BACKGROUND:Human periodontal ligament stem cells are potential functional cells for periodontal tissue engineering.However,long-term in vitro culture may lead to reduced stemness and replicative senescence of periodontal ligament stem cells,which may impair the therapeutic effect of human periodontal ligament stem cells. OBJECTIVE:To investigate the effect of oxymatrine on the stemness maintenance and osteogenic differentiation of periodontal ligament stem cells in vitro,and to explore the potential mechanism. METHODS:Periodontal ligament stem cells were isolated from human periodontal ligament tissues by tissue explant enzyme digestion and cultured.The surface markers of mesenchymal cells were identified by flow cytometry.Periodontal ligament stem cells were incubated with 0,2.5,5,and 10 μg/mL oxymatrine.The effect of oxymatrine on the proliferation activity of periodontal ligament stem cells was detected by CCK8 assay.The appropriate drug concentration for subsequent experiments was screened.Western blot assay was used to detect the expression of stem cell non-specific proteins SOX2 and OCT4 in periodontal ligament stem cells.qRT-PCR and western blot assay were used to detect the expression levels of related osteogenic genes and proteins in periodontal ligament stem cells. RESULTS AND CONCLUSION:(1)The results of CCK8 assay showed that 2.5 μg/mL oxymatrine significantly enhanced the proliferative activity of periodontal stem cells,and the subsequent experiment selected 2.5 μg/mL oxymatrine to intervene.(2)Compared with the blank control group,the protein expression level of SOX2,a stem marker of periodontal ligament stem cells in the oxymatrine group did not change significantly(P>0.05),and the expression of OCT4 was significantly up-regulated(P<0.05).(3)Compared with the osteogenic induction group,the osteogenic genes ALP,RUNX2 mRNA expression and their osteogenic associated protein ALP protein expression of periodontal ligament stem cells were significantly down-regulated in the oxymatrine+osteogenic induction group(P<0.05).(4)The oxymatrine up-regulated the expression of stemness markers of periodontal ligament stem cells and inhibited the bone differentiation of periodontal ligament stem cells,and the results of high-throughput sequencing showed that it may be associated with WNT2,WNT16,COMP,and BMP6.

Diabetic retinopathy(DR)has emerged as the leading cause of vision loss among working-age people in many countries under the increasing prevalence of diabetes and the longevity of the population. The pathogenesis of DR is complicated and has not been fully elucidated at present, while the treatment methods of DR have not been greatly improved, mainly retinal laser photocoagulation, anti-vascular endothelial growth factor(VEGF)treatment and vitrectomy surgery. The current treatment methods not only have shortcomings, but also bring serious economic burden to patients. Therefore, new methods are needed to explore the pathogenesis of DR, discover new treatments or improve current treatments, and improve the satisfaction of DR patients. In recent years, the identification and quantification of proteins expressed in blood, retina, vitreous humor, aqueous humor, and tears of all observable DR patients and DR rats and differentially expressed proteins after drug intervention have provided new ideas for further exploring the pathogenesis, diagnosis and treatment of DR with the rise of proteomics, which put forward new insights into early detection and treatment.The proteomics of DR in recent years are reviewed, in order to provide new ideas for the diagnosis and treatment of DR.

Diabetic retinopathy(DR)has emerged as the leading cause of vision loss among working-age people in many countries under the increasing prevalence of diabetes and the longevity of the population. The pathogenesis of DR is complicated and has not been fully elucidated at present, while the treatment methods of DR have not been greatly improved, mainly retinal laser photocoagulation, anti-vascular endothelial growth factor(VEGF)treatment and vitrectomy surgery. The current treatment methods not only have shortcomings, but also bring serious economic burden to patients. Therefore, new methods are needed to explore the pathogenesis of DR, discover new treatments or improve current treatments, and improve the satisfaction of DR patients. In recent years, the identification and quantification of proteins expressed in blood, retina, vitreous humor, aqueous humor, and tears of all observable DR patients and DR rats and differentially expressed proteins after drug intervention have provided new ideas for further exploring the pathogenesis, diagnosis and treatment of DR with the rise of proteomics, which put forward new insights into early detection and treatment.The proteomics of DR in recent years are reviewed, in order to provide new ideas for the diagnosis and treatment of DR.

