Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease characterized by the excessive accumulation of activated myofibroblasts that deposit extracellular matrix (ECM) protein, leading to progressive scar formation and mechanical stress. However, the cellular origin and fate of myofibroblasts remain controversial, and the mechanisms by which myofibroblasts sense mechanical cues in the lung are unclear. Here, we report that periostin (Postn) is a reliable and distinctive marker for pulmonary myofibroblasts, while ablation of Postn ⁺ myofibroblasts after injury ameliorated lung fibrosis. PIEZO1 was highly expressed in Postn ⁺ myofibroblast and played a vital role in mechanoactivation of Postn ⁺ myofibroblast and development of lung fibrosis. Conditional deletion of Piezo1 in Postn ⁺ myofibroblasts significantly inhibited lung fibrosis by suppressing myofibroblast activation and proliferation. Loss of Piezo1 led to disruption of actin organization and prevention of Yap/Taz nuclear localization, thus shifting the myofibroblasts from a proliferative state into a stressed and apoptotic state. Furthermore, myofibroblast-specific Yap/Taz deletion fully recapitulated the protective phenotypes of myofibroblast- Piezo1 –KO mice. These findings show that periostin marks pulmonary myofibroblasts, and that PIEZO1-mediated mechanosensation is essential for myofibroblast activation in the lung. Targeting PIEZO1 in the periostin-expressing cells is a novel therapeutic option to interfere with fibrotic diseases such as IPF .

The present study is aimed at investigating the molecular mechanism of C1q/TNF-related protein 9 (CTRP9) and providing a new perspective in arteriovenous shunt-induced pulmonary arterial hypertension (PAH). PAH was established by an arteriovenous shunt placement performed in rats. Adenovirus(Ad)-CTRP9 and Ad-green fluorescent protein viral particles were injected into the rats through the tail vein. Following 12 weeks, the mean pulmonary arterial pressure (mPAP) and right ventricular systolic pressure (RVSP) were measured and morphological analysis was conducted to confirm the establishment of the PAH model. The systemic elevation of CTRP9 maintained pulmonary vascular homeostasis and protected the rats from dysfunctional and abnormal remodeling. CTRP9 attenuated the pulmonary vascular remodeling in the shunt group by decreasing the mPAP and RVSP, which was associated with suppressed inflammation, apoptosis, and extracellular matrix injury. In addition, CTRP9 dramatically increased the phosphorylation of AKT and p38-MAPK in the lung tissues of shunt-operated animals. These findings suggest a previously unrecognized effect of CTRP9 in pulmonary vascular homeostasis during PAH pathogenesis.

The correlation between cerebral small vessel disease (CSVD) and the outcomes of acute ischemic stroke (AIS) patients after endovascular therapy (EVT) remains elusive. We aimed to investigate the effect of combined white matter hyperintensities (WMH) and enlarged perivascular spaces (EPVS) as detected in magnetic resonance imaging (MRI) at baseline on clinical outcomes in patients with AIS who underwent EVT. AIS patients that experienced EVT were retrospectively analyzed in this single-center study. Using MRIs taken prior to EVT, we rated WMH and EPVS as the burden of CSVD and dichotomized the population into two groups: absent-to-moderate and severe. Neurological outcome was assessed at day 90 with a modified Rankin Scale (mRS). Symptomatic intracerebral hemorrhage (sICH), early neurological deterioration (END), malignant cerebral edema (MCE), and hospital death were secondary outcomes. Of the 100 patients (64.0% male; mean age 63.71 ± 11.79 years), periventricular WMHs (28%), deep WMHs (41%), EPVS in basal ganglia (53%), and EPVS in centrum semiovale (73%) were observed. In addition, 69% had an absent-to-moderate total CSVD burden and 31.0% had a severe burden. The severe CSVD was not substantially linked to either the primary or secondary outcomes. Patients with AIS who underwent EVT had an elevated risk (OR: 7.89, 95% CI: 1.0, 62.53) of END if they also had EPVS. When considering WMH and EPVS together as a CSVD burden, there seemed to be no correlation between severe CSVD burden and sICH, END, or MCE following EVT for AIS patients. Further studies are warranted to clarify the relationship between CSVD burden and the occurrence, progression, and prognosis of AIS.

