In this study, we used three-dimensional (3D) printing to prepare a template of a microfluidic chip from which a polydimethylsiloxane (PDMS)lung chip was successfully constructed. The upper and lower channels of the chip are separated by a microporous membrane. The upper channel is seeded with lung cancer cells, and the lower channel is seeded with vascular endothelial cells and continuously perfused with cell culture medium. This lung chip can simulate the microenvironment of lung tissue and realize the coculture of two kinds of cells at different levels. We used a two-dimensional (2D) well plate and a 3D lung chip to evaluate the effects of different EGFR-targeting drugs (gefitinib, afatinib, and osimertinib) on tumor cells. The 3D lung chip was superior to the 2D well plate at evaluating the effect of drugs on the NCI-H650, and the results were more consistent with existing clinical data. For primary tumor cells, 3D lung chips have more advantages because they simulate conditions that are more similar to the physiological cell microenvironment. The evaluation of EGFR-targeted drugs on lung chips is of great significance for personalized diagnosis and treatment and pharmacodynamic evaluation.

Drug resistance to irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a primary factor affecting their therapeutic efficacy in human non-small cell lung cancer (NSCLC). NSCLC cells can undergo epithelial-mesenchymal transition (EMT) induced by many factors in the tumour microenvironment (TME), which plays a crucial role in tumour drug resistance. In this study, a multicellular lung-on-a-chip that can realise the cell co-culture of the human non-small cell lung cancer cell line HCC827, human foetal lung fibroblasts (HFL-1), and human umbilical vein endothelial cells (HUVECs) is prepared. The TME was simulated on the chip combined with perfusion and other factors, and the drug evaluation of osimertinib was performed to explore the drug resistance mechanism of EGFR-TKIs. In the early stages, a two-dimensional static cell co-culture was achieved by microchip, and the results showed that HFL-1 cells could be transformed into cancer-associated fibroblasts (CAFs), and HCC827 cells could undergo EMT, both of which were mediated by Interleukin-6 (IL-6). Vimentin (VIM) and Alpha Skeletal Muscle Actin (a-SMA) expression of HFL-1 was upregulated, whereas E-cadherin (E-cad) expression of HCC827 was down-regulated. Further, N-cadherin (N-cad) expression of HCC827 was upregulated. In both the static cell co-culture and multicellular lung-on-a-chip, HCC827 cells with CAFs co-culture or IL-6 treatment developed resistance to osimertinib. Further use of the IL-6 antibody inhibitor tocilizumab could reverse EGFR-TKI resistance to a certain extent. Combination therapy with tocilizumab and EGFR-TKIs may provide a novel therapeutic strategy for overcoming EGFR-TKI resistance caused by EMT in NSCLC. Furthermore, the lung-on-a-chip can simulate complex TME and can be used for evaluating tumour resistance and exploring mechanisms, with the potential to become an important tool for personalised diagnosis, treatment, and biomedical research.

Background: Certain pregnant women suffer from cardiac pathology,and a few of them need cardiac operations under cardiopulmonary bypass during pregnancy. Feto-neonatal and maternal outcomes have not been sufficiently described. Methods: We conducted a retrospective review of 22 cases of women undergoing cardiac operations under cardiopulmonary bypass during pregnancy in our hospital from Jan.2014 to Mar.2019. Results: All 22 patients were alive after treatment. The types of cardiac disorders included congenital heart defects, rheumatic heart disease,infective endocarditis,aortic dissection, obstruction and/or thrombosis of a prosthetic valve. Only one case was a twin pregnancy,and the other 21 cases were singletons. Four fetuses died in the utero after surgery. Three patients chose termination of the pregnancy after the cardiac operations: one fetus was detected abnormity of the brain and the other two patients abandoned pregnancy. Fourteen fetuses were alive and born without any abnormity. Two fetuses suffered from neonatal intracranial hemorrhage and died after birth. Conclusions: Cardiac operation under cardiopulmonary bypass during pregnancy is a challenge for physicians in multidisciplinary teams. Strictly evaluating the indication is vital. On the other hand, some patients can benefit from this management.

