[Postpartum fatal pulmonary embolism with F5 gene mutation: a case report].

Pulmonary embolism (PE) is one of the leading causes of maternal death. Various clinical and environmental risk factors can cause PE. Here, we reported an uncommon PE case with multiple etiological causes, including caesarean section, overweight, anti-cardiolipin antibody positive, and factor 5 gene mutation. The patient was a 25-year-old woman who developed cardiac asystole and apnea one day after cesarean delivery due to pulmonary embolism. After cardiopulmonary resuscitation and thrombolytic therapy, high doses of epinephrine were still needed to maintain blood pressure and heart rate, so we treated her with venoarterial extracorporeal membrane oxygenation (ECMO) to maintain systemic circulation. She progressively improved and was discharged on oral warfarin treatment. Comprehensive laboratory tests revealed a positive anticardiolipin antibody. Through whole exon gene sequencing, we identified a novel mutation (A2032➝G) in the F5 gene. This mutation was predicted to result in the replacement of lysine with glutamate at position 678, close to one of the APC cleavage sites. P.Lys678Glu was found to be a detrimental mutation by SIFT software and suspected detrimental by Polyphen-2 software. Attention should be paid to the etiological screening of young patients with pulmonary embolism, which is helpful in guiding the anticoagulant scheme and anticoagulant duration, and is of great significance in preventing thrombosis recurrence and complications.

Overexpression of ACE2 prevents hypoxia-induced pulmonary hypertension in rats by inhibiting proliferation and immigration of PASMCs.

OBJECTIVE: Imbalance of the ratio of angiotensin converting enzyme (ACE) and ACE2 may lead to pathological conditions in lung. However, its effect on hypoxia-induced pulmonary hypertension (HPH) remains unclear. Therefore, the aim of this study was to investigate the effects of ACE2 overexpression on rat primary pulmonary arterial smooth muscle cells (PASMCs) and HPH rat model. MATERIALS AND METHODS: ACE and ACE2 expression in rat PASMCs under hypoxia condition, as well as in HPH rat model, was detected. The overexpressed ACE2 gene was transfected into PASMCs by Lentiviral. Later, the proliferation and migration of PASMCs were evaluated. Meanwhile, the overexpressed ACE2 gene was transfected into rats and exposed to hypoxia for four weeks. Finally, the right ventricular systolic pressure, the right ventricular hypertrophy, and the percentage of the medial wall thickness were measured to evaluate the development of HPH. RESULTS: Imbalance of the expression of ACE/ACE2 was indicated in rat PASMCs under hypoxia condition and in the HPH rat model, respectively. The overexpression of ACE2 significantly inhibited PASMCs proliferation and migration. Moreover, the overexpressed ACE2 could significantly attenuate pulmonary hypertension, pulmonary vascular remodeling, and right ventricular hypertrophy in HPH rat model. CONCLUSIONS: ACE2 is related to the formation of pulmonary vascular remodeling and pulmonary hypertension. Furthermore, it may prevent hypoxia-induced pulmonary hypertension by inhibiting the proliferation of PASMCs.

Effect evaluation of cisplatin-gemcitabine combination chemotherapy for advanced non-small cell lung cancer patients using microarray data.

OBJECTIVE: This study was performed to evaluate the therapeutic effect of cisplatin-gemcitabine combination chemotherapy for advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Dataset GSE39345 from patients who underwent cisplatin-gemcitabine combination chemotherapy and normal controls was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using Limma package and divided into 3 datasets: unique DEGs in NSCLC before chemotherapy vs. control samples (dataset A), common DEGs (dataset B), unique DEGs in NSCLC after chemotherapy vs. control samples (dataset C). Enrichment analysis was to identify functions or pathways of DEGs. Protein-protein interaction (PPI) analysis was to identify hub nodes and interacting pairs in dataset C and constructed into PPI network using Cytoscape software, followed by screening of small molecules using Connectivity Map. RESULTS: Herein, 230 unique DEGs in dataset A, 584 common DEGs in dataset B and 1562 unique DEGs in dataset C were obtained. The 230 DEGs were significantly enriched in methylation and positive regulation of cell differentiation; the 584 DEGs were significantly enriched in positive regulation of cell differentiation and cytokine-cytokine receptor interaction pathway; the 1562 DEGs were enriched in functions associated with defense response. RELA and PLCB3 correlated with PLCE1 and INADL were hub nodes in the PPI network. Cefoperazone was the small molecule negatively correlated with DEGs. CONCLUSIONS: Chemotherapy could prevent genes from aberrant methylation, partially restore cell differentiation process, fail to regulate cytokine-cytokine receptor interaction and induce weakened defense response. Cefoperazone could be used as a supplementary drug.