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Background Chronic subdural hematomas (CSDHs) are one of the most common neurosurgical conditions. The standard surgical technique includes burr-hole craniostomy, followed by intraoperative irrigation and placement of subdural closed-system drainage. The drainage is generally removed after 48 hours, which can be described as fixed-time drainage strategy. According to literature, the recurrence rate is 5–33% with this strategy. In our retrospective study, postoperative hematoma volume was found to significantly increase the risk of recurrence. Based on these results, an exhaustive drainage strategy is conducted to minimize postoperative hematoma volume and achieve a low recurrence rate and good outcomes. Methods This is a prospective, multicenter, randomized controlled trial designed to include 304 participants over the age of 18–90 years presenting with a symptomatic CSDH verified on cranial computed tomography or magnetic resonance imaging. Participants will be randomly allocated to perform exhaustive drainage (treatment group) or fixed-time drainage (control group) after one-burr hole craniostomy. The primary endpoint will be recurrence indicating a reoperation within 6 months. Discussion This study will validate the effect and safety of exhaustive drainage after one-burr hole craniostomy in reducing recurrence rates and provide critical information to improve CSDH surgical management. Trial registration Clinicaltrials.gov, NCT04573387. Registered on October 5, 2020. (https://www.clinicaltrials.gov/ct2/show/study/NCT04573387.)

Bone cancer pain (BCP) is a difficult-to-treat pathologic condition that impairs the patient's quality of life. The effective therapy options for BCP are restricted due to the unknown pathophysiology. Transcriptome data were obtained from the Gene Expression Omnibus (GEO) database and differentially expressed gene (DEGs) extraction was performed. Differentially expressed genes analysis (DEGs) integrated with pathological targets found 68 genes in the study. Butein was discovered as a possible medication for BCP after the 68 genes were submitted to the Connectivity Map (CMap) 2.0 database for drug prediction. To collect the butein targets, we used the CTD, SEA, TargetNet, and Super-PRED databases. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed butein's pharmacological effects, indicating that butein may aid in treating BCP by altering the hypoxia-inducible factor, NF-kappa B, angiogenesis, and sphingolipid signaling pathways. Moreover, the pathological targets integrated with drug targets were obtained as the shared gene set A (GSA), which was analyzed by ClueGO and MCODE. Biological process analysis and MCODE algorithm further analyzed that BCP related targets were mainly involved in signal transduction process and ion channel-related pathways. Next, we integrated targets related to network topology parameters and targets of core pathways, identified PTGS2, EGFR, JUN, ESR1, TRPV1, AKT1 and VEGFA as butein regulated hub genes by molecular docking, which play a critical role in its analgesic effect. This study lays the scientific groundwork for elucidating the mechanism underlying butein's success in the treatment of BCP.

Liver fibrosis is a chronic liver disease that can lead to cirrhosis, liver failure, and hepatocellular carcinoma, and it is associated with long-term adverse outcomes and mortality. As a primary resource for complementary and alternative medicine, traditional Chinese medicine (TCM) has accumulated a large number of effective formulas for the treatment of liver fibrosis in clinical practice. However, studies on how to systematically optimize TCM formulas are still lacking.To provide a methodological reference for the systematic optimization of TCM formulae against liver fibrosis and explored the underlying molecular mechanisms; To provide an efficient method for searching for lead compounds from natural sources and developing from herbal medicines; To enable clinicians and patients to make more reasonable choices and promote the effective treatment toward those patients with liver fibrosis.TCM formulas related to treating liver fibrosis were collected from the Web of Science, PubMed, the China National Knowledge Infrastructure (CNKI), Wan Fang, and the Chinese Scientific Journals Database (VIP). Furthermore, the TCM compatibility patterns were mined using association analysis. The core TCM combinations were found by designing an optimized formulas algorithm. Finally, the hub target proteins, potential molecular mechanisms, and active compounds were explored through integrative pharmacology and docking-based inverse virtual screening (IVS) approaches.We found that the herbs for reinforcing deficiency, activating blood, removing blood stasis, and clearing heat were the basis of TCM formulae patterns. Furthermore, the combination of Salviae Miltiorrhizae (Salvia miltiorrhiza Bunge; Chinese salvia/Danshen), Astragali Radix (Astragalus membranaceus (Fisch.) Bunge; Astragalus/Huangqi), and Radix Bupleuri (Bupleurum chinense DC.; Bupleurum/Chaihu) was identified as core groups. A total of six targets (TNF, STAT3, EGFR, IL2, ICAM1, PTGS2) play a pivotal role in TCM-mediated liver fibrosis inhibition. (-)-Cryptotanshinone, Tanshinaldehyde, Ononin, Thymol, Daidzein, and Formononetin were identified as active compounds in TCM. And mechanistically, TCM could affect the development of liver fibrosis by regulating inflammation, immunity, angiogenesis, antioxidants, and involvement in TNF, MicroRNAs, Jak-STAT, NF-kappa B, and C-type lectin receptors (CLRs) signaling pathways. Molecular docking results showed that key components had good potential to bind to the target genes.In summary, this study provides a methodological reference for the systematic optimization of TCM formulae and exploration of underlying molecular mechanisms.

