Association between the mean perfusion pressure and the risk of acute kidney injury in critically ill patients with sepsis: a retrospective cohort study.

BACKGROUND: Mean perfusion pressure (MPP) has recently emerged as a potential biomarker for personalized management of tissue perfusion in critically ill patients. However, its association with the occurrence of acute kidney injury (AKI) in septic patients and the optimal MPP range remain uncertain. Therefore, this study aims to investigate the relationship between MPP and AKI in critically ill patients with sepsis. METHODS: We identified 5867 patients with sepsis from the MIMIC-IV database who met the inclusion and exclusion criteria. The exposure variable was the first set of MPP measured within 24 h after ICU admission with invasive hemodynamic monitoring. The primary outcome was the incidence of AKI at 7 days following ICU admission according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Secondary outcomes included in-hospital mortality, lengths of ICU, and hospital stay. Optimal cut-off point for MPP were determined using the Youden index, and multivariable logistic regression was employed to examine the association between MPP and AKI. Subgroup analyses were conducted to enhance result robustness. Kaplan-Meier survival analysis was utilized to evaluate in-hospital mortality rates categorized by MPP. RESULTS: A total of 5,867 patients with sepsis were included in this study, and the overall incidence of AKI was 82.3%(4828/5867). Patients were categorized into low MPP (< 63 mmHg) and high MPP (≥ 63 mmHg) groups using the optimal ROC curve-derived cut-off point. The incidence of AKI in the low MPP group was higher than that in the high MPP group (87.6% vs. 78.3%, P < 0.001). Multivariable logistic regression analysis adjusted for confounding factors revealed that each 1 mmHg increase in MPP as a continuous variable was associated with a 2% decrease in AKI incidence within 7 days of ICU admission (OR:0.98, 95%CI:0.97-0.99, P < 0.001). When MPP was used as a categorical variable, patients in the high MPP group had a lower risk of AKI than those in the low MPP group (OR:0.71, 95%CI:0.61-0.83, P = 0.001). Subgroup analyses demonstrated a consistent association between MPP and AKI risk across all variables assessed (P for interaction all > 0.05). Kaplan-Meier curve analysis demonstrated a higher survival rate during hospitalization in the high MPP group compared to the low MPP group (Log-rank test, P < 0.0001). CONCLUSIONS: Lower levels of MPP are associated with an increased incidence of AKI at 7 days in critically ill patients with sepsis.

Preparation of decellularized bone graft material with supercritical carbon dioxide extraction technique. / è¶ ä¸´ç•ŒäºŒæ°§åŒ–ç¢³èƒå–ç”¨äºŽå¼‚ç§è„±ç»†èƒžéª¨ä¿®å¤ææ–™çš„åˆ¶å¤‡.

OBJECTIVES: To evaluate the immunogenicity and osteogenic ability of animal-derived bone graft material decellularized with supercritical carbon dioxide. METHODS: Porcine femurs were randomly divided into two groups after preliminary treatment, and decellularized with conventional method (conventional control group) or supercritical carbon dioxide (experimental group). Clearance rate of galactose-α-1, 3-galactose (α-Gal) and residual DNA of the two groups were analyzed to assess the immunogenicity of the xenogenic materials. Clearance rate of α-Gal was determined by enzyme-linked immunosorbent assay and residual DNA was detected by fluorescence method. Nine SPF-grade male athymic nude mice of 6 weeks old were randomly divided into experimental group, conventional control group and positive control group. Samples were implanted over biceps femoris muscle of athymic nude mice, the explants were collected 4 weeks post implantation, hematoxylin and eosin (HE) staining and immunohistochemistry were applied to determine the osteogenic ability and bone tissue-associated protein expressions of the implants. RESULTS: The clearance rates of α-Gal antigen in the experimental group and the conventional control group were (99.09±0.26)% and (30.18±2.02)%, respectively (t=58.67, P<0.01). The residual DNA of the experimental group, the conventional control group and the positive control group were (13.49±0.07) ng/mg, (15.20±0.21) ng/mg and (14.70±0.17) ng/mg, the residual DNA in the experimental group was significantly lower than that in the conventional control group (t=－13.41, P<0.01) and the positive control group (t=－11.30, P<0.01). HE staining showed that multiple bone formation centers with active osteogenesis and rich bone marrow were observed in experimental group 4 weeks after implantation, only a small number of bone formation centers were observed in the conventional control group and the positive control group, with no obvious osteoblasts present. Immunohistochemistry results indicated that the expressions of alkaline phosphatase, Runt-related transcription factor 2, typeⅠcollagen and osteocalcin in the experimental group showed an increasing trend compared with those in the conventional control group and the positive control group. CONCLUSIONS: Compared with clinically used demineralized bone matrix and bone graft material decellularized with conventional method, bone graft material decellularized with supercritical carbon dioxide exhibits lower immunogenicity and better osteogenic ability.

