[Preliminary application of postoperative fast track transfer to intensive care unit for the geriatric hip fractures under enhanced recovery after surgery].

Objective: To develop a fast track transfer to intensive care unit (ICU) for the perioperative high-risk elderly patients after hip fracture surgery and analyze the preliminary clinical effect of the application. Methods: From January 2014 to December 2017, before the application of postoperative fast track transfer to ICU, the clinical data of 195 elderly patients with hip fracture were included in a retrospective analysis. Among 195 hip fracture patients, 18 were transferred to ICU post operation (non-fast track group). Multivariate logistic regression analysis was applied to investigate relevant risk factors for transferring to ICU after hip fracture surgery. Based on risk factors acquired from the analysis and clinical experience, the fast track transfer to ICU for the perioperative high-risk elderly patients after hip fracture surgery was constructed according to the preliminary and experiential criteria. From January 2018 to December 2019, the clinical data of 70 patients (fast track group) who were transferred to ICU after hip fracture surgery through the fast track were collected and compared with non-fast track group. Results: Multivariate regression analysis revealed that American Society of Anesthesiologists classification(≥Ⅲ) (OR=4.260, 95%CI:1.157-15.683, P=0.029), pre-hospital stage (≥48 h) (OR=4.301, 95%CI:1.212-15.266, P=0.024), hemoglobin concentration at admission(<90 g/L) (OR=7.979, 95%CI:1.936-32.889, P=0.004), coronary heart disease as one comorbidity(OR=6.063, 95%CI:1.695-21.693, P=0.006) were independent risk factors for transferring to ICU after hip fracture surgery. There were no significant difference in gender, age, fracture type, hemoglobin concentration at admission and time of pre-hospital stage between the non-fast track group and fast track group(all P>0.05). However, the number of comorbidities in the fast track group was significantly higher than that in the non-fast track group (Z=-1.995, P=0.046). The time to surgery, postoperative hospital stay, and length of hospital stay in fast track group were all significantly less than those in non-fast track group (Z=-2.121, -2.726, -3.130, all P<0.05). Also, there were fewer medical consultations needed and fewer patients who stayed in ICU more than or equal to 2 nights in fast track group than that in non-fast track group(all P<0.05). There were no significant difference in the rate of patients who transferred from the general ward to ICU after transferring from ICU to the general ward, the proportion of patients who received more than or equal to 4 departments, operation time, hospitalization expense, mortality during hospitalization, 30-day mortality and 90-day mortality after operation between the two groups(all P>0.05). Conclusions: The fast track constructed in this study can reduce time to surgery, postoperative hospitalization stay and length of hospitalization stay for the perioperative high-risk elderly patients with hip fractures and is a specific clinical application of eras concept based on multidisciplinary team.

MiR-25 overexpression promotes fracture healing by activating the Wnt signaling pathway.

OBJECTIVE: To study the mechanism of micro-ribonucleic acid (miR)-25 in regulating the fracture healing in rats. MATERIALS AND METHODS: A total of 45 male Sprague-Dawley (SD) rats were selected and randomly divided into group A [Phosphate Buffered Saline (PBS), n=15], group B (mimics NC, n=15) and group C (miR-25 mimics, n=15). The fracture model in rats was established via operation in all groups. From 1 d after the successful modeling, 50 µL (2 nmoL) of PBS was intraperitoneally injected into rats in group A, an equal amount of mimics NC was injected into rats in group B, and an equal amount of miR-25 mimics was injected into rats in group C. The above agents were injected once a week for consecutive 6 weeks. Fracture healing in rats was evaluated via X-ray imaging. At the same time, miR-25 expression in the three groups was detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Protein expressions of ß-catenin, proliferating cell nuclear antigen (PCNA) and bone morphogenetic protein-2 (BMP-2) in the three groups were detected via Western blotting. The OCN-, PCNA- and BMP-2-positive osteoblasts in the three groups were detected via immunohistochemical staining and were further quantified. Moreover, the biomechanical properties of femoral fracture healing in the three groups were analyzed via the 4-point bending flexural test. RESULTS: The X-ray examination of the femoral fracture healing at postoperative 1 and 7 weeks revealed that the fracture line disappeared, and both callus formation and fracture healing were good in miR-25 mimics group. In PBS group and mimics NC group, a few fracture lines could be observed, and both callus formation and fracture healing were poor. RT-PCR data showed that the expression level of miR-25 significantly increased in the miR-25 mimics group compared with that in the other two groups, and the differences were statistically significant (p<0.01). Western blotting analyses showed upregulated levels of ß-catenin, PCNA and BMP-2 in the miR-25 mimics group compared with those in the control group, and the differences were statistically significant (p<0.01). Immunohistochemical staining manifested that the numbers of OCN-, PCNA- and BMP-2-positive osteoblasts in miR-25 mimics group markedly increased compared with that in the other two groups (p<0.01), suggesting that osteoblast differentiation in miR-25 mimics group was affected. The above immunohistochemical results indicated that the osteoblast differentiation at the fracture end in miR-25 mimics group was markedly enhanced compared with that in control groups. The results of the biomechanical test of femur specimens at 7 weeks after operation showed that in miR-25 mimics group, the maximum load, fracture energy and stiffness increased by 188%, 333% and 90%, respectively, compared with those in the PBS group (p<0.01). It is indicated that miR-25 promoted the mechanical properties of fracture healing. CONCLUSIONS: The overexpression of miR-25 in the fracture in rats promotes fracture healing by activating the Wnt signaling pathway.

Structure-activity relationships of analogs of the endogenous brain peptides Tyr-MIF-1 and Tyr-W-MIF-1.

Analogs of the naturally occurring peptides Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) and Tyr-W-MIF-1 (Tyr-Pro-Trp-GLy-NH2) were synthesized and investigated for their opiate agonist as well as antagonist activity in the guinea pig ileum assay. [Tyr5]-Tyr-MIF-1 and the endogenous Tyr-W-MIF-1 were the most potent opiate agonists among the 20 compounds tested. Several analogs showed antiopiate activity in the ileum from morphine-tolerant animals as measured by attenuation of the agonistic effect of DAMGO, which inhibits electrically stimulated contractions of the ileum. The binding activity of the analogs at mu opiate receptors was determined by displacement of [3H]-DAMGO in rat brain. Tyr-W-MIF-1 and its analogs were more potent than Tyr-MIF-1 and its analogs in this binding assay. Thus, Tyr-MIF-1, Tyr-W-MIF-1 and several of their analogs could act as opiate agonists as well as antagonists.

Isolation of a heptapeptide Val-Val-Tyr-Pro-Trp-Thr-Gln (valorphin) with some opiate activity.

Bovine hypothalamic tissue was extracted and purified by solid phase extraction and several reversed-phase HPLC steps. The amino acid sequence of the purified peptide was determined by Edman degradation to be Val-Val-Tyr-Pro-Trp-Thr-Gln. This was confirmed by comparison of its chromatographic behavior with that of the synthetic peptide, and mass spectrometric analysis resulted in a mass identical to the calculated mass for this peptide. This heptapeptide shows homology with residues 32-38 of the beta-chain of bovine hemoglobin. The peptide inhibited the electrically induced contractions of the guinea pig ileum muscle preparation; this inhibition was reversible by naloxone. It also inhibited the binding of 125I-DAMGO (selective for mu receptors) to rat brain with an IC50 of 10 microM and the binding of 3H-DPDPE (selective for sigma receptors) with an IC50 of 185 microM. With two valines at the N-terminus and some opiate activity, valorphin seems a suitable name for this newly isolated peptide.