Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Metastasis is crucial for the mortality of non-small cell lung carcinoma (NSCLC) patients. The epithelial-mesenchymal transition (EMT) plays a critical role in regulating tumor metastasis. Glioma-associated oncogene 1 (Gli1) is aberrantly active in a series of tumor tissues. However, the molecular regulatory relationships between Gli1 and NSCLC metastasis have not yet been identified. Herein, we reported Gli1 promoted NSCLC metastasis. High Gli1 expression was associated with poor survival of NSCLC patients. Ectopic expression of Gli1 in low metastatic A549 and NCI-H460 cells enhanced their migration, invasion abilities and facilitated EMT process, whereas knock-down of Gli1 in high metastatic NCI-H1299 and NCI-H1703 cells showed an opposite effect. Notably, Gli1 overexpression accelerated the lung and liver metastasis of NSCLC in the intravenously injected metastasis model. Further research showed that Gli1 positively regulated Snail expression by binding to its promoter and enhancing its protein stability, thereby facilitating the migration, invasion and EMT of NSCLC. In addition, administration of GANT-61, a Gli1 inhibitor, obviously suppressed the metastasis of NSCLC. Collectively, our study reveals that Gli1 is a critical regulator for NSCLC metastasis and suggests that targeting Gli1 is a prospective therapy strategy for metastatic NSCLC.

Objective:To explore risk factors of in-stent restenosis (ISR) after vertebral artery stenting (VAS) in patients with ischemic cerebrovascular disease.Methods:Case-control studies and cohort studies on risk factors for ISR after VAS in patients with ischemic cerebrovascular disease were searched from CNKI, VIP, Wanfang, Chinese Biomedical literature Database, PubMed, Embase and Cochrane Library. The retrieval time limit was the establishment of each database until May 31, 2021. Two researchers screened the literature and extracted relevant data. Newcastle-Ottawa Scale (NOS) was used to evaluate quality of the literature and RevMan 5.3 software was used for meta-analysis.Results:A total of 30 studies were included. Meta-analysis results showed that smoking [ OR=3.76, 95% confidence interval ( CI) : 2.43-5.82, P<0.01], diabetes ( OR=2.95, 95% CI: 2.15-4.06, P<0.01) , hypertension ( OR=2.55, 95% CI: 1.50-4.34, P=0.006) , hyperlipidemia ( OR=7.12, 95% CI: 3.46-14.68, P<0.01) , coronary heart disease ( OR=3.06, 95% CI: 1.10-8.47, P=0.03) , homocysteine ( OR=2.36, 95% CI: 1.30-4.27, P=0.005) , clopidogrel drug-related gene ( CYP2C19) mutation ( OR=3.04, 95% CI: 1.63-5.68, P=0.005) , lesion vessel diameter ( OR=3.43, 95% CI: 1.30-9.05, P=0.01) , residual stenosis ( OR=6.08, 95% CI: 3.28-14.07, P<0.01) ) , stent type ( OR=2.26, 95% CI: 1.18-4.36, P=0.01) , stent length ( OR=3.52, 95% CI: 2.34-5.30, P<0.01) were associated with ISR after VAS operation in patients with ischemic cerebrovascular disease. Conclusions:Postoperative smoking, history of diabetes mellitus, history of hypertension, history of hyperlipidemia, history of coronary heart disease, high level of homocysteine, CYP2C19 mutation, shorter lesion vessel diameter, postoperative residual stenosis, use of bare metal stents and longer stent length are risk factors for ISR after VAS in patients with ischemic cerebrovascular disease. Clinical medical staff should adjust the follow-up time of postoperative patients according to risk factors and formulate individualized strategies to prevent the occurrence of ISR.

Objective Vertigo is the main clinical feature and cerebral atherosclerosis is the major etiological factor and pathogenesy of posterior circulation ischemia (PCIV).The objective of this study was to observe the clinical effect of butylphthalide combined with naloxone on PCIV and hemodynamics . Methods One hundred and sixty two patients with PCIV were classified into treatment group and control group .In the treatment group , butylphthalide soft capsules were administrated by oral and naloxone 2.4 mg were administrated by intravenous drip per day .In the control group , Xueshuantong at the dose of 300 mg was given by intravenous drip per day.All the treatment lasted for 14 days.Transcranial doppler (TCD) examination was performed for all patients before and after the treatment.The mean velocity (Vm) and the systolic velocity (Vs) of bilateral vertebral arteries were recorded .Clinical cure rate was evaluated . Results Basilar artery Vm and Vs increased after treatment in the control group compared with those before treatment ([30.15 ±3.84])cm/s vs ([26.95 ±3.72])cm/s, ([40.87 ±4.54])cm/s vs ([37.16 ±4.72])cm/s.Basilar artery Vm and Vs increased after treatment compared with before treatment in the treatment group ([34.47 ±3.53]) cm/s vs ([27.53 ± 3.68])cm/s, ([42.25 ±5.29])cm/s vs ([35.87 ±4.85])cm/s, (P<0.05).Basilar artery Vm and Vs increased in the treatment group compared with the control group after the treatment ([34.47 ±3.53])cm/s vs ([30.15 ±3.84])cm/s, ([42.25 ±5.29])cm/s vs ([40.87 ±4.54])cm/s, (P<0.05).The cure rate and total effective rate in the treatment group (58.8%, 93.8%) were higher than thoes in the control group, respectively (31.7%, 75.6%)(P<0.05). Conclusion Butylphthalide soft capsules combined with naloxone have definite clinical curative effect and few side for PCIV treatment.