Background: Inflammation significantly impacts chronic kidney disease (CKD) and acute myocardial infarction (AMI). This study investigates the prognostic value of inflammatory markers in predicting outcomes for CKD patients with AMI.Methods: We enrolled patients diagnosed with CKD concomitant with AMI, choosing five inflammatory markers related to both diseases. Patients were categorized into elevated inflammatory markers group and control group based on inflammatory markers cut-off values for predicting in-hospital major adverse cardiac and cerebrovascular events (MACCE). Using univariate and multivariate logistic regression, we identified inflammation-related risk factors for MACCE. We adjusted covariates stepwise to explore the relationship between independent risk factors and adverse outcomes. We also evaluated the predictive value of these markers for MACCE by receiver operating characteristic (ROC) curves.Results: In the multivariate logistic regression analysis, higher levels of neutrophil-to-lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) significantly increased risk of MACCE (all P < 0.05). After adjusting above two indicators, NLR was independently associated with in-hospital MACCE in CKD patients with AMI (OR = 10.764, 95% CI: 1.887–61.406, P = 0.007). Furthermore, compared to other inflammatory markers, NLR had the highest predictive value for MACCE in patients with AMI and CKD [Area Under the Curve (AUC): 0.748, 95% Confidence Interval (CI): 0.634–0.861, P < 0.001].Conclusion: In CKD patients combined with AMI, elevated levels of inflammation markers could increase the risk of MACCE. NLR may provide superior predictive value compared to other markers.

Background: Arrhythmias are common cardiovascular complications in multiple myeloma (MM) patients and are related to a poor prognosis.Objective: This study aimed to assess the burden of arrhythmias and their prognostic value in patients with MM.Methods: This was a retrospective study of patients with MM between January 2015 and April 2020 at the First Affiliated Hospital of Xi'an Jiaotong University. The incidence of arrhythmia and associated risk factors were evaluated. The relationship between the type of arrhythmia and survival was analyzed.Results: A total of 319 patients with MM were identified, and 48.0% (153/319) had arrhythmias. The most common type of arrhythmia was sinus tachycardia (ST) (15.0%, 48/319), followed by sinus bradycardia (SB) (14.4%, 46/319), premature atrial contractions (PACs) (6.3%, 20/319), conduction disorders (CDs) (6.0%, 19/319), atrial fibrillation (AF) (6.0%, 19/319), premature ventricular contractions (PVCs) (4.4%, 14/319) and paroxysmal supraventricular tachycardia (PSVT) (0.6%, 2/319). The patients with arrhythmias had higher levels of log NT-proBNP and creatinine, greater bortezomib use, and a higher incidence of diabetes than those without arrhythmias (P < 0.05). The all-cause mortality rates of patients without arrhythmias and those with AF, ST, PACs, CDs, SB, and PVCs were 50.6% (84/166), 73.7% (14/19), 60.4% (29/48), 60.0% (12/20), 52.6% (10/19), 34.8% (16/46), and 28.6% (4/14), respectively. In a subgroup analysis of patients experiencing different types of arrhythmias, patients with SB had lower all-cause mortality than patients with AF (P < 0.01). Univariate and multivariate Cox analyses showed that there was a positive statistically significant association between SB and survival (HR: 0.592 [0.352–0.998], P = 0.049) in a subgroup analysis of different arrhythmias.Conclusions: Patients with MM had a heavy arrhythmia burden, and in this study, approximately half of MM patients had arrhythmias. MM patients with SB were associated with lower all-cause mortality than those with AF. SB might be an independent positive factor for prognosis.

Aims: Pulmonary artery smooth muscle cells (PASMCs) sense and respond to constant mechanical strain, which is vital for lung homeostasis and disease. Mechanical stimuli and altered glycolytic metabolism are intrinsically intertwined in proliferative PASMCs undergoing a phenotypic switching, however, it remains unclear how biophysical forces and glycolysis are coupled in PASMCs. We report that PIEZO1 plays a critical role in PASMC metabolism and distinguishable mechanical cues differently rewire PIEZO1-mediated signalling into pro- and anti-glycolytic metabolism. Methods and results: Under hypoxia, activation of PIEZO1 promotes glycolysis in PASMCs through HIF1α and PFKFB3, resulting in profound lactate production and cell proliferation. In severe pulmonary injury induced by bleomycin, PIEZO1 is hyper-activated, which led to PPARγ activation, thereby antagonizing TGFβ signalling and restraining glycolysis and proliferation via FBP1. Loss of smooth muscle Piezo1 attenuates pneumonectomy and hypoxia induced PASMC growth and vascular remodelling, while aggravates pulmonary fibrosis in mice. Conclusion: Our study reveals that PIEZO1-mediated mechano-metabolic coupling contributes to PASMCs plasticity. This discovery identified an intrinsic mechanism that integrates mechanical stretch with cellular glycolysis during pulmonary vascular remodelling.