BACKGROUND:Observational studies have shown that intervertebral disc degeneration affects sedentary and physical activity levels;however,the causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration is unclear. OBJECTIVE:To explore the causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration using the Mendelian randomization method. METHODS:Five features associated with behavioral correlations in the Oswestry disability index score,including time spent watching TV,time spent on the computer,and light/moderate/vigorous physical activity,were selected from large-scale population-based genome-wide association studies,and instrumental variables were extracted for each of these behaviorally related features.Mendelian randomization analyses were performed in conjunction with the extraction of intervertebral disc degeneration as an outcome from the Finn Gen latest version 9 database.The results were analyzed using the inverse variance weighted,MR-Egger regression,simple mode,weighted mode,weighted median estimator,and regression model odds ratios(OR)and 95%confidence interval(CI)to assess the causal relationship between sedentary and physical activity levels in the Oswestry disability index scoring and intervertebral disc degeneration.Cochran's Q was used to test for heterogeneity,MR-Egger intercept to test for multiplicity,and leave-one-out to test the sensitivity of single nucleotide polymorphisms to the causal relationship between exposure factors and disc degeneration. RESULTS AND CONCLUSION:The results of the Mendelian randomization analysis using inverse variance weighted method showed a positive causal association between time spent watching TV/on the computer and the risk of intervertebral disc degeneration(OR=1.775,95%CI:1.418-2.221,P<0.001)/(OR=1.384,95%CI:1.041-1.839,P<0.001),an inverse causal association between light physical activity and the risk of intervertebral disc degeneration(OR=1.000,95%CI:0.999-1.000,P=0.020).MR-Egger intercept analysis indicated there was potential horizontal polytropy between light physical activity and intervertebral disc degeneration(P=0.005),while there was no horizontal pleiotropy between time spent watching TV,time spent on the computer and intervertebral disc degeneration(P=0.521,P=0.851).Cochran's Q analysis showed that heterogeneity was observed between time spent watching TV,time spent on the computer and intervertebral disc degeneration(P=3.33×10-11,P=0.001),and no significant heterogeneity was observed between light physical activity and intervertebral disc degeneration(P=0.186).Overall,there is a bidirectional causal relationship between sedentary and physical activity levels in the Oswestry disability index score and intervertebral disc degeneration,i.e.,not only does intervertebral disc degeneration affect sedentary and physical activity levels in the Oswestry disability index score,but sedentary and physical activity levels in the Oswestry disability index score also affect intervertebral disc degeneration.These findings add to the genetic evidence for a positive effect of light physical activity on intervertebral disc degeneration,indicate that moderate/vigorous physical activity shows no significant causal relationship with intervertebral disc degeneration,and expand the evidence base for sedentary behaviors such as prolonged time spent watching TV/on the computer as a risk factor for intervertebral disc degeneration.

BACKGROUND:Yougui Pill is a famous formula of the Chinese traditional medicine,which has good efficacy for lumbar disc herniation due to kidney yang insufficiency. OBJECTIVE:To investigate the potential targets and mechanism of action of Yougui Pill in the treatment of lumbar disc herniation by using network pharmacology and molecular docking technology,and verified by animal experiments. METHODS:(1)Network pharmacological analysis:We obtained the active ingredients and targets of Yougui Pill from TCMSP and other databases,collected genes related to lumbar disc herniation from GeneCards database,and took the intersection of the two for the topological analysis to derive the main active ingredients and core therapeutic targets.Gene ontology function analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using R software.(2)Molecular docking:Autodock and Pymol software were utilized for the prediction of molecular binding energy of TCM active ingredients to core therapeutic targets.(3)Animal experiments:Eighteen Sprague-Dawley rats were randomly divided into a control group,a degeneration group and a Yougui Pill group,with 6 rats in each group.A rat model of intervertebral disc degeneration was prepared by fiber puncture method in the degeneration and Yougui Pill groups.At 2 weeks after modeling,Yougui Pill was given by gavage in the Yougui Pill group,once a day for 2 consecutive weeks.The level of tumor necrosis factor-α in serum was detected by the ELISA method,and morphological changes of the annulus fibrosus and nucleus pulposus cells were observed using hematoxylin-eosin staining. RESULTS AND CONCLUSION:There were 90 active ingredients and 64 targets,and the main active ingredients were found to be quercetin,kaempferol,β-carotene,soybean flavonoid,and 4'-O-methylnyasol.The core targets of Yougui Pill for the treatment of lumbar disc herniation were interleukin 6,tumor necrosis factor-α,AKT1,interleukin 1B,and vascular endothelial growth factor A.Enrichment analysis revealed that the intersecting genes might be expressed through the interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,MAPK signaling pathway,PI3K-AKT signaling pathway,and other signaling pathways to improve intervertebral disc degeneration.The molecular docking test verified that quercetin,kaempferol,and β-carotene had strong binding ability to the core targets.Animal experiments showed that the level of serum tumor necrosis factor α in the degeneration group was higher than that in the control group(P<0.05),and the level of serum tumor necrosis factor α in the Yougui Pill group was lower than that in the degeneration group(P<0.05).Hematoxylin-eosin staining showed that the fibrous annulus of the intervertebral discs and the structure of the nucleus pulposus in the degeneration group were destroyed,and the number of nucleus pulposus cells was reduced;there was a tendency to reconstructing the fibrous annulus of the intervertebral discs in the Yougui Pill group,and the number of nucleus pulposus cells increased compared with the degeneration group.To conclude,Yougui Pill may treat lumbar disc herniation by improving disc degeneration through the effects of quercetin,kaempferol,beta-carotene and other key active ingredients on core targets such as tumor necrosis factor.