Objective To describe the significance of the pretreatment inflammatory indicators in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after undergoing radical radiotherapy. Methods The data of 246 ESCC patients who underwent radical radiotherapy were retrospectively collected. Receiver operating characteristic (ROC) curves were drawn to determine the optimal cutoff values for platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). The Kaplan-Meier method was used for survival analysis. We conducted univariate and multivariate analyses by using the Cox proportional risk regression model. Software R (version 4.2.0) was used to create the nomogram of prognostic factors. Results The results of the ROC curve analysis showed that the optimal cutoff values of PLR, NLR, and SII were 146.06, 2.67, and 493.97, respectively. The overall response rates were 77.6% and 64.5% in the low and high NLR groups, respectively (P<0.05). The results of the Kaplan-Meier survival analysis revealed that the prognosis of patients in the low PLR, NLR, and SII group was better than that of patients in the high PLR, NLR, and SII group (all P<0.05). The results of the multivariate Cox regression analysis showed that gender, treatment modalities, T stage, and NLR were independent factors affecting the overall survival (OS). In addition, T stage and NLR were independent factors affecting the progression-free survival (PFS) (all P<0.05). The nomogram models of OS and PFS prediction were established based on multivariate analysis. The C-index values were 0.703 and 0.668. The calibration curves showed excellent consistency between the predicted and observed OS and PFS. Conclusion The pretreatment values of PLR, NLR, and SII are correlated with the prognosis of patients with ESCC who underwent radical radiotherapy. Moreover, NLR is an independent factor affecting the OS and PFS of ESCC patients. The NLR-based nomogram model has a good predictive ability.

ObjectiveThe controllability changes of structural brain network were explored based on the control and brain network theory in young smokers, this may reveal that the controllability indicators can serve as a powerful factor to predict the sleep status in young smokers. MethodsFifty young smokers and 51 healthy controls from Inner Mongolia University of Science and Technology were enrolled. Diffusion tensor imaging (DTI) was used to construct structural brain network based on fractional anisotropy (FA) weight matrix. According to the control and brain network theory, the average controllability and the modal controllability were calculated. Two-sample t-test was used to compare the differences between the groups and Pearson correlation analysis to examine the correlation between significant average controllability and modal controllability with Fagerström Test of Nicotine Dependence (FTND) in young smokers. The nodes with the controllability score in the top 10% were selected as the super-controllers. Finally, we used BP neural network to predict the Pittsburgh Sleep Quality Index (PSQI) in young smokers. ResultsThe average controllability of dorsolateral superior frontal gyrus, supplementary motor area, lenticular nucleus putamen, and lenticular nucleus pallidum, and the modal controllability of orbital inferior frontal gyrus, supplementary motor area, gyrus rectus, and posterior cingulate gyrus in the young smokers’ group, were all significantly different from those of the healthy controls group (P<0.05). The average controllability of the right supplementary motor area (SMA.R) in the young smokers group was positively correlated with FTND (r=0.393 0, P=0.004 8), while modal controllability was negatively correlated with FTND (r=-0.330 1, P=0.019 2). ConclusionThe controllability of structural brain network in young smokers is abnormal. which may serve as an indicator to predict sleep condition. It may provide the imaging evidence for evaluating the cognitive function impairment in young smokers.

