The incidence of lung cancer (LC) in chronic obstructive pulmonary disease (COPD) patients is dozens of times higher than that in patients without COPD. Elevated activity of nuclear factor-k-gene binding (NF-κB) was found in lung tissue of patients with COPD, and the continuous activation of NF-κB is observed in both malignant transformation and tumor progression of LC, suggesting that NF-κB and its regulators may play a key role in the progression of LC in COPD patients. Here, we report for the first time that a key long non-coding RNA (lncRNA)-ICL involved in the regulation of NF-κB activity in LC tissues of COPD patients. The analyses showed that the expression of ICL significantly decreased in LC tissues of LC patients with COPD than that in LC tissues of LC patients without COPD. Functional experiments in vitro showed that exogenous ICL only significantly inhibited the proliferation, invasion and migration in primary tumor cells of LC patients with COPD compared to LC patients without COPD. Mechanism studies have shown that ICL could suppress the activation of NF-κB by blocking the hsa-miR19-3p/NKRF/NF-κB pathway as a microRNA sponge. Furthermore, In vivo experiments showed that exogenous ICL effectively inhibited the growth of patient-derived subcutaneous tumor xenografts (PDX) of LC patients with COPD and significantly prolonged the survival time of tumor-bearing mice. In a word, our study shows that the decrease of ICL is associated with an increased risk of LC in patients with COPD, ICL is not only expected to be a new therapeutic target for LC in COPD patients, but also has great potential to be used as a new marker for evaluating the occurrence, severity stratification and prognosis of LC in patients with COPD.

BackgroundMany COVID-19 patients have been discharged, but lung injury, including pulmonary fibrosis, might lead to long-term impairment. This study aimed to evaluate predictors and monitors of pulmonary fibrosis in patients with COVID-19.MethodsThirty-five convalescent patients with severe COVID-19, after appropriate medical treatments, were recruited. According to evidence of fibrosis on initial computed tomography (CT), the patients were divided into mild-to-moderate and severe groups. Levels of transforming growth factor beta (TGF-β), chemokine ligand 18 (CCL18), type III procollagen peptide (PⅢP), hyaluronic acid (HA), laminin (LN), and type IV collagen (CⅣ) were determined. Laboratory tests, clinical data, and CT features at different stages were collected and analyzed, and the prognostic performance of these parameters was evaluated.ResultsSevere fibrosis was found in 76.29% (26/35) of patients. However, most baseline laboratory characteristics were normal. Fibrosis indicators (TGF-β: 66.67±158.57 vs 55.84±126.43 pg/mL, P=0.006; CCL18: 364.27±167.70 vs 84.47±60.67 ng/mL, P=0.000; PⅢP: 54.12±55.34 vs 17.15±2.48 ng/mL, P=0.000; HA: 122.47±78.84 vs 59.74±18.01 ng/mL, p=0.000; LN: 55.43±46.44 vs 24.25±7.79 ng/mL, P=0.000; CⅣ: 24.77±14.97 vs 15.32±1.15 ng/mL, P=0.001) were elevated in patients compared with controls. Over 90 days’ follow-up, HRCT scores gradually decreased from 22.48±16.13 to 10.33±11.11 (P<0.001), and mMRC scores decreased from 3.27±0.32 to 1.48±0.33, and all fibrosis indicators, except for PⅢP, gradually declined with the improvement of pulmonary fibrosis. Moreover, TGF-β and CCL18 levels were lower in the mild-to-moderate than severe fibrosis group (88.16±97.45 vs 205.93±170.57 pg/mL, P=0.024; 241.84±125.37 vs 366.64±161.06 ng/mL, P=0.038), and patients with elevated baseline levels of serum TGF-β and CCL18 had longer rehabilitation times.ConclusionsTGF-β and CCL18 may be promising biomarkers for predicting and monitoring the development of pulmonary fibrosis in patients with COVID-19.

Aims: To improve the countermeasures of clinical trial institutions against major public health events such as COVID-19. Methods: A questionnaire was created to investigate the effects of the global static management policy against COVID-19 on clinical trials in Shanghai in 2022. And the convenience sampling combined with snowball sampling were adopted to interview clinical research coordinators (CRC) and clinical research associates(CRA) on the platform of SOJUMP as well as WeChat. Results: 156 valid questionnaires were collected, with an effective recovery rate of 93.98%. 98.07% of the respondents believed that the effects was severe. The extent of effects on different links of clinical trials was different (rank sum test P<0.01), being great on medication/follow-up (76.28% of significant effects), monitoring/audit (74.36%) and screening/admission (71.79%).The protocol deviations associated with out of visit window (experienced by 94.23% of respondents, during the static management policy), inspection (78.85%), medication (67.95%) and withdrawal (62.82%). And the interviewees reported 49.66% of the exclusion should blame the epidemic situation. The development of online-office or remote-ethics meetings alleviated the impact of lockdown policy on approval/ethics/contract and data cleaning/site closing. 90.98% of oral drugs could be sent by express delivery, but only 1.28% had the experience of online informed consent and remote inspection. Conclusions: We shall speed up the application of the intelligent clinical trial system and remote monitoring system, realize the transformation to a new model of patient-centered clinical trial, and improve the ability to cope with major public health events such as COVID-19.