BACKGROUND:It has been found in recent observational studies that assessing localized fat mass is crucial in the evaluation of disc degeneration.Although obesity has been recognized as a risk factor for disc degeneration,the causal relationship between fat mass,which is a key factor in obesity,and intervertebral disc degeneration has been unclear in previous studies. OBJECTIVE:To investigate the causal risk factors of intervertebral disc degeneration associated with different distributions of fat mass,thereby enhancing the understanding of the pathogenesis of intervertebral disc degeneration and contributing to the development of preventive,therapeutic,and prognostic strategies. METHODS:Genetic markers associated with trunk and lower limb fat mass were extracted as instrumental variables from the publicly available IEU Open GWAS under the conditions of strong correlation and fulfillment of linkage disequilibrium.These markers were combined with the Mendelian randomization analysis to investigate the relationship between body fat and intervertebral disc degeneration.We used the latest version 9 database of FinnGen and assessed the results using several regression models,including inverse variance weighting,MR-Egger regression,simple mode,weighted mode,and weighted median estimator.We also assessed the heterogeneity of the genetic markers using Cochran's Q test,and multiplicity was assessed using the MR-Egger intercept test.Additionally,we used the leave-one-out method to determine the sensitivity of individual genetic markers to the causal effect of the exposure and outcome.The results were presented as odds ratios(OR)and 95%confidence intervals(CI). RESULTS AND CONCLUSION:The results from the inverse variance weighting method revealed that there was a positive causal relationship between trunk fat mass and the risk of developing intervertebral disc degeneration(OR=1.25,95%CI:1.15-1.35,P＜0.001).Additionally,there was an inverse causal relationship between bilateral lower limb fat mass and the risk of developing intervertebral disc degeneration(OR=0.7,95%CI:0.63-0.78,P＜0.001;OR=0.69,95%CI:0.62-0.76,P＜0.001).Furthermore,the MR-Egger intercept analysis did not detect any potential horizontal pleiotropy.No bias single nucleotide polymorphisms were detected,while heterogeneity tests were present,and the leave-one-out sensitivity analysis suggested reliable results.The results above demonstrate a positive causal relationship between trunk fat mass and intervertebral disc degeneration.As trunk fat mass increases,the risk of intervertebral disc degeneration rises.With an increase in both lower limb fat mass,the risk of intervertebral disc degeneration decreases.Fat content and distribution affects the risk of developing intervertebral disc degeneration and should be given more attention.

