Comparative analysis of clonal evolution among patients with right- and left-sided colon and rectal cancer.

Tumor multiregion sequencing reveals intratumor heterogeneity (ITH) and clonal evolution playing a key role in tumor progression and metastases. Large-scale high-depth multiregional sequencing of colorectal cancer, comparative analysis among patients with right-sided colon cancer (RCC), left-sided colon cancer (LCC), and rectal cancer (RC), as well as the study of lymph node metastasis (LN) with extranodal tumor deposits (ENTDs) from evolutionary perspective remain weakly explored. Here, we recruited 68 patients with RCC (18), LCC (20), and RC (30). We performed high-depth whole-exome sequencing of 206 tumor regions including 176 primary tumors, 19 LN, and 11 ENTD samples. Our results showed ITH with a Darwinian pattern of evolution and the evolution pattern of LCC and RC was more complex and divergent than RCC. Genetic and evolutionary evidences found that both LN and ENTD originated from different clones. Moreover, ENTD was a distinct entity from LN and evolved later.

Dose-response of vasopressin in a rat model of asphyxial cardiac arrest.

The advantage of vasopressin over epinephrine in the treatment of cardiac arrest (CA) is still being debated, and it is not clear whether a high dose of vasopressin is beneficial or detrimental during or after cardiopulmonary resuscitation (CPR) in a rat model of CA. In this study, asphyxial CA was induced in 40 male Sprague-Dawley rats. After 10 minutes of asphyxia, CPR was initiated; and the effects of different doses of vasopressin (low dose, 0.4 U/kg; medium dose, 0.8 U/kg; and high dose, 2.4 U/kg; intravenous; n = 10 in each group) and a saline control (isotonic sodium chloride solution, 1 mL, intravenous) were compared. Outcome measures included the rate of restoration of spontaneous circulation (ROSC) and changes of hemodynamic and respiratory variables after ROSC. The rates of ROSC were 1 of 10 in the saline group and 8 of 10 in each of the 3 vasopressin groups. There were no differences in mean aortic pressure or changes of respiratory function after CPR among the vasopressin groups. However, the heart rate was lower in the high-dose vasopressin group than in the low- and medium-dose groups. These findings indicate that different doses of vasopressin result in a similar outcome of CPR, with no additional benefits afforded by a high dose of vasopressin during or after CPR, in a rat model of asphyxial CA. The mechanism and physiologic significance of the relative bradycardia that occurred in the high-dose vasopressin group are currently unknown and require further investigation.