Through network pharmacology and molecular docking technology, combined with in vitro experiment verification, we explored the mechanism of action of Porana racemosa Roxb. (PRA) in the treatment of rheumatoid arthritis (RA), and provided a modern pharmacological basis for the treatment of RA by PRA. The potential target of chemical components in the analyzed moth rattan was predicted by Swiss Target Prediction database; OMIM, GeneCards, TTD and Disgenet databases were used to search the disease targets of RA; the protein interaction (PPI) network and medicine-composition-target network were constructed using STRING database and Cytoscape software; GO (gene ontology) functional enrichment and KEGG (kyoto encyclopedia of genes and genomes) pathway analysis were carried out using DAVID database, and molecular docking software was used to dock the potentially active ingredients of PRA and core targets; finally, MH7A cells were selected for cell viability, scratch healing and mRNA expression level analysis of key genes to explore the effects of PRA and their potentially active ingredients on the proliferation, migration and apoptosis of MH7A cells. In this study, a total of 628 potentially active ingredient targets, 1 890 RA targets and 235 intersection targets were identified. It was screened that the potentially active ingredients of RA treatment by PRA were ethylcaffeate, N-p-coumaroyltyramine, 9,12,15-octadecatrienoic acid, methyl ester and so on, and the core targets involved tumor necrosis factor (TNF), matrix metalloproteinase 9 (MMP9), prostaglandin-endoperoxide synthase 2 (PTGS2) and so on. 1 200 GO entries and 166 KEGG pathway entries were obtained from the enrichment analysis; molecular docking results showed that N-p-coumaroyltyramine and ethylcaffeate had good binding activity with TNF, MMP9, cysteine-aspartate protease 3 (CASP3), PTGS2, B-cell lymphoma 2 (BCL2) proteins. In vitro experiments showed that PRA, ethylcaffeate and N-p-coumaroyltyramine could inhibit the proliferation, migration and invasion of MH7A cells, up-regulate the expression of apoptosis-related gene CASP3 mRNA, and down-regulate the expression of MMP9, PTGS2 and BCL2 mRNA, and it can also down-regulate the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) mRNA and PI3K and p-AKT proteins. This study preliminarily revealed that the treatment of RA by PRA may be related to proliferation, migration, invasion, apoptosis and regulation of PI3K/AKT signaling pathway.

Background::Very low birth weight (VLBW) infants are the key populations in neonatology, wherein morbidity and mortality remain major challenges. The study aimed to analyze the clinical characteristics of VLBW infants.Methods::A retrospective cohort study was conducted in West China Second Hospital between January 2016 and December 2021. Neonates with a birth weight of <1500 g were included. Mortality, care practices, and major morbidities were analyzed, and compared with those of previous 7 years (2009-2015).Results::Of the total 1750 VLBW, 1386 were infants born with birth weight between 1000-1499 g and 364 infants were born with weight below 1000 g; 42.9% (751/1750) required delivery room resuscitation; 53.9% (943/1750) received non-invasive ventilation only; 38.2% (669/1750) received invasive ventilation; 1517 VLBW infants received complete treatment. Among them, 60.1% (912/1517) of neonates had neonatal respiratory distress syndrome (NRDS), 28.7% (436/1517) had bronchopulmonary dysplasia (BPD), 22.0% (334/1517) had apnea, 11.1% (169/1517) had culture-confirmed sepsis, 8.4% (128/1517) had pulmonary hemorrhage, 7.6% (116/1517) had severe intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL), 5.7% (87/1517) had necrotizing enterocolitis (NEC), and 2.0% (31/1517) had severe retinopathy of prematurity. The total and in-hospital mortality rates were 9.7% (169/1750) and 3.0% (45/1517), respectively. The top three diagnoses of death among those who had received complete treatment were sepsis, NRDS, and NEC. In 2009-2015, 1146 VLBW were enrolled and 895 infants received complete treatment. The proportions of apnea, IVH, and IVH stage ≥3/PVL, were higher in 2009-2015 compared with those in 2016-2021, while the proportions of NRDS and BPD were characterized by significant increases in 2016-2021. The total and in-hospital mortality rates were 16.7% (191/1146) and 5.6% (50/895) respectively in 2009-2015.Conclusion::Among VLBW infants born in 2016-2021, the total and in-hospital mortality rates were lower than those of neonates born in 2009-2015. Incidences of NRDS and BPD increased in 2016-2021, which affected the survival rates and long-term prognosis of VLBW.