Purpose: To investigate the influence and possible pathophysiological mechanism of pulsatile cardiopulmonary bypass (CPB) in various frequencies in pediatric patients undergoing congenital cardiac surgery. Patients and methods: Clinical data and hemodynamic parameters were collected in 80 patients who underwent congenital cardiac surgeries and were perfused in different settings: pulsatile perfusion (PP) in frequencies of 30 beats/min, PP 60 beats/min, PP 100 beats/min and non-pulsatile perfusion (NP). Serum proteins, plasma-free hemoglobin (PFH), endothelin-1 (ET-1) and nitric oxide (NO) were collected to study possible pathophysiological changes, possible hematological injury and oxidative status under different perfusing conditions. Results: Patients in all groups had similar baseline characteristics, aortic cross-clamping time and CPB duration. More effective pulse gradient (PG), energy-equivalent pressure (EEP) and surplus hemodynamic energy (SHE) were observed in pulsatility with lower frequency setting, under which more patients achieved physiologically normal mean arterial pressure (MAP), without the support of inotropic agents during bypass. Significant between-group differences of serum proteins and PFH were absent the whole time during and after bypass, while a relatively lower percentage of perioperative requirement of diuretics was observed in the low frequency pulsatile group. A better performance to oxidative stress was seen in the low frequency group with higher levels of NO and lower concentration of ET-1, and both intergroup differences were found (P<0.01). Satisfactory clinical outcome was obtained on post procedure course in all groups. Conclusion: Pulsatile perfusion with low frequency setting in pediatric patients undergoing congenital cardiac surgery showed better hemodynamic profiles, potential protective effects on vital organs, better oxidative status and satisfactory clinical outcome.

Objectives: Transcatheter closure (TCC) and surgical closure (SC) are the two main approaches for congenital coronary artery fistula (CCAF), but data on the comparisons of the efficacy and safety of these two approaches are limited. Methods: We retrospectively reviewed pediatric patients with CCAF in Guangdong Cardiovascular Institute between January 2002 and December 2017. Patients who were qualified into our criteria were included into final analysis. The rate of successful closure and complications during hospitalization and at follow-up were compared between SC and TCC groups. Results: In total, 121 pediatric patients (male, n = 69; female, n = 52) with CCAF were divided to TCC (n = 63) and SC groups (n = 58) according to the indications. The mean age was 5.3 ± 1.4 years. The baseline characteristics of these two groups were similar except for the fistula anatomic feature. After adjusted for the fistula anatomy, compared to SC, TCC was associated with higher risk of major complications (p = 0.013). Proportions of patients requiring blood transfusion and intra-operative blood loss were higher in SC versus TCC groups, as were longer duration of hospital and ICU stay during hospitalization. In contrast, myocardial ischemia (10.2% vs 0.0%, p = 0.028), residual shunts (16.9% vs 3.6%, p = 0.045) and new-onset moderate-to-severe valve regurgitation (11.9% vs 0.0%, p = 0.013) were higher in TCC group versus SC groups during follow-up. Conclusions: TCC has less invasive and faster recovery. However, SC had a higher successful rate and lower risk of major complications in pediatric patients.

The objective of this study was to compare the effects of different shunt diameters and pulmonary artery (PA) stenosis grades on the hemodynamics of central shunts to determine an optimal surgical plan and improve the long-term outcomes of the operation. A 3D anatomical model was reconstructed based on the patient’s clinical CT data. 3D computational fluid dynamics models were built with varying degrees of stenosis (the stenosis ratio α was represented by the ratio of blood flow through the main pulmonary artery to cardiac output, ranging from 0 to 30%; the smaller the value of α, the more severe the pulmonary artery stenosis) and varying shunt diameters (3, 3.5, 4, 4.5, and 5 mm). Our results show that the asymmetry of pulmonary artery flow increased with increasing shunt diameter and α, which will be more conducive to the development of the left pulmonary artery. Additionally, the pulmonary-to-systemic flow ratio (Q_P/Q_S) increases with the shunt diameter and α, and all the values exceed 1. When the shunt diameter is 3 mm and α = 0%, Q_P/Q_S reaches the minimum value of 1.01, and the oxygen delivery reaches the maximum value of 205.19 ml/min. However, increasing shunt diameter and α is beneficial to reduced power loss and smoother PA flow. In short, for patients with severe PA stenosis (α is small), a larger-diameter shunt may be preferred. Conversely, when the degree of PA stenosis is moderate, a smaller shunt diameter can be considered.