Isoimperatorin attenuates bone loss by inhibiting the binding of RANKL to RANK.

Osteoporosis, an immune disease characterized by bone mass loss and microstructure destruction, is often seen in postmenopausal women. Isoimperatorin (ISO), a bioactive, natural furanocoumarin isolated from many traditional Chinese herbal medicines, has therapeutic effects against various diseases; however, its effect on bone homeostasis remains unclear. In this study, we investigated the effect of ISO on the differentiation and activation of osteoclast and its molecular mechanism in vitro, and evaluated the effect of ISO on bone metabolism by ovariectomized (OVX) rat model. In vitro experiments showed that ISO affected RANKL-induced MAPK, NFAT, NFATc1 trafficking and expression, osteoclast F-actin banding, osteoclast-characteristic gene expression, ROS inhibitory activity, and calcium oscillations, NF-κB signaling pathway. In vivo experiments showed that oral administration of ISO effectively reduced bone loss caused by ovariectomy and retained bone mass.Collectively, ISO inhibits RANK/RANKL binding, thereby reducing the activity of NFATc1, calcium, and ROS and inhibiting osteoclast generation. In addition, ISO protects bone mass by slowing osteoclast production and downregulating NFATc1 gene and protein expression in the bone tissue microenvironment and inhibits OVX-induced bone loss in vivo.

Dehydromiltirone inhibits osteoclast differentiation in RAW264.7 and bone marrow macrophages by modulating MAPK and NF-κB activity.

Background: Osteoporosis is a type of systematic metabolic bone disease caused by the decrease in osteogenic activity or excessive resorption of bone with the relative enhancement of osteoclast function. As osteoporosis seriously affects the quality of patients' life, effective drugs are needed to treat this disease. Based on the combination of network pharmacology and cellular studies, this study aimed to investigate the probable mechanism of Dehydromiltirone (DHT) in the treatment of osteoporosis. Method: The targets of DHT in osteoporosis were searched using the PharmGKB, OMIM, and Genecard platforms. The PPI core targets, and the GO and KEGG enrichment analysis results were obtained using Cytoscape software, and the David and Metascape databases, respectively. The network pharmacology results were also verified via in vitro cellular experiments. Results: Through network pharmacology and docking analysis, we found DHT was involved in peptide tyrosine phosphorylation, cell surface receptor tyrosine kinase signaling pathways, and MAPK signaling pathways. According to the molecular docking results, the binding of DHT to MAPK14 was more stable than other proteins, which suggests that DHT may affect osteoclast formation through the MAPK signaling pathway. Moreover, DHT was found to inhibit the expression of osteoclast-associated genes, including NFATc1, CTSK, c-Fos, Acp5, and MMP9; as well as the phosphorylation of P38, ERK, and JNK of the MAPK signaling pathway; and the degradation of IκB-α of NF-κB signaling pathway. Conclusion: DHT exhibited an anti-osteoclastogenesis effect by reducing the expression of related genes, ultimately inhibiting bone resorption in vitro.

A Secure Storage and Sharing Scheme of Stroke Electronic Medical Records Based on Consortium Blockchain.

The maintenance and sharing of electronic medical records are one of the essential tasks in the medical treatment combination. Traditional cloud-based electronic medical record storage system is difficult to realize data security sharing. The tamper resistance and traceability of blockchain technology provide the possibility for the sharing of highly sensitive medical data. This paper proposes a safe sharing scheme of stroke electronic medical records based on the consortium blockchain. The scheme adopts the storage method of ciphertext of medical records stored in the cloud and index of medical records stored on the blockchain. The privacy protection mechanism proposed in this paper innovatively combines proxy reencryption and searchable encryption which supports patient pseudoidentity search. The mechanism could achieve controllable sharing of medical records and precise search. According to the organizational characteristics of the stroke medical treatment combination, this paper proposes an improved Practical Byzantine Fault Tolerance mechanism to reach a consensus between consensus nodes. Then, the proposed scheme is analyzed and evaluated from three aspects of medical record integrity, user privacy, and data security. The results show that the scheme can not only ensure the privacy of patient identity information and private key data but also resist the tampering and deletion attacks of internal and external malicious nodes on the medical record data. Therefore, the proposed scheme is conducive to the improvement of the timeliness of stroke treatment and the safe sharing of electronic medical records in stroke medical treatment combination.

Risk Factors for Pulmonary Cement Embolism (PCE) After Polymethylmethacrylate Augmentation: Analysis of 32 PCE Cases.

OBJECTIVE: Pulmonary cement embolism (PCE) is an underestimated but potentially fatal complication after cement augmentation. Although the treatment and follow-up of PCE have been reported in the literature, the risk factors for PCE are so far less investigated. This study aims to identify the preoperative and intraoperative risk factors for the development of PCE. METHODS: A total of 1,373 patients treated with the polymethylmethacrylate (PMMA) augmentation technique were retrospectively included. Patients with PCE were divided into vertebral augmentation group and screw augmentation group. Possible risk factors were collected as follows: age, sex, bone mineral density, body mass index, diagnosis, comorbidity, surgical procedure, type of screw, augmented level, number of augmented vertebrae, fracture severity, presence of intravertebral cleft, cement volume, marked leakage in the paravertebral venous plexus, and periods of surgery. Binary logistic regression analyses were used to analyze independent risk factors for PCE. RESULTS: PCE was identified in 32 patients, with an incidence rate of 2.33% (32 of 1,373). For patients who had undergone vertebral augmentation, marked leakage in the paravertebral venous plexus (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.1-10.3; p=0.000) and previous surgery (OR, 16.1; 95% CI, 4.2-61.0; p=0.007) were independent risk factors for PCE. Regarding patients who had undergone screw augmentation, the marked leakage in the paravertebral venous plexus (OR, 4.2; 95% CI, 0.5-37.3; p=0.004) was the main risk factor. CONCLUSION: Marked leakage in the paravertebral venous plexus and previous surgery were significant risk factors related to PCE. Paravertebral leakage and operator experience should be concerned when performing PMMA augmentation.