Aim To investigate the synergistic sensiti-zation effect of saikosaponin D(SSD)combined with temozolomide(TMZ)on glioblastoma cells(GBM)and its molecular mechanism.Methods The sensitiv-ity of RG-2,U251 and LN-428 GBM cell lines to SSD and TMZ was analyzed by CCK-8 method combined with HE staining,and the optimal compatible concen-tration was screened.The effect of HE staining com-bined with Hoechst fluorescence staining on the prolif-eration of GBM cell line was detected by clonal forma-tion experiment.The autophagosome formation of GBM cells was observed by monodansylcadaverine(MDC)staining.The expression and distribution of endoplas-mic reticulum stress-related factors and apoptosis and autophagy proteins were detected by Western blot and ICC.Results The sensitivity order of GBM cells to TMZ was RG-2＞U251＞LN-428.The results of com-bined administration showed the synergistic inhibitory effect of SSD combined with TMZ on proliferation of GBM cell lines,which was confirmed by cell cloning formation experiment.Compared with the TMZ group,Hoechst fluorescence staining showed a significant in-crease in the number of nuclear bright staining in the combined administration group.MDC fluorescence staining showed that there were more dense green parti-cles in the cytoplasm of SSD/TMZ plus group than that of TMZ group.Western blot results showed that com-pared with TMZ group,the expression of ER stress markers GRP78,CHOP,p-PERK and ATF6 signifi-cantly increased in SSD/TMZ group(P＜0.05).The expressions of apoptosis proteins caspase-12,caspase-9,caspase-3,cleaved caspase-3,Bax and autophagy proteins LC3 and Beclin-1 significantly increased(P＜0.05),which were verified by ICC test.Conclusions SSD can cooperate with TMZ to inhibit the prolifera-tion of GBM cells and induce apoptosis and autophagy,and enhance the sensitivity of GBM cells to TMZ by ac-tivating endoplasmic reticulum stress pathway.

Pulmonary fibrosis is a diffuse interstitial lung disease with poor prognosis,and its pathogenesis has not been fully clar-ified.Lipid,as a key component of cell structure involved in signal transduction,plays an important role in maintaining lung function.More and more studies show that lipid changes are closely related to the progress of pulmonary fibrosis.This paper briefly reviews the pulmonary fibrosis disease,the research pro-gress of lipidomics in pulmonary fibrosis and the role of various lipids in pulmonary fibrosis.

Aim To investigate the effects of Ginkgo biloba extract(GBE)on vascular endothelial dysfunc-tion induced by chronic intermittent hypoxia(CIH)in rats and its related mechanisms.Methods The CIH rat model was established,and 50 and 100 mg·kg-1 GBE was administered by intragastric administration.The systolic blood pressure(SBP)of the tail artery was detected in each group.HE staining was used to detect the morphology of aorta tissue.DAF-FM DA staining and nitric reductase assay were used to detect NO levels.ELISA was used to detect serum ET-1,TNF-α and IL-6 levels.DHE staining was used to de-tect reactive oxygen species(ROS)levels of aortic tis-sue.Kits were used to detect the serum levels of MDA,SOD and GSH-Px.Western blot was used to detect the levels of VCAM-1,ICAM-1,nucleus Nrf2,HO-1 and NQO1 of aortic tissue.Results GBE sig-nificantly decreased the levels of SBP,ET-1,ROS,MDA,VCAM-1,ICAM-1,TNF-α and IL-6,and sig-nificantly increased the levels of NO,SOD,GSH-Px,nuclear Nrf2,HO-1 and NQO1 in CIH rats.GBE sig-nificantly improved the histomorphology of aorta in CIH rats.Conclusions GBE can improve vascular endo-thelial dysfunction and reduce blood pressure in CIH model rats.The mechanism may be related to the acti-vation of Nrf2/ARE pathway and the inhibition of oxi-dative stress and inflammation by GBE.