds. Although several DUB inhibitors were reported, this study uncovers the first drug already used in clinic that can inhibit proteasome-associated DUBs with promising anti-tumor effects.

Purpose Chronic myelogenous leukemia (CML) is characterized by the constitutive activation of Bcr-Abl tyrosine kinase. Bcr-Abl-T315I is the predominant mutation that causes resistance to imatinib, cytotoxic drugs, and the second-generation tyrosine kinase inhibitors. The emergence of imatinib resistance in patients with CML leads to searching for novel approaches to the treatment of CML. Gambogic acid, a small molecule derived from Chinese herb gamboges, has been approved for phase II clinical trial for cancer therapy by the Chinese Food and Drug Administration (FDA). In this study, we investigated the effect of gambogic acid on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or wild-type Bcr-Abl. Experimental Design CML cell lines (KBM5, KBM5-T315I, and K562), primary cells from patients with CML with clinical resistance to imatinib, and normal monocytes from healthy volunteers were treated with gambogic acid, imatinib, or their combination, followed by measuring the effects on cell growth, apoptosis, and signal pathways. The in vivo antitumor activity of gambogic acid and its combination with imatinib was also assessed with nude xenografts. Results Gambogic acid induced apoptosis and cell proliferation inhibition in CML cells and inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Our data suggest that GA-induced proteasome inhibition is required for caspase activation in both imatinib-resistant and -sensitive CML cells, and caspase activation is required for gambogic acid–induced Bcr-Abl downregulation and apoptotic cell death. Conclusions These findings suggest an alternative strategy to overcome imatinib resistance by enhancing Bcr-Abl downregulation with the medicinal compound gambogic acid, which may have great clinical significance in imatinib-resistant cancer therapy.