Leritrelvir for the treatment of mild or moderate COVID-19 without co-administered ritonavir: a multicentre randomised, double-blind, placebo-controlled phase 3 trial.

Background: Leritrelvir is a novel α-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease. A preclinical study has demonstrated leritrelvir poses similar antiviral activities towards different SARS-CoV-2 variants compared with nirmatrelvir. A phase 2 clinical trial has shown a comparable antiviral efficacy and safety between leritrelvir with and without ritonavir co-administration. This trial aims to test efficacy and safety of leritrelvir monotherapy in adults with mild-to-moderate COVID-19. Methods: This was a randomised, double-blind, placebo-controlled, multicentre phase 3 trial at 29 clinical sites in China. Enrolled patients were from 18 to 75 years old, diagnosed with mild or moderate COVID-19 and not requiring hospitalization. Patients had a positive SARS-CoV-2 nucleic acid test (NAT) and at least one of the COVID-19 symptoms within 48 h before randomization, and the interval between the first positive SARS-CoV-2 NAT and randomization was ≤120 h (5 days). Patients were randomly assigned in a 1:1 ratio to receive a 5-day course of either oral leritrelvir 400 mg TID or placebo. The primary efficacy endpoint was the time from the first dose to sustained clinical recovery of all 11 symptoms (stuffy or runny nose, sore throat, shortness of breath or dyspnea, cough, muscle or body aches, headache, chills, fever ≥37 °C, nausea, vomiting, and diarrhea). The safety endpoint was the incidence of adverse events (AE). Primary and safety analyses were performed in the intention-to-treat (ITT) population. This study is registered with ClinicalTrials.gov, NCT05620160. Findings: Between Nov 12 and Dec 30, 2022 when the zero COVID policy was abolished nationwide, a total of 1359 patients underwent randomization, 680 were assigned to leritrelvir group and 679 to placebo group. The median time to sustained clinical recovery in leritrelvir group was significantly shorter (251.02 h [IQR 188.95-428.68 h]) than that of Placebo (271.33 h [IQR 219.00-529.63 h], P = 0.0022, hazard ratio [HR] 1.20, 95% confidence interval [CI], 1.07-1.35). Further analysis of subgroups for the median time to sustained clinical recovery revealed that (1) subgroup with positive viral nucleic acid tested ≤72 h had a 33.9 h difference in leritrelvir group than that of placebo; (2) the subgroup with baseline viral load >8 log 10 Copies/mL in leritrelvir group had 51.3 h difference than that of placebo. Leritrelvir reduced viral load by 0.82 log10 on day 4 compared to placebo. No participants in either group progressed to severe COVID-19 by day 29. Adverse events were reported in two groups: leritrelvir 315 (46.46%) compared with placebo 292 (43.52%). Treatment-relevant AEs were similar 218 (32.15%) in the leritrelvir group and 186 (27.72%) in placebo. Two cases of COVID-19 pneumonia were reported in placebo group, and one case in leritrelvir group, none of them were considered by the investigators to be leritrelvir related. The most frequently reported AEs (occurring in ≥5% of participants in at least one group) were laboratory finding: hypertriglyceridemia (leritrelvir 79 [11.7%] vs. placebo 70 [10.4%]) and hyperlipidemia (60 [8.8%] vs. 52 [7.7%]); all of them were nonserious. Interpretation: Leritrelvir monotherapy has good efficacy for mild-to-moderate COVID-19 and without serious safety concerns. Funding: This study was funded by the National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project and R&D Program of Guangzhou Laboratory.

Construction and evaluation of a nomogram for predicting survival in patients with lung cancer.

BACKGROUND: Lung cancer is a heterogeneous disease with a severe disease burden. Because the prognosis of patients with lung cancer varies, it is critical to identify effective biomarkers for prognosis prediction. METHODS: A total of 2325 lung cancer patients were integrated into four independent sets (training set, validation set I, II and III) after removing batch effects in our study. We applied the microarray data algorithm to screen the differentially expressed genes in the training set. The most robust markers for prognosis were identified using the LASSO-Cox regression model, which was then used to create a Cox model and nomogram. RESULTS: Through LASSO and multivariate Cox regression analysis, eight genes were identified as prognosis-associated hub genes, followed by the creation of prognosis-associated risk scores (PRS). The results of the Kaplan-Meier analysis in the three validation sets demonstrate the good predictive performance of PRS, with hazard ratios of 2.38 (95% confidence interval (CI), 1.61-3.53) in the validation set I, 1.35 (95% CI, 1.06-1.71) in the validation set II, and 2.71 (95% CI, 1.77-4.18) in the validation set III. Additionally, the PRS demonstrated superior survival prediction in subgroups by age, gender, p-stage, and histologic type (p < 0.0001). The complex model integrating PRS and clinical risk factors also have a good predictive performance for 3-year overall survival. CONCLUSIONS: In this study, we developed a PRS signature to help predict the survival of lung cancer. By combining it with clinical risk factors, a nomogram was established to quantify the individual risk assessments.

