Non-invasive high frequency oscillatory ventilation inhibiting respiratory motion in healthy volunteers.

Precision radiotherapy needs to manage organ movements to prevent critical organ injury. The purpose of this study is to examine the feasibility of motion control of the lung by suppressing respiratory motion. The non-invasive high frequency oscillatory ventilation (NIHFOV) is a technique commonly used in the protection of lung for patients with acute lung disease. By using a very high respiratory frequency and a low tidal volume, NIHFOV allows gas exchange, maintains a constant mean airway pressure and minimizes the respiratory movements. We tested healthy volunteers NIHFOV to explore the optimal operational parameter setting and the best possible motion suppression achievable. This study was conducted with the approval of Institutional Review Boards of the Wuwei Cancer hospital (approval number: 2021-39) and carried out in accordance with Declaration of Helsinki. The study comprises two parts. Twenty three healthy volunteers participated in the first part of the study. They had 7 sessions of training with the NIHFOV. The duration of uninterrupted, continuous breathing under the NIHFOV and the optimal operational machine settings were defined. Eight healthy volunteers took part in the second part of the study and underwent 4-dimensional CT (4DCT) scanning with and without NIHFOV. Their respiratory waveform under free breathing (FB) and NIHFOV were recorded. The maximum range of motion of the diaphragm from the two scannings was compared, and the variation of bilateral lung volume was obtained to evaluate the impact of NIHFOV technique on lung volume. The following data were collected: comfort score, transcutaneous partial pressure of oxygen (PtcO2), transcutaneous partial pressure of carbon dioxide (PtcCO2), and pulse rate. Data with and without NIHFOV were compared to evaluate its safety, physiological impacts and effect of lung movement suppression. All the volunteers completed the training sessions eventlessly, demonstrating a good tolerability of the procedure. The median NIHFOV-on time was 32 min (22-45 min), and the maximum range of motion in the cephalic-caudal direction was significantly reduced on NIHFOV compared with FB (1.8 ± 0.8 cm vs 0.3 ± 0.1 cm, t = - 3.650, P = 0.003); the median range of motion was only 0.3 ± 0.1 cm on NIHFOV with a good reproducibility. The variation coefficient under NIHFOV of the right lung volume was 2.4% and the left lung volume was 9.2%. The PtcO2 and PtcCO2 were constantly monitored during NIHFOV. The medium PtcCO2 under NIHFOV increased lightly by 4.1 mmHg (interquartile range [IQR], 4-6 mmHg) compared with FB (t = 17.676, P < 0.001). No hypercapnia was found, PtcO2 increased significantly in all volunteers during NIHFOV (t = 25.453, P < 0.001). There was no significant difference in pulse rate between the two data sets (t = 1.257, P = 0.233). NIHFOV is easy to master in healthy volunteers to minimize respiratory movement with good tolerability and reproducibility. It is a feasible approach for lung motion control and could potentially be applied in accurate radiotherapy including carbon-ion radiotherapy through suppression of respiratory movement.

Rho GDP-dissociation inhibitor α is a potential prognostic biomarker and controls telomere regulation in colorectal cancer.

Rho GDP-dissociation inhibitor α (RhoGDIα) is an essential regulator for Rho GTPases. Although RhoGDIα may serve as an oncogene in colorectal cancer (CRC), the underlying mechanism is still unclear. We investigated the function, mechanism, and clinical significance of RhoGDIα in CRC progression. We founded that downregulation of RhoGDIα repressed CRC cell proliferation, motility, and invasion. Overexpression of RhoGDIα increased DNA damage response signals at telomeres, and led to telomere shortening in CRC cells, also being validated in 26 pairs of CRC tissues. Mechanistic studies revealed that RhoGDIα could promote telomeric repeat factor 1 (TRF1) expression through the phosphatidylinositol 3-kinase-protein kinase B signal pathway. Moreover, RhoGDIα protein levels were strongly correlated with TRF1 in CRC tissues. A cohort of 297 CRC samples validated the positive relationship between RhoGDIα and TRF1, and revealed that RhoGDIα and TRF1 levels were negatively associated with CRC patients' survival. Taken together, our results suggest that RhoGDIα regulate TRF1 and telomere length and may be novel prognostic biomarkers in colorectal cancer.