The study aimed to investigate the relationship between heart-carotid pulse transit time and carotid intima-media thickness (CIMT) in hypertensive patients, and whether including the pre-ejection period (PEP) in heart-carotid pulse transit time would affect this correlation. A total of 62 hypertensive patients were included in this study. They were divided into the normal CIMT group (n=33, CIMT⩽0.8 mm) and the thickened CIMT group (n=29, CIMT>0.8 mm). The noninvasive ultrasound method was used to measure CIMT, electrocardiogram R-wave-based heart-carotid pulse transit time (rcPTT) and PEP. Aortic valve-carotid artery pulse transit time (acPTT) was calculated by subtracting PEP from rcPTT. Simple linear analysis showed that CIMT was negatively associated with rcPTT and acPTT (r=-0.57, P<0.0001; r=-0.41, P=0.016) in the normal CIMT group as well as in the thickened CIMT group (r=-0.50, P=0.0053; r=-0.59, P=0.001). These relationships were eliminated in the normal CIMT group after adjusting for age, gender, smoking behaviour, systolic blood pressure, diastolic blood pressure and cholesterol levels. However, rcPTT and acPTT still showed significant correlations with CIMT in the thickened CIMT group. In conclusion, rcPTT and acPTT were associated with CIMT, independent of well-known clinical confounders in thickened CIMT hypertensive patients. Therefore, rcPTT and acPTT might be useful markers for atherosclerosis evaluation.

Summary statement8 Box-Behnken model is an efficient method to optimized process conditions of 9 microencapsules strength for long-term cell culture, promotes CHO cells viability and 10 protein production in a stirred tank bioreactor.11 not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/165464 doi: bioRxiv preprint first posted online Jul. 19, 2017; 2 ABSTRACT: Cell microencapsulation technology has been proved to be a valuable 1 technology in the fields of large-scale cell culture. It is important to accurately construct the 2 microcapsule membranes with desired properties including a certain thickness suitable for cell 3 growth, and maximum strength for the stability of microencapsules. As single factor 4 experiments are time-consuming to obtain the desired membrane preparation conditions, 5 Box-Behnken model was used to investigate the interactions among reaction conditions, 6 predict the optimized reaction conditions for given purpose, that was membrane with 7 maximum strength and desired thickness for microencapsulated cell culture. Significant values 8 of R 2 in this study indicated the model theoretical values are very close to the measured values. 9 Based on the desired membrane thickness, the process of maximum strength was optimized, 10 and the prediction agreement of measured value and model theoretical value was 91.11%. 11The optimized microencapsules with maximum strength and 15 μm membrane thickness 12 promote CHO cells viability and protein production in stirred tank bioreactor. The result 13 shows that Box-Behnken model is an efficient method to optimized process conditions of 14 microencapsules strength for long-term cell culture. 15