Preparation and Mechanism Analysis of Stainless Steel AOD Slag Mixture Base Materials.

To promote resourceful utilization of argon oxygen decarburization (AOD) slag, this research developed a new three-ash stabilized recycled aggregate with AOD slag, cement, fly ash (FA), and recycled aggregate (RA) as raw materials. The AOD slag was adopted as an equal mass replacement for fly ash. The application of this aggregate in a road base layer was investigated in terms of its mechanical properties and mechanistic analysis. First, based on a cement: FA ratio of 1:4, 20 sets of mixed proportion schemes were designed for four kinds of cement dosage and AOD slag replacement rates (R/%). Through compaction tests and the 7-day unconfined compressive strength test, it was found that a 3% cement dosage met the engineering requirements. Then, the unconfined compressive strength test, indirect tensile strength test, compressive rebound modulus test, and expansion rate test were carried out at different age thresholds. The results showed that the mixture's strength, modulus, and expansion rate increased initially and then stabilized with age, while the strength and modulus initially increased and then decreased with increasing R. Secondly, based on X-ray diffraction (XRD) and scanning electron microscopy (SEM) used to analyze the mechanism, it was found that the strength, modulus, and expansion rate of the new material can be promoted by blending AOD slag, due to its ability to fully stimulate the hydration reaction and pozzolanic reaction of the binder. Finally, based on the strength and modulus results, R = 3% was identified as the optimal ratio, which provides a reference point for the effective application of AOD slag and RA in road base materials.

Wenhua Juanbi Recipe Attenuates Rheumatoid Arthritis via Inhibiting miRNA-146a-Mediated Autophagy.

Background: Wenhua Juanbi Recipe (WJR) is widely used for the treatment of rheumatoid arthritis (RA) in China. However, its mechanism of action remains unclear. This study was designed to investigate the potential therapeutic effects of WJR on the proliferation and apoptosis of synovial fibroblasts in RA and its efficacy in inhibiting miRNA-146a-mediated cellular autophagy. Methods: A collagen-induced arthritis (CIA) Wistar rat model was established. The model rats were administered WJR or methotrexate (MTX) to assess the therapeutic effect of the drugs. The chemical components of WJR were analyzed using UPLC-Q/TOF-MS. Histological changes; miRNA-146a, ATG5, ATG7, ATG12, Beclin1, LC3II, Bax, and Bcl2 expression; synovial apoptosis; and cellular proliferation were assessed. Primary synovial fibroblasts (FLS) were cultured in vitro using tissue block and transfected with miRNA-146a; an autophagy inducer was added to FLS, inhibiting the PI3K/AKT/mTOR pathway. FLS were cocultured with WJR-containing serum to observe the effects of miRNA-146a-mediated autophagy via the PI3K/AKT/mTOR pathway on CIA-affected rats. Results: Forty and thirty-one compounds were identified in WJR in the positive and negative ion modes, respectively. WJR significantly reduced toe swelling, arthritis scores, and expression of miRNA-146a and autophagy genes (ATG5, ATG7, ATG12, Beclin1, LC32, and Bcl2). Moreover, Bax expression, apoptosis, and attenuated proliferation were observed in rats. WJR could, therefore, regulate autophagy by influencing the miRNA-146a-mediated PI3K/AKT/mTOR pathway, which induces apoptosis and proliferation of FLS. Conclusion: WJR can inhibit autophagy, apoptosis, and proliferation in a CIA rat model by inhibiting the miRNA-146a-mediated PI3K/AKT/mTOR pathway.