Objective: To investigate the differences in the proportions of BMPR2 mutations in familial hereditary pulmonary arterial hypertension (HPAH) and idiopathic pulmonary arterial hypertension (IPAH) between males and females and the relationship between BMPR2 mutation and PAH severity.Methods: A computer was used to search the electronic Cochrane Library, PubMed/MEDLINE, and EMBASE databases for clinical trials containing information on the relationship between PAH prognosis and BMPR2 mutations through March 2019. After obtaining the data, a meta-analysis was performed using Review Manager Version 5.3 and Stata.Results: A meta-analysis was performed on 17 clinical trials (2198 total patients: 644 male, 1554 female). The results showed that among patients with HPAH and IPAH, the BMPR2 mutation rate is higher in male than in female patients [male group (224/644, 34.78%), female group (457/1554, 29.41%), OR = 1.30, 95% CI: 1.06~1.60,P = 0.01, I² = 10%]. Furthermore, haemodynamic and functional parameters were more severe in IPAH and HPAH patients with BMPR2 mutations than in those without, and those with BMPR2 mutation were diagnosed at a younger age. The risk of death or transplantation was higher in PAH patients with BMPR2 mutations than in those without (OR = 2.51, 95% CI: 1.29~3.57,P = 0.003, I² = 24%). Furthermore, the difference was significant only in male patients (OR = 5.58, 95% CI: 2.16~14.39,P = 0.0004, I² = 0%) and not in female patients (OR = 1.41, 95% CI: 0.75~2.67,P = 0.29, I² = 0%).Conclusion: Among patients with HPAH and IPAH, men are more likely to have BMPR2 mutations, which may predict more severe PAH indications and prognosis.

Lung cancer has high incidence and mortality rates, and lung squamous cell carcinoma (LUSC) is a common form of non‑small‑cell lung carcinoma (NSCLC). The aim of our study was to discover long non‑coding RNAs (lncRNAs) associated with LUSC prognosis. RNA‑sequencing data obtained from LUSC samples were extracted from The Cancer Genome Atlas database. Using the limma package, differentially expressed genes (DEGs; including differentially expressed lncRNA genes (DELs), coding genes (DECs), and other genes (DEOs) ) between LUSC and control samples were analyzed. Using Kaplan‑Meier survival analysis, prognosis‑associated lncRNAs were further selected. Following the calculation of Pearson's correlation coefficients between DELs and other DEGs, the DEL‑DEG co‑expression network was visualized using Cytoscape software. Using the clusterProfiler package, potential functions for DECs co‑expressed with DELs were predicted. There were 1,305 DEGs in LUSC samples, including 153 DELs, 1,109 DECs, and 43 DEOs. Based on survival analysis, 22 prognosis‑associated lncRNAs (including surfactant associated 1, pseudogene (SFTA1P), long intergenic non‑protein coding RNA 968 (LINC00968), GATA6 antisense RNA 1, (GATA6‑AS1) TBX5 antisense RNA 1 (TBX5‑AS1) and FEZF1 antisense RNA 1 (FEZF1‑AS1)) in LUSC were selected from these DELs, and the associated abnormal expression levels were also verified in LUSC clinical samples. A DEL‑DEG co‑expression network was constructed, which involved 93 DELs. Co‑expressed DECs were enriched for only 8 prognosis‑associated DELs, including LINC00968, SFTA1P, and TBX5‑AS1. Specifically, mitogen‑activated protein kinase (MAPK) signaling pathway‑associated genes were enriched in DECs co‑expressed with LINC00968, SFTA1P, GATA6‑AS1, TBX5‑AS1 and FEZF1‑AS1, which may be prognosis‑associated lncRNAs in LUSC. In addition, LINC00968 may affect the outcome of patients with LUSC via the MAPK signaling pathway.

Cardiac fibrosis is a hallmark of cardiac remodeling associated with nearly all forms of heart disease. Clinically, no effective therapeutic drugs aim to inhibit cardiac fibrosis, owing to the complex etiological heterogeneity and pathogenesis of this disease. A two‑in‑one protein structure, a ubiquitous expression profile and unique biophysical characteristics enable the involvement of transient receptor potential melastatin‑subfamily member 7 (TRPM7) in the pathogenesis and development of fibrosis‑related cardiac diseases, such as heart failure (HF), cardiomyopathies, arrhythmia and hyperaldosteronism. In response to a variety of stimuli, multiple bioactive molecules can activate TRPM7 and related signaling pathways, leading to fibroblast proliferation, differentiation and extracellular matrix production in cardiac fibroblasts. TRPM7‑mediated Ca²⁺ signaling and TGF‑β1 signaling pathways are critical for the formation of fibrosis. Accumulating evidence has demonstrated that TRPM7 is a potential pharmacological target for halting the development of fibrotic cardiac diseases. Reliable drug‑like molecules for further development of high‑affinity in vivo drugs targeting TRPM7 are urgently needed. The present review discusses the widespread and significant role of TRPM7 in cardiac fibrosis and focuses on its potential as a therapeutic target for alleviating heart fibrogenesis.

Pulmonary hypertension (PH) is occult, with no distinctive clinical manifestations and a poor prognosis. Pulmonary vascular remodelling is an important pathological feature in which pulmonary artery smooth muscle cells (PASMCs) phenotypic switching plays a crucial role. MicroRNAs (miRNAs) are a class of evolutionarily highly conserved single‐stranded small noncoding RNAs. An increasing number of studies have shown that miRNAs play an important role in the occurrence and development of PH by regulating PASMCs phenotypic switching, which is expected to be a potential target for the prevention and treatment of PH. miRNAs such as miR‐221, miR‐15b, miR‐96, miR‐24, miR‐23a, miR‐9, miR‐214, and miR‐20a can promote PASMCs phenotypic switching, while such as miR‐21, miR‐132, miR‐449, miR‐206, miR‐124, miR‐30c, miR‐140, and the miR‐17~92 cluster can inhibit it. The article reviews the research progress on growth factor‐related miRNAs and hypoxia‐related miRNAs that mediate PASMCs phenotypic switching in PH.

Background: Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality rates, and the efficiency of current HPH treatment strategies is unsatisfactory. Endothelial-to-mesenchymal transition (EndMT) in the pulmonary artery plays a crucial role in HPH. Previous studies have shown that lncRNA-H19 (H19) is involved in many cardiovascular diseases by regulating cell proliferation and differentiation but the role of H19 in EndMT in HPH has not been defined. Methods: In this research, the expression of H19 was investigated in PAH human patients and rat models. Then, we established a hypoxia-induced HPH rat model to evaluate H19 function in HPH by Echocardiography and hemodynamic measurements. Moreover, luciferase reporter gene detection, and western blotting were used to explore the mechanism of H19. Results: Here, we first found that the expression of H19 was significantly increased in the endodermis of pulmonary arteries and that H19 deficiency obviously ameliorated pulmonary vascular remodelling and right heart failure in HPH rats, and these effects were associated with inhibition of EndMT. Moreover, an analysis of luciferase activity indicated that microRNA-let-7 g (let-7 g) was a direct target of H19. H19 deficiency or let-7 g overexpression can markedly downregulate the expression of TGFβR1, a novel target gene of let-7 g. Furthermore, inhibition of TGFβR1 induced similar effects to H19 deficiency. Conclusions: In summary, our findings demonstrate that the H19/let-7 g/TGFβR1 axis is crucial in the pathogenesis of HPH by stimulating EndMT. Our study may provide new ideas for further research on HPH therapy in the near future.