Myelin formation is considered the last true "invention" in the evolution of vertebrate nervous system cell structure. The rapid jumping pulse propagation achieved by myelin enables the high conduction speed that is the basis of human movement, sensation, and cognitive function. As a key structure in the brain, white matter is the gathering place of myelin. However, with age, white matter-associated functions become abnormal and a large number of myelin sheaths undergo degenerative changes, causing serious neurological and cognitive disorders. Despite the extensive time and effort invested in exploring myelination and its functions, numerous unresolved issues and challenges persist. In-depth exploration of the functional role of myelin may bring new inspiration for the treatment of central nervous system (CNS) diseases and even mental illnesses. In this study, we conducted a comprehensive examination of the structure and key molecules of the myelin in the CNS, delving into its formation process. Specifically, we propose a new hypothesis regarding the source of power for myelin expansion in which membrane compaction may serve as a driving force for myelin extension. The implications of this hypothesis could provide valuable insights into the pathophysiology of diseases involving myelin malfunction and open new avenues for therapeutic intervention in myelin-related disorders.
Myelin Sheath/metabolism* ; Humans ; Central Nervous System/metabolism* ; Animals

Objective To investigate the relationship between the serum FMS-like tyrosine kinase 3 ligand(Flt3L),progranulin(PGRN)levels and the disease risk and disease outcome of patients with acute lympho-blastic leukemia(ALL).Methods A total of 104 patients with ALL admitted to the hospital from September 2019 to September 2021 were selected as the research subjects.ALL patients were divided into the low-risk group(n=34),the medium-risk group(n=39),and the high-risk group(n=31)according to the disease risk.The levels of serum Flt3L and PGRN of the patients at admission were detected by enzyme-linked immu-nosorbent assay.Pearson correlation analysis was used to analyze the relationship between serum Flt3L,PGRN in ALL patients and the risk of ALL disease.According to the follow-up results of ALL patients,they were divided into the good prognosis group(n=81)and the poor prognosis group(n=23).The receiver oper-ating characteristic curve and the area under the curve(AUC)were used to analyze the evaluation value of se-rum Flt3L and PGRN for the prognosis of ALL patients,and multivariate Cox regression was used to analyze the prognostic risk factors of ALL patients.Results The serum Flt3L levels in the low-risk group and the medium-risk group were higher than those in the high-risk group,and the difference was statistically signifi-cant(P＜0.05).The serum PGRN levels in the low-risk group and the medium-risk group were lower than those in the high-risk group,and the difference was statistically significant(P＜0.05).Serum Flt3L in ALL patients was negatively correlated with the risk of ALL disease(r=-0.461,0.593,P＜0.05).Serum PGRN in ALL patients was positively correlated with the risk of ALL disease(r=0.593,P＜0.05).The proportions of white blood cell count ≥50 × 109/L,hemoglobin＜90 g/L,and serum PGRN level in the poor prognosis group were higher than those in the good prognosis group,while the serum Flt3L level was lower than that in the good prognosis group,and the differences were statistically significant(P＜0.05).The AUC of serum Flt3L and PGRN in evaluating the prognosis of ALL patients were 0.762(95％CI:0.717-0.816),0.815(95％CI:0.764-0.863),and 0.915(95％CI:0.866-0.964),respectively.White blood cell count ≥50 × 109/L,hemoglobin＜90 g/L,Flt3L＜92.07 pg/mL,and PGRN≥335.14 pg/mL were risk factors affecting the prognosis of ALL patients(P＜0.05).Conclusion The levels of serum Flt3L and PGRN in ALL patients are related to the disease risk and disease outcome of ALL.The combined detection of the two has a good eval-uation value for the prognosis of adult ALL patients.

