ObjectiveTo investigate whether Bushen Huoxue prescription improves embryo implantation through regulating exosomal miRNA to enhance maternal-fetal interface communication based on Bushen Huoxue therapy. MethodsIn the animal experiment， all the rats （except for the blank group） were administered hydroxyurea （450 mg·kg^-1） via gavage for 10 d， as well as epinephrine （0.3 mg·kg^-1） and mifepristone （5.5 mg·kg^-1） via subcutaneous injection for 7 d to establish an implantation disorder model of kidney deficiency and blood stasis type. The Bushen Huoxue prescription （BSHX） groups were administered the prescription at different doses （7.30 g·kg^-1 for the high-dose group， 3.65 g·kg^-1 for the medium-dose group， and 1.83 g·kg^-1 for the low-dose group） via gavage. The dydrogesterone group was administered the corresponding medicine （2.63 mg·kg^-1） via gavage. After intervention for 10 days， uterine histopathological changes were observed via hematoxylin-eosin （HE） staining. Mucin （MUC1）， forkhead box protein O1 （FoxO1）， and homeobox A10 （HoxA10） expression levels were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Cell experiment selected primary endometrial epithelial cells （EEC） and trophoblast cells （TC） as research subjects. Exosome-free medicated serum was prepared by ultracentrifugation and cultured in complete medium. Exosomes were isolated from cell supernatants by ultracentrifugation for cross-co-culture. After 48 h， migration and invasion abilities were assessed by scratch and Transwell assays. Sequencing was then performed on EEC-origin exosomal miRNA. ResultsThe model rats exhibited thin endometrium， along with reduced blood vessels， glandules， and pinopode numbers. BSHX improved endometrial morphology and increased pinopode numbers. MUC1， FoxO1， and HoxA10 expressions were downregulated in the model rats， while these parameters were upregulated after BSHX medium- and high-dose intervention. In the cell experiment， after exosome-free medicated serum intervention for 24 h， migration and invasion abilities were enhanced in the BSHX groups （P<0.01）. In EEC-origin exosomal miRNA sequencing， gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses revealed enrichment in biological processes （gastrulation， neuronal differentiation， alongside cell development and regeneration）， involving the mitogen-activated protein kinase （MAPK）， FoxO1， Wnt， mammalian target of rapamycin （mTOR）， and tumor necrosis factor （TNF） signaling pathways. ConclusionBSHX promotes embryo implantation by improving endometrial receptivity via regulating exosomal miRNA. These findings provide potential targets for exosomal miRNA-based assisted reproductive strategies and a novel theoretical basis for infertility treatment by traditional Chinese medicine.

OBJECTIVE: To investigate the clinical outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) after surgeries in Yunnan Province. METHODS: We retrospectively analyzed the demographic features, vascular risk factors, severity at admission, and aneurysm locations in 85 patients with aSAH receiving surgical interventions in Yunnan Province. All the patients were treated by aneurysm clipping or coiling and followed up for clinical outcomes and recovery of daily activities evaluated by modified Rankin Scale (mRS) and Activities of Daily Living (ADL) scale, respectively. RESULTS: Thirty-four of the patients (40.0%) underwent aneurysm clipping and 51 (60.0%) underwent aneurysm coiling. During a median follow- up period of 66.23 months (IOR, 12.03 months), 84.7% of the patients had low mRS scores, and 78.8% lived independently. The WFNS grade at admission was significantly correlated with the follow-up mRS scores (95%: 1.48-19.09, =0.011) and ADL (95%: 2.55-28.77, < 0.001). Multivariate analysis showed that age (95%: 1.02-1.23, =0.017; 95%: 1.00-1.15, =0.038) and a high WFNS grade at admission (95%: 2.19-141.48, =0.007; 95%: 2.84-82.61, =0.002) were independent predictors of both mRS and ADL scores at follow-up. There was no significant difference in clinical outcomes or the length of hospital stay between the two treatment strategies ( > 0.05), but the cost of hospitalization was significantly higher in coiling group than in the clipping group ( < 0.001). CONCLUSIONS Both aging and a high WFNS grade at admission are associated with a poor prognosis of aSAH, for which aneurysm clipping and coiling have similar long- term outcomes, but for patients with a high WFNS score, aneurysm clipping is favored over coiling in terms of health economics.

Objective To study the effects of osteopontin (OPN) on the nuclear mechanics of bone marrow-derived mesenchymal stem cells (BMSCs) as well as its involved mechanisms. Methods The BMSC migration was evaluated using the Transwell assay. An atomic force microscope (AFM) was used to determine the elastic modulus of the BMSC nucleus and analyze the changes in the nuclear mechanics of the BMSCs after treatment with OPN. The activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase1/2 (ERK1/2) was measured by Western blot. The role of the FAK-ERK1/2 signaling pathway in mediating the OPN-affected BMSC nuclear mechanics was investigated by employing a specific inhibitor. RT-PCR and Western blot were used to detect the expression of Lamin A/C at mRNA and protein levels in the BMSCs, respectively. Results The elastic modulus of the BMSC nucleus exhibited a significant decrease after OPN treatment compared with that of the control group. OPN could upregulate the phosphorylation level of FAK and ERK1/2, but the inhibitor of FAK or ERK1/2 restored the OPN-decreased elastic modulus of the BMSC nucleus and inhibited the BMSC migration significantly. After treatment with OPN, the expression of Lamin A/C in the BMSCs reduced significantly, and such a reduced expression could be suppressed by the inhibitor of FAK or ERK1/2. Conclusions OPN could probably downregulate the expression of Lamin A/C of the BMSCs via the FAK-ERK1/2 signaling pathway, decrease the stiffness of the BMSC nucleus, and promote the migration of the BMSCs. The research outcomes provide the experimental evidence for further understanding the mechanism of the OPN-regulated BMSC migration and its potential clinical application.