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The COVID-19 pandemic has caused numerous deaths around the world. A growing body of evidence points to the important role of overwhelming inflammatory responses in the pathogenesis of COVID-19 and the effectiveness of anti-inflammation therapy against COVID-19 is emerging. In addition to affecting the lungs, COVID-19 can be a severe systemic inflammatory disease that is related to endothelial dysfunction. We are calling for closer attention to endothelial dysfunction in COVID-19 not only for fully revealing the pathogenic mechanism of COVID-19 but also for properly adjusting the strategy of clinical intervention.

Weijian Hang ,   Chen Chen   et al.
Synthetic lethal screening, which exploits the combination of mutations that result in cell death, is a promising method for identifying novel drug targets. This method provides a new avenue for targeting “undruggable” proteins, such as c-Myc. Here, we revisit current methods used to target c-Myc and discuss the important functional nodes related to c-Myc in non-oncogene addicted network, whose inhibition may cause a catastrophe for tumor cell destiny but not for normal cells. We further discuss strategies to identify these functional nodes in the context of synthetic lethality. We review the progress and shortcomings of this research field and look forward to opportunities offered by synthetic lethal screening to treat tumors potently.

Chen Wang ,   Hui Fang   et al.
Tocilizumab has been reported to attenuate the “cytokine storm” in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI ?7.19%–21.23%, = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 ( = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI ?99.17% to ?17.50%, = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.

Dongsheng Wang ,   Binqing Fu   et al.
Stevens--Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe diseases. This study aimed to validate the predictive ability of risk models in patients with SJS/TEN and propose possible refinement in China. Patients in the Department of Dermatology of Huashan Hospital from January 2008 to January 2019 were included. Results showed that the severity-of-illness score for TEN (SCORTEN) had a good discrimination (area under the receiver operating characteristic curve (AUC), 0.78), and it was superior to auxiliary score (AS) and ABCD-10, which indicates age, bicarbonate level, cancer, dialysis, and 10% involved body surface area (AUC, 0.69 and 0.68, respectively). The calibration of SCORTEN (Hosmer–Lemeshow goodness-of-fit test, = 0.69) was also better than that of AS ( = 0.25) and ABCD-10 ( = 0.55). SCORTEN and ABCD-10 were similar (Brier score (BS), 0.04 and 0.04) in terms of accuracy of predictions. In addition, the imaging appearance of pulmonary consolidation on computed tomography was associated with high mortality. Refined models were formed using the variables and this imaging appearance. The refined AS and ABCD-10 models were similar in discrimination compared with the original SCORTEN (0.74 vs. 0.78, = 0.23; 0.74 vs. 0.78, = 0.30, respectively). Therefore, SCORTEN showed good discrimination performance, calibration, and accuracy, and refined AS or ABCD-10 model may be an option when SCORTEN variables are not available.

Yanhong Shou ,   Lu Yang   et al.

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