Primary pulmonary Ewing's sarcoma: rare cause of massive hemothorax in a young girl-case report.

BACKGROUND: Ewing's sarcoma is a common malignant bone tumor in children and young adults. Rarely, extra-skeletal soft tissues and visceral organs can also be the site of origin of Ewing's sarcoma. Primary pulmonary Ewing's sarcoma is an extremely rare malignancy. CASE PRESENTATION: We report an unusual case of primary pulmonary Ewing's sarcoma in a 15-year-old girl who initially presented with massive hemothorax. By histopathology evaluation of surgical biopsy specimens, the diagnosis of extraosseous Ewing's sarcoma was confirmed by both light microscopy and immunohistochemistry. Emergency, open surgery was performed by thoracic surgery at an early stage. After 3 cycles of chemotherapy, the patient was found to be stable at follow-up examination. No more hydrothorax or other symptoms. CONCLUSIONS: We have described an extremely rare case of primary pulmonary Ewing's sarcoma with massive hemothorax. The patient underwent surgical resection and postoperative chemotherapy, no sign of recurrence to date as an outcome.

A Case of Systemic Lupus Erythematosus with Malignant Pleural Mesothelioma in a 42-year Woman.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease characterised by inflammation. Malignant pleural mesothelioma (MPM) is a highly invasive malignant tumor derived from pleural mesothelial cells. Here, we report a case of SLE with MPM. A 42-year woman with no exposure to asbestos presented with severe left chest pain. Initially, we diagnosed her with SLE because of the clinical manifestations and high antinuclear antibody titer. Finally, a diagnosis of MPM was made, based on pleural biopsy. Her condition was under control after one cycle of chemotherapy and oral methotrexate. However, three years later, she was admitted with dyspnea, mild orthopnea, and tachycardia, and died one month later after discontinuing treatment. MPM is rare, and MPM with SLE is even rarer. We should pay attention to pleural effusion when diagnosing SLE. If possible, a pleural biopsy should be performed to reduce misdiagnosis and missed diagnosis. Key Words: Pleural effusion, Systemic lupus erythematosus (SLE), Mesothelioma.

COPB2 promotes metastasis and inhibits apoptosis of lung adenocarcinoma cells through functioning as a target of miR-216a-3p.

BACKGROUND: Lung adenocarcinoma is a non-small cell lung cancer with a high mortality. There is little published data on the role of coatomer protein complex subunit ß (COPB2) in lung adenocarcinoma. The current study aimed to explore the effects of COPB2 on lung adenocarcinoma cells. METHODS: The differential expression of COPB2 in normal cells and lung adenocarcinoma cells was detected by quantitative real time-polymerase chain reaction (qRT-PCR) and Western blotting. Then, cell viability assay, flow cytometry and Transwell experiments were performed to study the effects of COPB2 on cell growth, apoptosis, migration and invasion. MiRNA targeting COPB2 was predicted by TargetScan and validated by luciferase assay, qRT-PCR and Western blotting. The effects of miRNA inhibitor on siCOPB2 were analyzed by rescue experiments. Finally, apoptosis and metastatic marker proteins were detected by Western blotting. RESULTS: COPB2 was high-expressed in lung adenocarcinoma cells. Silencing COPB2 inhibited cell viability and cell metastasis, and significantly increased apoptosis. MiR-216a-3p was predicted to be able to target COBP2. Rescue experiment showed that miR-216a-3p inhibitor promoted cell viability, migration and invasion, and inhibited apoptosis of lung adenocarcinoma cells, partly reversed the effects of siCOPB2. Moreover, Western blotting showed that siCOPB2 up-regulated expressions of cleaved Caspase-3, Caspase-3, BCL2 associated X (Bax), and E-Cadherin, and down-regulated expressions of BCL2 apoptosis regulator (Bcl-2), N-Cadherin, and Vimentin, and the above effects were also partly reversed by miR-216a-3p inhibitor. CONCLUSIONS: High-expressed COPB2 promotes metastasis and inhibits apoptosis of lung adenocarcinoma cells through functioning as a target of miR-216a-3p.