Association between average mean arterial pressure and 30-day mortality in critically ill patients with sepsis and primary hypertension: a retrospective analysis.

Sepsis and hypertension pose significant health risks, yet the optimal mean arterial pressure (MAP) target for resuscitation remains uncertain. This study investigates the association between average MAP (a-MAP) within the initial 24 h of intensive care unit admission and clinical outcomes in patients with sepsis and primary hypertension using the Medical Information Mart for Intensive Care (MIMIC) IV database. Multivariable Cox regression assessed the association between a-MAP and 30-day mortality. Kaplan-Meier and log-rank analyses constructed survival curves, while restricted cubic splines (RCS) illustrated the nonlinear relationship between a-MAP and 30-day mortality. Subgroup analyses ensured robustness. The study involved 8,810 patients. Adjusted hazard ratios for 30-day mortality in the T1 group (< 73 mmHg) and T3 group (≥ 80 mmHg) compared to the T2 group (73-80 mmHg) were 1.25 (95% CI 1.09-1.43, P = 0.001) and 1.44 (95% CI 1.25-1.66, P < 0.001), respectively. RCS revealed a U-shaped relationship (non-linearity: P < 0.001). Kaplan-Meier curves demonstrated significant differences (P < 0.0001). Subgroup analysis showed no significant interactions. Maintaining an a-MAP of 73 to 80 mmHg may be associated with a reduction in 30-day mortality. Further validation through prospective randomized controlled trials is warranted.

Synergistic cardioprotective effects of rAAV9-CyclinA2 combined with fibrin glue in rats after myocardial infarction.

The present study aimed to investigate the protective effects of rAAV9-CyclinA2 combined with fibrin glue (FG) in vivo in rats after myocardial infarction (MI). Ninety male Sprague-Dawley rats were randomized into 6 groups (15 in each group): sham, MI, rAAV9-green fluorescent protein (GFP) + MI, rAAV9-CyclinA2 + MI, FG + MI, and rAAV9-CyclinA2 + FG + MI. Packed virus (5 × 1011vg/ml) in 150 µl of normal saline or FG was injected into the infarcted myocardium at five locations in rAAV9-GFP + MI, rAAV9-CyclinA2 + MI, and rAAV9-CyclinA2 + FG + MI groups. The sham, MI, and FG + MI groups were injected with an equal volume of normal saline or FG at the same sites. Five weeks after injection, echocardiography was performed to evaluate the left ventricular function. The expressions of CyclinA2, proliferating cell nuclear antigen (PCNA), and phospho-histone-H3 (H3P), vascular density, and infarct area were assessed by Western blot, immunohistochemistry, immunofluorescence, and Masson staining. As a result, the combination of rAAV9-CyclinA2 and FG increased ejection fraction and fractional shortening compared with FG or rAAV9-CyclinA2 alone. The expression level of CyclinA2 was significantly higher in the rAAV9-CyclinA2 + FG + MI group compared with the rAAV9-CyclinA2 + MI and FG + MI groups (70.1 ± 1.86% vs. 14.74 ± 2.02%, P < 0.01; or vs. 50.13 ± 3.80%; P < 0.01). A higher expression level of PCNA and H3P was found in the rAAV9-CyclinA2 + FG + MI group compared with other groups. Comparing with other experiment groups, collagen deposition and the infarct size significantly decreased in rAAV9-CyclinA2 + Fibrin + MI group. The vascular density was much higher in the rAAV9-CyclinA2 + FG + MI group compared with the rAAV9-CyclinA2 + MI group. We concluded that fibrin glue combined with rAAV9-CyclinA2 was found to be effective in cardiac remodeling and improving myocardial protection.

Therapeutic delivery of cyclin-A2 via recombinant adeno-associated virus serotype 9 restarts the myocardial cell cycle: an in vitro study.

Cyclin­A2, which is downregulated following birth, has previously been established as a key regulator of the cell cycle. The present study aimed to detect the effects of cyclin­A2 on myocardial cells by using recombinant adeno­associated virus 9 (rAAV9). Sixty mice were selected and randomly divided into two groups (n=30). The control group were injected with saline and the experimental group were transfected with the rAAV9­cyclinA2­CMV vector by intravenous injection into the tail vein. Tissues were harvested at two and four weeks following injection. Cyclin­A2 expression levels and localization were evaluated using western blot and immunohistochemical analyses. DNA synthesis and mitosis in the myocardium were confirmed by analyzing proliferating cell nuclear antigen (PCNA) and phospho­histone H3 (H3P) expression levels. Expression of Cyclin­A2 in the myocardium commenced two weeks following tail vein injection in the cyclin­A2­treated group, while no expression was observed in the control group. Four weeks following injection, expression levels of cyclin­A2 were higher than those observed at two weeks following injection into the myocardium (two weeks: 0.146±0.013 vs. 27.1±3.33%, P<0.001; four weeks: 0.142±0.107 vs. 74.4±3.36%, P<0.001). PCNA displayed increased expression levels in the cyclin­A2­treated group (two weeks: 13.1±0.54 vs. 65.8±3.44%, P<0.001; four weeks: 13.2±0.55 vs. 71.2±1.58%, P<0.001); however, no change was observed in those of the control group. By contrast, no significant difference was observed in mitosis marker H3P expression levels between the two groups. Immunohistochemical analysis of cyclin­A2 indicated cytoplasmic, but not nuclear, localization. cyclin­A2 and PCNA expression levels in the liver, lung and kidney showed no significant difference between the two groups (P>0.05). It was therefore concluded that the delivery of cyclin­A2 via rAAV9 to the mouse myocardium restarted the myocardial cell cycle, thereby establishing steady and specific expression in the myocardium. Furthermore, the effect of Cyclin­A2 on the myocardium may provide a novel method for achieving cardiac regeneration following cardiac injury.