ObjectiveTo explore the potential mechanisms of a baicalin-geniposide combination against cerebral ischemia using a network pharmacology strategy.MethodWe used network pharmacology integrating drug-target-disease interactions to identify key pathways which were validated in a rat middle cerebral artery occlusion model treated with baicalin (55 mg/kg), geniposide (5 mg/kg), or their 11:1 combination. Therapeutic efficacy and mechanistic insights were evaluated using triphenyltetrazolium chloride staining, Evans blue assay, enzyme-linked immunosorbent assay, and Western blot.ResultsThe results revealed that the nuclear factor-kappa B (NF-κB) signaling pathway is inhibited in combination treatment of cerebral ischemia. Ten targets were identified as key nodes in the protein–protein interaction network: interleukin 6 (IL-6), interleukin-1β, interleukin 18, C–C motif ligand 2, C–C motif ligand 4, interleukin 10, interferon-γ-inducible protein 10, C–C motif ligand 3, tumor necrosis factor-α (TNF-α), interleukin-1α. The baicalin-geniposide combination significantly reduced infarct volume, improved neurological deficits, and alleviated brain edema/blood–brain barrier leakage compared with monotherapy. Additionally, it significantly inhibited toll-like receptor 4 (TLR4)/NF-κB signaling and downregulated pro-inflammatory cytokines TNF-α and IL-6 levels.ConclusionThe baicalin-geniposide combination alleviated cerebral ischemia-reperfusion injury by synergistically suppressing the TLR4/NF-κB pathway and its downstream inflammatory factors.

Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.

OBJECTIVE To evaluate the efficacy and safety of Huoxue Xiaoyi Granule in inhibiting the recurrence of endometrio-sis(EMs)after conservative operation,and to provide evidence for Chinese medicine in inhibiting the recurrence of EMs.METHODS A total of 72 patients with qi-stagnation and blood-stasis after EMs operation were selected as the study objects and randomly divid-ed into the Chinese medicine group and the Western medicine group,36 cases in each group.The Chinese medicine group was treated with Huoxue Xiaoyi Granule,and the Western medicine group was treated with GnRH-α.The postoperative recurrence rate,TCM syn-drome score,carbohydrate antigen 125(CA125),dysmenorrhea score,pelvic pain score,pregnancy rate,serum sex hormones[estra-diol(E2),luteinizing hormone(LH),follicle stimulating hormone(FSH)]and safety indexes of the two groups were observed.RE-SULTS At 9 months and 12 months after surgery,the total TCM syndrome scores of the two groups of patients were significantly re-duced(P<0.05),and the Chinese medicine group was better than the Western medicine group(P<0.05);12 months later,the TCM total clinical curative rate in the Chinese medicine group was better than that in the Western medicine group;after surgery,the serum CA125 levels,dysmenorrhea scores and pelvic pain severity of the two groups of patients were significantly reduced(P<0.05,P<0.01);during treatment,the total incidence of adverse reactions in the Chinese medicine group was lower than that in the Western medicine group(P<0.01);the recurrence rate of the Chinese medicine group was slightly lower than that of the Western medicine group,but there was no statistical difference(P>0.05).CONCLUSION Huoxue Xiaoyi Granule can significantly improve TCM syndromes in patients with qi-stagnation and blood-stasis after EMs surgery.It is safe and has equivalent efficacy to GnRH-α in pre-venting postoperative recurrence of EMs,and worthy of clinical promotion and application.

Objective To observe the value of CT radiomics nomogram for predicting Ki-67 expression of thymus epithelial tumors.Methods Totally 163 patients with thymus epithelial tumor,including 114 patients in training set and 49 patients in validation set were retrospectively enrolled.The patients were further divided into low expression(＜50％)and high expression(≥50％)subgroups according to Ki-67 index.Multivariate logistic regression analysis was performed to screen independent predicting factors of Ki-67 expression in thymus epithelial tumors,and clinical-CT model was constructed.The optimal radiomics features were extracted and screened based on chest plain and venous phase enhanced CT images,respectively.Then radiomics modelplain and radiomics modelenhanced were constructed,and Radscoreplain and Radscoreenhanced were calculated,respectively.The nomogram model was constructed based on clinical-CT model,Radscoreplain and Radscoreenhanced.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each model for predicting Ki-67 expression of thymus epithelial tumors.Results Patient's gender and enhanced CT value of lesion were both independent predicting factors of Ki-67 expression in thymus epithelial tumors(both P＜0.05).The AUC of clinical-CT model,radiomics modelplain,radiomics modelenhanced and nomogram model for predicting Ki-67 expression was 0.736,0.814,0.836 and 0.857 in training set,which was 0.746,0.746,0.750 and 0.799 in validation set,respectively.Conclusion CT radiomics nomogram could be used to predict Ki-6 7 expression of thymus epithelial tumors.

