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Objective: The purpose of this study was to explore the predictive value of the neutrophil-to-lymphocyte ratio (NLR) on 30-day outcomes in patients with spontaneous intracerebral hemorrhage (ICH) after surgical treatment. Methods: This retrospective study utilized data from patients with ICH who underwent craniotomy or minimally invasive puncture and drainage (MIPD) between January 2015 and June 2021. The patients meeting the inclusion criteria were divided into two groups according to 30-day outcomes, namely, the favorable outcome group and the poor outcome group. Sex, age, time from onset to admission, vital signs at admission, admission Glasgow Coma Scale (GCS) score, diabetes mellitus, hypertension, hematoma volume, hematoma location, surgical approach, and NLR at different time points were all recorded and analyzed. Results: A total of 128 patients were finally enrolled in this study, including 32 and 96 patients in the favorable outcome group and the poor outcome group, respectively. During the course of ICH, the changing trend of NLR was to increase first and then decrease and peaked within 48 h after surgery. In the univariate analysis, systolic blood pressure, admission GCS score, hematoma volume, surgical approach, and NLR within 48 h after surgery were statistically significant. In the multivariable analysis, NLR within 48 h after surgery (odds ratio [OR] = 1.342, p < 0.001) was an independent risk factor of the 30-day outcomes in patients with ICH after surgical treatment. The receiver operating characteristic (ROC) analysis showed that the best predictive cut-off value for NLR within 48 h after surgery was 12.35 [sensitivity 82.9%, specificity 81.8%, and area under the curve (AUC) 0.877] and 14.46 (sensitivity 55.1%, specificity 87.5%, and area under the curve 0.731) for the MIPD group and the craniotomy group, respectively. Conclusions: In the process of ICH, the value of NLR was increased first and then decreased and peaked within 48 h after surgery. NLR within 48 h after surgery was an independent risk factor of the 30-day outcomes in patients with ICH. The peak NLR >12.35 or 14.46 in patients receiving MIPD or craniotomy reflected a poor prognosis, respectively.
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STUDY QUESTION: Does exogenous calcitonin improve the efficiency of implantation in mice by increasing uterine receptivity? SUMMARY ANSWER: The administration of calcitonin could improve the efficiency of implantation by increasing the expression of several receptivity-related genes in endometrial epithelial cells (EECs). WHAT IS KNOWN ALREADY: Calcitonin is one of the biomarkers of uterine receptivity, which is transiently produced in the uterine epithelia during the period of implantation both in humans and mouse. STUDY DESIGN, SIZE, DURATION: Hormone-replaced mice were used for in vivo experiments. To evaluate the effect of calcitonin on uterine receptivity, the expression of endometrial genes was analyzed 36 h after i.p. injection of 0.5 IU calcitonin in a treatment group versus saline in the control. To evaluate the effect of calcitonin on implantation efficiency in vivo, two groups received 0.5 IU or 2 IU calcitonin (i.p.) 24 h before embryo transfer, and a control group received saline (i.p.) (n = 18 mice per group). Implantation sites were counted 7 days after embryo transfer. The RL95-2 human endometrial carcinoma cell line was used to study the mechanisms underlying the effect of calcitonin on gene expression in the endometria. Using an in vitro model of endometrium-trophoblast interaction, established with RL95-2 cells and JAR (human choriocarcinoma cell line) trophoblast, endometrial receptivity was evaluated by comparing attachment and outgrowth of JAR spheroids in control and treatment groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: Uterine receptivity in ovariectomized mice was induced by injection of estradiol and progesterone. Expression of eight genes in murine endometrium and RL95-2 cells was analyzed by real-time RT-PCR, western blot, immunohistochemical analysis, flow cytometry and enzyme-linked immunosorbent assay. We tested the effects of a protein kinase C inhibitor, matrigel and an antibody against integrin αvß3 using RL95-2 cells and performed attachment and outgrowth assays using the in vitro model of endometrium-trophoblast interaction. Implantation efficiency was evaluated by counting the implantation sites after embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE: Calcitonin up-regulated αvß3 in RL95 cells, which in turn resulted in increased levels of the leukemia inhibitory factor (LIF) and heparin binding-epidermal growth factor (HB-EGF) mRNA (both P < 0.01 versus control) and protein (both P < 0.05 versus control). The attachment and expansion of JAR spheroids was promoted by pretreatment of EECs with calcitonin (P < 0.05 versus control) together with significantly increased expression of αvß3, LIF and HB-EGF. Moreover, the injection of calcitonin in the preimplantation phase increased the total number of implantation sites in treatment groups (55 in control versus 78 and 85 in 0.5 and 2 IU groups, respectively). Compared with the control group (3.11 ± 2.14), the average number of implantation sites in the 2 IU calcitonin treatment group increased (4.72 ± 1.87, P = 0.022). LIMITATIONS, REASONS FOR CAUTION: Experiments were performed in mice and human cell lines but not in primary cultures of human endometrial cells. WIDER IMPLICATIONS OF THE FINDINGS: The findings presented here have important implications, in that calcitonin administration (currently used for treatment of hypercalcemia or osteoporosis) may have clinical benefits in assisted reproduction programs, by facilitating endometrial receptivity and embryo implantation. However, further studies are required to confirm these findings. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by National Science Foundation of China (No. 81170619). There are no financial or commercial conflicts in this study.