Clinical best practices in interdisciplinary management of human epidermal growth factor receptor 2 antibody-drug conjugates-induced interstitial lung disease/pneumonitis: An expert consensus in China.

Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.

Erratum: Author correction to 'Ruscogenin alleviates LPS-triggered pulmonary endothelial barrier dysfunction through targeting NMMHC IIA to modulate TLR4 signaling' [Acta Pharmaceutica Sinica B 12 (2022) 1198-1212].

[This corrects the article DOI: 10.1016/j.apsb.2021.09.017.].

Ruscogenin alleviates LPS-triggered pulmonary endothelial barrier dysfunction through targeting NMMHC IIA to modulate TLR4 signaling.

Pulmonary endothelial barrier dysfunction is a hallmark of clinical pulmonary edema and contributes to the development of acute lung injury (ALI). Here we reported that ruscogenin (RUS), an effective steroidal sapogenin of Radix Ophiopogon japonicus, attenuated lipopolysaccharides (LPS)-induced pulmonary endothelial barrier disruption through mediating non-muscle myosin heavy chain IIA (NMMHC IIA)‒Toll-like receptor 4 (TLR4) interactions. By in vivo and in vitro experiments, we observed that RUS administration significantly ameliorated LPS-triggered pulmonary endothelial barrier dysfunction and ALI. Moreover, we identified that RUS directly targeted NMMHC IIA on its N-terminal and head domain by serial affinity chromatography, molecular docking, biolayer interferometry, and microscale thermophoresis analyses. Downregulation of endothelial NMMHC IIA expression in vivo and in vitro abolished the protective effect of RUS. It was also observed that NMMHC IIA was dissociated from TLR4 and then activating TLR4 downstream Src/vascular endothelial cadherin (VE-cadherin) signaling in pulmonary vascular endothelial cells after LPS treatment, which could be restored by RUS. Collectively, these findings provide pharmacological evidence showing that RUS attenuates LPS-induced pulmonary endothelial barrier dysfunction by inhibiting TLR4/Src/VE-cadherin pathway through targeting NMMHC IIA and mediating NMMHC IIA‒TLR4 interactions.

YiQiFuMai lyophilized injection attenuates particulate matter-induced acute lung injury in mice via TLR4-mTOR-autophagy pathway.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the serious diseases that are characterized by a severe inflammatory response of lung injuries and damage to the microvascular permeability, frequently resulting in death. YiQiFuMai (YQFM) lyophilized injection powder is a redeveloped preparation based on the well-known traditional Chinese medicine formula Sheng-Mai-San which is widely used in clinical practice in China, mainly for the treatment of microcirculatory disturbance-related diseases. However, there is little information about its role in ALI/ARDS. The aim of this study was to determine the protective effect of YQFM on particulate matter (PM)-induced ALI. The mice were intratracheally instilled with 50 mg/kg body weight of Standard Reference Material1648a (SRM1648a) in the PM-induced group. The mice in the YQFM group were given YQFM (three doses: 0.33, 0.67, and 1.34 g/kg) by tail vein injection 30 min after the intratracheal instillation of PM. The results showed that YQFM markedly reduced lung pathological injury and the lung wet/dry weight ratios induced by PM. Furthermore, we also found that YQFM significantly inhibited the PM-induced myeloperoxidase (MPO) activity in lung tissues, decreased the PM-induced inflammatory cytokines including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), reduced nitric oxide (NO) and total protein in bronchoalveolar lavage fluids (BALF), and effectively attenuated PM-induced increases lymphocytes in BALF. In addition, YQFM increased mammalian target of rapamycin (mTOR) phosphorylation and dramatically suppressed the PM-stimulated expression of toll-like receptor 4 (TLR4), MyD88, autophagy-related protein LC3Ⅱand Beclin 1 as well as autophagy. In conclusion, these findings indicate that YQFM had a critical anti-inflammatory effect due to its ability to regulate both TLR4-MyD88 and mTOR-autophagy pathways, and might be a possible therapeutic agent for PM-induced ALI.