Objective To explore the mechanism of Tetrastigma hemsleyanum(TH)in the treatment of hepatocellular carcinoma(HCC)through network pharmacology;To conduct experimental verification.Methods The active components and targets of TH were screened from CNKI,Wanfang Data,VIP,PubMed,Web of Science and TCMSP databases.OncoDB.HCC,GeneCards,OMIM and DrugBank databases were searched to collect HCC-related targets,and Cytoscape software was used to construct drug-active components-target-disease network.Protein-protein interaction(PPI)was analyzed using STRING database.The GO and KEGG pathway enrichment were analyzed using the Metascape database.AutoDock were used for molecular docking of key targets and their corresponding components.MTT colorimetric assay and cell morphology observation were used to detect the proliferation of human liver cancer HepG2 cells.Cell migration and invasion were observed through cell scratch experiment and Transwell chamber experiment.Annexin Ⅴ/PI double staining and flow cytometry were used to detect cell apoptosis,while RT-PCR and Western blot were used to detect related protein expression.Results The network pharmacological analysis showed that there were 16 active components in TH,228 action targets,and 157 targets related to HCC.JUN,AKT1,MAPK1 and TP53 would be the core targets of TH for the treatment of HCC.The core pathways were IL-17 signaling pathway,TNF signaling pathway,P53 signaling pathway,and PI3K-Akt signaling pathway,which were closely related to HCC.The molecular docking results showed that there was a good binding effect between the main active components and the core target of TH.The cell experiment results showed that each dose group of TH could significantly inhibit the proliferation,migration,and invasion of HepG2 cells,promote apoptosis,down-regulate the expressions of AP-1 and MAPK1,and up-regulate the expression of TP53.Conclusion TH can inhibit the proliferation,migration and invasion of HepG2 cells and promote their apoptosis.The mechanism may be related to the down-regulation of AP-1,MAPK1 protein expression and up-regulation of TP53 protein expression.

Objective:To analyze the clinical application of different diagnostic methods for heart failure with preserved ejection fraction (HFpEF) in maintenance hemodialysis (MHD) patients.Methods:It was a single-center retrospective cohort study. Uremia patients who underwent hemodialysis at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2020 to June 2021 were enrolled. The demographic characteristics, laboratory indicators, and echocardiography parameters were collected. The 2016 European Society of Cardiology (ESC) criteria, H 2FPEF score [composite score based on weighted scores of heavy (H), hypertensive (H), atrial fibrillation (F), pulmonary hypertension (P), elder (E), and filling pressure (F)], and Heart Failure Association (HFA) -PEFF score [including pre-test assessment (P), echocardiography and natriuretic peptide score (E), functional testing (F) and final aetiology (F)] were used to diagnose HFpEF, respectively, and the difference of three diagnostic methods was compared. The association between HFpEF diagnosed by the three methods and poor outcomes (all-cause death, cardiovascular death) was analyzed. Results:A total of 160 MHD patients were included, whose age was (58.5±13.4) years, median dialysis age was 5.0 (2.3, 9.6) years, median H 2FPEF score was 2 (1, 3), median HFA-PEFF score was 4 (3, 5), and 92 (57.5%) were males. Of these patients, 118 patients (73.8%) met the 2016 ESC criteria for diagnosis of HFpEF, 4 (2.5%) met H 2FPEF score for diagnosis of HFpEF, and 56 (35.0%) met HFA-PEFF score for diagnosis of HFpEF. The consistency of three methods in diagnosing HFpEF was poor with κ values of 0.018 between ESC criteria and H 2FPEF score, 0.322 between ESC criteria and HFA-PEFF score, and 0.056 between H 2FPEF score and HFA-PEFF score. After a median follow-up of 2.6 years, 20 (12.5%) of the 160 MHD patients died. The Kaplan-Meier survival analysis showed a significant difference in mortality between patients diagnosed with HFpEF and those without using the H 2FPEF score (Log-rank test, χ2=6.95, P=0.008). After adjusting for demographic and clinical parameters, multivariate Cox regression analysis showed that HFpEF diagnosed by HFA-PEFF score was associated with all-cause mortality ( HR=2.73, 95% CI 1.07-6.98, P=0.036) and cardiovascular mortality ( HR=4.77, 95% CI 1.31-17.30, P=0.018). Conclusions:The 2016 ESC criteria, H 2FPEF score, and HFA-PEFF score have high heterogeneity and poor consistency in diagnosing HFpEF in MHD patients. Among the three diagnostic methods, only the diagnosis based on HFA-PEFF score is associated with the prognosis of MHD patients. The HFA-PEFF score can be used to assess the risk of HFpEF in MHD patients, and more clinical studies are needed to further verify it in the future.

