Molecular mechanisms underlying the therapeutic effects of Linggui Zhugan decoction in stroke: Insights from network pharmacology and single-cell transcriptomics analysis.

Linggui Zhugan decoction (LZD), a traditional Chinese medicine formula, has demonstrated significant therapeutic effects in managing poststroke cognitive impairment and hemiplegia. However, the precise molecular mechanisms underlying its efficacy remain incompletely elucidated. The active ingredients and target proteins of LZD were retrieved from the traditional Chinese medicine systems pharmacology database and analysis platform database, which is specifically designed for traditional Chinese medicine research. The stroke-related genes were obtained from publicly available databases. Protein-protein interaction, enrichment analysis, and single-cell data analysis were conducted to identify key cells, targets, and pathways. Molecular docking was employed to assess the binding affinity between key components and targets. Network pharmacology analysis identified 190 active ingredients and 248 targets in LZD. These targets were significantly enriched in processes and pathways such as cellular response to lipid, orexin receptor pathway, and were significantly associated with Cerebral infarction and Middle Cerebral Artery Occlusion. Intersection analysis with 2035 stroke-related genes revealed 144 potential targets, which exhibited 2870 interactions and were significantly enriched in signaling pathways such as PI3K-AKT single pathway, MAPK single pathway, and tumor necrosis factor single pathway. Gene set variation analysis showed that the targets of LZD exhibited higher enrichment scores in microglia, M2 macrophages, endothelial cells, and neutrophils, while lower enrichment scores were observed in oligodendrocytes. Furthermore, molecular docking demonstrated a strong binding affinity between key active ingredients and targets. Network pharmacology and single-cell sequencing analysis elucidated the key cells, pathways, targets, and components involved in the therapeutic mechanism of LZD for the treatment of stroke.

Malignant melanoma resection and reconstruction with the first manifestation of lumbar metastasis: A case report.

BACKGROUND: Malignant melanoma (MM) has shown an increasing incidence worldwide, and a potential to metastasize to almost any part of the body. Clinically, MM with bone metastasis as the initial manifestation is extremely rare. Spinal metastatic MM can cause spinal cord or nerve root compression, resulting in severe pain and paralysis. Currently, the primary clinical treatments for MM are surgical resection in conjunction with chemotherapy, radiotherapy, and immunotherapy. CASE SUMMARY: Here, we report the case of a 52-year-old male who presented to the clinic with progressive low back pain and limited nerve function. No primary lesion or spinal cord compression was detected from computed tomography and magnetic resonance imaging of the lumbar vertebrae and positron emission tomography scan. A lumbar puncture biopsy confirmed the diagnosis of lumbar spine metastatic MM. Following surgical resection, the patient's quality of life improved, symptoms were relieved, and comprehensive treatment was initiated, which prevented recurrence. CONCLUSION: Spinal metastatic MM is clinically rare, and may cause neurological symptoms, including paraplegia. Currently, the clinical treatment plan consists of surgical resection in combination with chemotherapy, radiotherapy, and immunotherapy.

Fatigue Crack Growth Behavior and Fracture Toughness of EH36 TMCP Steel.

The fatigue crack growth behavior and fracture toughness of EH36 thermo-mechanical control process (TMCP) steel were investigated by fatigue crack growth rate testing and fracture toughness testing at room temperature. Scanning electron microscopy was used to observe the fracture characteristics of fatigue crack propagation and fracture toughness. The results indicated that the microstructure of EH36 steel is composed of ferrite and pearlite with a small amount of texture. The Paris formula was obtained based on the experimental data, and the value of fracture toughness for EH36 steel was also calculated using the J-integral method. The observations conducted on fatigue fracture surfaces showed that there were a lot of striations, secondary cracks and tearing ridges in the fatigue crack propagation region. Additionally, there existed many dimples on the fracture surfaces of the fracture toughness specimens, which indicated that the crack was propagated through the mechanism of micro-void growth/coalescence. Based on the micromechanical model, the relationship between the micro-fracture surface morphology and the fracture toughness of EH36 steel was established.

Novel compound heterozygous mutations in the MYO15A gene in autosomal recessive hearing loss identified by whole-exome sequencing.

BACKGROUND: Inherited genetic defects play an important role in congenital hearing loss, contributing to about 60% of deafness occurring in infants. Hereditary nonsyndromic hearing loss is highly heterogeneous, and most patients with a presumed genetic etiology lack a specific molecular diagnosis. METHODS: By whole exome sequencing, we identified responsible gene of family 4794 with autosomal recessively nonsyndromic hearing loss (ARNSHL). We also used DNA from 56 Chinese familial patients with ARNSHL (autosomal recessive nonsyndromic hearing loss) and 108 ethnicity-matched negative samples to perform extended variants analysis. RESULTS: We identified MYO15A c.IVS25+3G>A and c.8375 T>C (p.V2792A) as the disease-causing mutations. Both mutations co-segregated with hearing loss in family 4794, but were absent in the 56 index patients and 108 ethnicity-matched controls. CONCLUSIONS: Our results demonstrated that the hearing loss of family 4794 was caused by novel compound heterozygous mutations in MYO15A.