Ranibizumab biosimilar(Shanghai United Cell Biotechnology Co. Ltd.)

The discovery of multi-functional small-molecule compounds with potent blood-brain barrier (BBB) protective effect for treating ischemic stroke (IS) is a relatively unexplored area. Herein, a series of 33 novel hybrid molecules were rationally designed and synthesized via incorporating 4-methoxybenzyl alcohol-mimicking pharmacophore (With potential BBB protective activity) into 3-n-butylphthalide (NBP) scaffold. Among them, the representative compound 30 exhibited enhanced neuroprotective, anti-inflammatory, anti-oxidative, and BBB protective activities than those of NBP. After the chiral resolution, the neuroprotective potency of R-enantiomer (R-30) was identified to be more potent than the S-enantiomer. In vivo, R-30 significantly reduced infarct volume and markedly preserved BBB integrity. Furthermore, it displayed a good safety profile in acute toxicity study. These findings support the potential of R-30 as a multi-functional anti-IS candidate that deserves further development.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive technique used to control non-compressible torso hemorrhage. However, the optimal degree of partial occlusion that offers maximum therapeutic benefit remains unclear. This study aimed to identify the optimal partial inflation volume for REBOA.

In a swine model of hemorrhagic shock, nine healthy female pigs were randomly assigned to three groups based on balloon inflation volume: 30% (R30), 60% (R60), and 100% (R100) of the volume required to eliminate the contralateral femoral arterial waveform. Hemodynamic variables, fluid and vasopressor requirements, and biochemical markers were evaluated during balloon occlusion and resuscitation following 40% blood volume-controlled hemorrhage.

The R30 group showed higher mean arterial pressure during resuscitation and required less fluid and norepinephrine than those of the R100 group. The mean heart rate significantly differed over time among the groups, with more gradual changes in the R30 group. Markers of ischemia-reperfusion injury (lactate, pH, blood urea nitrogen, and creatinine) similarly exhibited significant temporal differences. Post hoc analysis revealed significant pH differences between the groups. The plasma lactate and creatinine levels were significantly lower in the R30 group than those in the other two groups.

In this swine hemorrhagic shock model, partial REBOA with 30% balloon inflation maintained hemodynamic stability while reducing metabolic derangement compared with higher ballon volumes of 60% and 100% inflation. A strategy involving partial inflation targeting approximately 30%, followed by monitoring the blood pressure trend while using a vasoconstrictor, if necessary, may have potential clinical utility.