MicroRNA-27b-3p down-regulates FGF1 and aggravates pathological cardiac remodelling.

AIMS: The heart undergoes pathological remodelling under increased stress and neuronal imbalance. MicroRNAs (miRNAs) are involved in post-transcriptional regulation of genes in cardiac physiology and pathology. However, the mechanisms underlying miRNA-mediated regulation of pathological cardiac remodelling remain to be studied. This study aimed to explore the function of endogenous microRNA-27b-3p (miR-27b-3p) in pathological cardiac remodelling. METHODS AND RESULTS: miR-27b-3p expression was elevated in the heart of a transverse aortic constriction (TAC)-induced cardiac hypertrophy mouse model. miR-27b-knockout mice showed significantly attenuated cardiac hypertrophy, fibrosis, and inflammation induced by two independent pathological cardiac hypertrophy models, TAC and Angiotensin II (Ang II) perfusion. Transcriptome sequencing analysis revealed that miR-27b deletion significantly down-regulated TAC-induced cardiac hypertrophy, fibrosis, and inflammatory genes. We identified fibroblast growth factor 1 (FGF1) as a miR-27b-3p target gene in the heart which was up-regulated in miR-27b-null mice. We found that both recombinant FGF1 (rFGF1) and inhibition of miR-27b-3p enhanced mitochondrial oxidative phosphorylation (OXPHOS) and inhibited cardiomyocyte hypertrophy. Importantly, rFGF1 administration inhibited cardiac hypertrophy and fibrosis in TAC- or Ang II-induced models and enhanced OXPHOS by activating PGC1α/ß. CONCLUSIONS: Our study demonstrated that miR-27b-3p induces pathological cardiac remodelling and suggests that inhibition of endogenous miR-27b-3p or administration of FGF1 might have the potential to suppress cardiac remodelling in a clinical setting.

Application of 3D printing in the surgical planning of hypertrophic obstructive cardiomyopathy and physician-patient communication: a preliminary study.

BACKGROUND: The aim of this study was to evaluate the effect of 3-dimensional (3D) printing in treatment of hypertrophic obstructive cardiomyopathy (HOCM) and its roles in doctor-patient communication. METHODS: 3D-printed models were constructed preoperatively and postoperatively in seven HOCM patients received surgical treatment. Based on multi-slice computed tomography (CT) images, regions of disorder were segmented using the Mimics 19.0 software (Materialise, Leuven, Belgium). After generating an STL-file (StereoLithography file) with patients' data, the 3D printer (Objet350 Connex3, Stratasys Ltd., USA) created a 3D model. The pre- and post-operative 3D-printed models were used to make the surgical plan preoperatively and evaluate the outcome postoperatively. Meanwhile, a questionnaire was designed for patients and their relatives to learn the effectiveness of the 3D-printed prototypes in the preoperative conversations. RESULTS: The heart anatomies were accurately printed with 3D technology. The 3D-printed prototypes were useful for preoperative evaluation, surgical planning, and practice. Preoperative and postoperative echocardiographic evaluation showed left ventricular outflow tract (LVOT) obstruction was adequately relieved (82.71±31.63 to 14.91±6.89 mmHg, P<0.001), the septal thickness was reduced from 21.57±4.65 to 17.42±5.88 mm (P<0.001), and the SAM disappeared completely after the operation. Patients highly appreciated the role of 3D model in preoperative conversations and the communication score was 9.11±0.38 points. CONCLUSIONS: A 3D-printed model is a useful tool in individualized planning for myectomies and represent a useful tool for physician-patient communication.

Comparison of Clinical Effects between Percutaneous Transluminal Septal Myocardial Ablation and Modified Morrow Septal Myectomy on Patients with Hypertrophic Cardiomyopathy.

BACKGROUND: Percutaneous transluminal septal myocardial ablation (PTSMA) and modified Morrow septal myectomy (MMSM) are two invasive strategies used to relieve obstruction in patients with hypertrophic cardiomyopathy (HCM). This study aimed to determine the clinical outcome of these two strategies. METHODS: From January 2011 to January 2015, 226 patients with HCM were treated, 68 by PTSMA and 158 by MMSM. Both ultrasonic cardiograms and heart functional class were recorded before, after operations and in the follow-up. Categorical variables were compared using Chi-square or Fisher's exact tests. Quantitative variables were compared using the paired samples t-test. RESULTS: Interventricular septal thickness was significantly reduced in both groups (21.27 ± 4.43 mm vs. 18.72 ± 4.13 mm for PTSMA, t = 3.469, P < 0.001, and 21.83 ± 5.03 mm vs. 16.57 ± 3.95 mm for MMSM, t = 10.349, P < 0.001, respectively). The left ventricular outflow tract (LVOT) pressure gradient (PG) significantly decreased after the operations in two groups (70.30 ± 44.79 mmHg vs. 39.78 ± 22.07 mmHg for PTSMA, t = 5.041, P < 0.001, and 74.58 ± 45.52 mmHg vs. 13.95 ± 9.94 mmHg for MMSM, t = 16.357, P < 0.001, respectively). Seven patients (10.29%) in the PTSMA group required a repeat operation in the follow-up. Eight (11.76%) patients were evaluated for New York Heart Association (NYHA) III/IV in the PTSMA group, which was significantly more than the five (3.16%) in the same NYHA classes for the MMSM group at follow-up. Less than 15% of patients in the PTSMA group and none of the patients in the MMSM group complained of chest pain during follow-up. CONCLUSIONS: Both strategies can not only relieve LVOT PG but also improve heart function in patients with HCM. However, MMSM might provide a more reliable reduction in gradients compared to PTSMA.

Choledochojejunostomy with an innovative magnetic compressive anastomosis: How to determine optimal pressure?

AIM: To investigate the optimal magnetic pressure and provide a theoretical basis for choledochojejunostomy magnetic compressive anastomosis (magnamosis). METHODS: Four groups of neodymium-iron-boron magnets with different magnetic pressures of 0.1, 0.2, 0.3 and 0.4 MPa were used to complete the choledochojejunostomy magnamosis. Twenty-six young mongrel dogs were randomly divided into five groups: four groups with different magnetic pressures and 1 group with a hand-suture anastomosis. Serum bilirubin levels were measured in all groups before and 1 wk, 2 wk, 3 wk, 1 mo and 3 mo after surgery. Daily abdominal X-ray fluoroscopy was carried out postoperatively to detect the path and the excretion of the magnet. The animals were euthanized at 1 or 3 mo after the operation, the burst pressure was detected in each anastomosis, and the gross appearance and histology were compared according to the observation. RESULTS: The surgical procedures were all successfully performed in animals. However, animals of group D (magnetic pressure of 0.4 MPa) all experienced complications with bile leakage (4/4), whereas half of animals in group A (magnetic pressure of 0.1 MPa) experienced complications (3/6), 1 animal in the manual group E developed anastomotic stenosis, and animals in group B and group C (magnetic pressure of 0.2 MPa and 0.3 MPa, respectively) all healed well without complications. These results also suggested that the time required to form the stoma was inversely proportional to the magnetic pressure; however, the burst pressure of group A was smaller than those of the other groups at 1 mo (187.5 ± 17.7 vs 290 ± 10/296.7 ± 5.7/287.5 ± 3.5, P < 0.05); the remaining groups did not differ significantly. A histologic examination demonstrated obvious differences between the magnamosis groups and the hand-sewn group. CONCLUSION: We proved that the optimal range for choledochojejunostomy magnamosis is 0.2 MPa to 0.3 MPa, which will help to improve the clinical application of this technique in the future.