Uveal melanoma (UM) poses a significant lethality, with approximately 50% of those developing metastases surviving less than one year. In the progression of UM, vasculogenic mimicry (VM) induced by hypoxia plays a pivotal role, which also partially explains the resistance of UM to anti-angiogenic therapies. Nevertheless, the crucial molecular mechanisms underlying VM in the progression of UM remain unclear. We identified ubiquitin conjugating enzyme E2 G2 (UBE2G2) as a critical suppressor through transcriptomic sequencing and metastasis correlation screening. In UM, hypoxia-induced VM and metastasis are markedly exacerbated by UBE2G2 knockdown and significantly alleviated by its overexpression. Mechanistically, UBE2G2 directly binds to galectin 3 binding protein (LGALS3BP) and forms a complex with the E3 ubiquitin ligase tripartite motif containing 38 (TRIM38), facilitating ubiquitination-mediated degradation of LGALS3BP at the K104 residue. Furthermore, UBE2G2 inhibits oncogenic phenotypes by inactivating intracellular PI3K/AKT signaling and reprogramming the tumor microenvironment. Therefore, targeting intercellular and intracellular molecular mechanisms of the hypoxia-UBE2G2-LGALS3BP axis may contribute to developing various therapeutic strategies for UM.

[Objective]To investigate the therapeutic effect and molecular mechanism of Chinese medicine Saffron on Parkinson's disease(PD)based on network pharmacology and molecular docking.[Methods]The pharmacodynamic components of Saffron included in the analysis were determined through the pharmacological database and literature research of the Chinese medicine system.With the help of compound target database and disease target database,the corresponding targets of saffron components and PD targets were predicted,respectively.Enrichment analysis of compound-disease intersection targets was made by using R procedures and referencing correlated R-packages.Construction of protein-protein interaction(PPI)networks and analysis of node-related topological parameters.Simulate molecular docking to verify binding properties of representative compounds and key targets.The pharmacodynamic properties of Saffron acid on key targets were preliminarily evaluated by experiments.[Results]The 8 components of saffron with druggable potential corresponded to 279 targets,PD had 2 183 disease targets,and a total of 98 intersection targets of compounds and diseases were obtained.Enrichment analysis showed that the compound-disease intersection target was involved in biological processes such as reactive oxygen radical synthesis and metabolism,neuroinflammation and mitogen-activated protein kinase(MAPK)signaling pathway.The key targets identified by PPI network analysis were tumor necrosis factor(TNF)and signal transducer and activator of transcription 3(STAT3).Molecular docking showed that saffron glycosides and saffron acids had stronger binding activity with TNF.Experiments had shown that saffron acid can reduce the transcription levels of lipopolysaccharide-induced cytoinflammatory factor TNF,interleukin-1β(IL-1β)and inducible nitric oxide oxide synthase(iNOS).[Conclusion]Saffron can be used as a candidate for PD treatment,and its neuroprotective effect may involve the interaction and synergy of many targets and signaling pathways,which deserves special attention to the activity of saffron acid against central nervous system inflammation.