Corydalis yanhusuo W. T. Wang, a traditional Chinese herbal medicine, has been used as an analgesic for thousands of years and it also promotes blood circulation. In this study, 33 Corydalis yanhusuo alkaloid active components were acquired from Traditional Chinese Medicine Database and Analysis Platform (TCMSP). A total of 543 pain-related targets, 1774 arrhythmia targets, and 642 potential targets of these active components were obtained using Swiss Target Prediction, GeneCards, Open Target Platform, and Therapeutic Target Database. Fifty intersecting targets were visualized through a Venn diagram, KEGG and GO pathway enrichment analysis. The analysis proposed that sodium ion channels are likely potential targets of Corydalis yanhusuo active components as analgesia and anti-arrhythmia agents. Molecular docking showed that the 33 components could bind to Nav1.7 and Nav1.5 (two subtypes of ion channel proteins) with different binding energies. In a patch clamp study, dihydrosanguinarine and dihydrochelerythrine, two monomers with the strongest binding effects, could inhibit the peak currents and promote both activation and inactivation phases of Nav1.5. Meanwhile, dihydrosanguinarine and dihydrochelerythrine could also inhibit peak currents and promote the activation phase of Nav1.7. Therefore, the findings from this study provide valuable information for future uses of traditional Chinese medicines to treat pain and cardiovascular disease.

Background: CFTR, a chloride channel protein expressed on cell membrane, plays an important role in the transdermal transport of salt and the regulation of intracellular ion concentration, and may be closely related to the occurrence and development of cancer. Methods: In this study, the expression level of CFTR in hepatocellular carcinoma (HCC) and its correlation with metastasis and prognosis were predicted by TGCA, GEPIA and GTEx databases. By constructing MHCC97H with stable overexpression of CFTR and HepG2 with stable interference expression of CFTR cell lines, the expression level of CFTR and its correlation with proliferation and metastasis of HCC cells were preliminarily verified by Western Blot, MTT, Transwell and PI staining. In order to further clarify the potential related mechanism, it was predicted through String and Genecards databases, and the expression level of related proteins was verified by Western Blot. And it was further verified by orthotopic HCC transplanted tumor models combined with in vivo imaging system, western blot and immunohistochemical. Finally, CLUE Command database and autodock was used to predict the potential anti-HCC drugs targeting CFTR.Results: The results showed that the expression of CFTR was significantly lower in human HCC tissues (predicted by clinical data) and HCC cells (HepG2, MHCC97L, MHCC97H), and the expression level was negatively correlated with clinical stage, prognosis (predicted by clinical data) and metastatic potency of HCC cells. CFTR could regulate the metastasis and proliferation of HCC by regulating the expression of MMP2, MMP9, E-cadherin, N-cadherin, and CyclinB1 proteins in vitro and in vivo. CFTR could regulate the expression of HSP90, TERT, and DNAJC6, which meant that HSP90, TERT, and DNAJC6 might build a bridge for CFTR to regulate proliferation and metastasis proteins. Parecoxib might be one potential anti-HCC drug by targeting CFTR.Conclusions: The above studies further clarify a potential new mechanism of HCC occurrence and metastasis, and provide potential new targets and treatment schemes for the diagnosis and treatment of HCC.