Objective To investigate the relationship between the central foveal thickness(CFT),ellipsoid zone(EZ)interruption ratio and best corrected visual acuity(BCVA)in patients with idiopathic epiretinal membranes(iERM).Methods A retrospective case-control study was conducted.The cluster sampling method was used to select 336 iERM patients(500 eyes)who underwent physical examinations in 9 community hospitals of the Kailuan Group from 2014 to 2018.Among them,215 were male(64.0％)and 121 were female(36.0％),with an average age of 31-89(66.4±8.8)years.According to the gass classification,these patients were divided into three groups:gass 0 group(201 patients,305 eyes),gass 1 group(75 patients,101 eyes),and gass 2 group(60 patients,94 eyes).Pearson correlation analysis was used to evaluate the correlation between BCVA(converted to logMAR visual acuity)and gass classification,EZ interruption ratio,CFT.Results The average BCVA(logMAR)and CFT of 500 eyes were 0.45±0.28 and(337.6±101.8)μm,re-spectively,with EZ interruption in 86 eyes(17.2％).There were statistically significant differences in BCVA(logMAR)(0.62±0.29,0.48±0.23,0.26±0.32),CFT[(283.20±79.30)μm,(335.50±84.50)μm,(394.00±135.60)μm],and EZ interruption ratio(2.6％,20.8％,60.6％)among gass 0,gass 1 and gass 2 groups(all P＜0.05).Pearson correlation analysis showed that there was no correlation between age and BCVA among different groups(r2=0.021,P=0.314);BCVA was positively correlated with CFT(r2=0.531,P=0.000),EZ interruption ratio(r2=0.304,P=0.000),and gass classification(r2=0.587,P=0.000).Conclusion The EZ interruption may occur in the early stage of iERM.BCVA is correlated with CFT,EZ interruption ratio and gass classification;the incidence of EZ interruption in gass 2 iERM signifi-cantly increases.

[ABSTRACT]OBJECTIVE To analyze the risk factors for relapse in patients with chronic rhinosinusitis with nasal polyps(CRSwNP)combined with asthm and provide favorable information for precise treatment and healthy prognosis of patients with CRSwNP combined with asthma.METHODS The clinical data of 161 patients with chronic rhinosinusitis with nasal polyps(CRSwNP)combined with asthm who underwent endoscopic surgery at the Department of Otolaryngology Head and Neck Surgery,Yantai Yuhuanding Hospital,affiliated to Qingdao University,from January 2016 to June 2021 were selected.Based on Lasso's Cox regression analysis and multifactorial Cox regression analysis,the associated risk factors were investigated,and the area under curve(AUC)was calculated to determine the performance of the model.Finally,the Kaplan-Meier(K-M)curves were plotted for the relevant influencing factors.RESULTS The Age[HR(95%CI):0.96(0.948-0.98),P<0.001],gender[HR(95%CI):1.94(1.21-3.14),P=0.006],tissue eosinophil percentage[HR(95%CI):1.01(1.01-1.02),P=0.004],and endoscopic nasal polyp score[HR(95%CI):0.86(0.78-0.96),P=0.005]were highly correlated with recurrence in patients with CRSwNP combined with asthma.Patients with CRSwNP combined with asthma had a higher likelihood of relapse after treatment when the tissue Eos%was>21.28%and the endoscopic nasal polyp score was>4.CONCLUSION The age,gender,tissue eosinophil percentage and endoscopic nasal polyp score are independent risk factors for disease recurrence in patients with CRSwNP combined with asthma.

Objective To analyze three-dimensional(3D)radiographic characterizations of bone island(BI)in jaw using cone-beam computed tomography(CBCT).Methods CBCT data from four thousand patients were selected,reconstructed and analyzed using NNT 10.0 software.The sagittal,coronal and axial planes were used to analyze the 3D radiographic characteristics of BIs,including the localization,shape,density,boundary,the relationship between BIs and tooth and bone cortex,diameter and anatomical structures and complications involved.Their relationship with gender were analyzed.Results A total of 803 people had BIs,with the prevalence rate of 20.08%,including 338 males with 389 BIs and 465 females with 526 BIs.Both males and females had a dominant BI,and the ratio between male and female was 1∶1.38,but the difference was not statistically significant(P＞0.05).The BIs of both male and female mostly occurred in the mandibular premolars and molars area,and appeared irregular in shape,dense and contact with lingual bone cortex.Mostly BIs were apical type and with unclear boundary.The mean maximum diameter of mesial/distal direction was greater than buccal/lingual direction(P＜0.05).The most commonly involved anatomy structure was the inferior alveolar neural canal,cortical infil-tration and mental foramen.Conclusion There are no significant differences between males and females in the three-dimensional image characteristics of BIs in Chinese populations.CBCT can accurately and comprehensively analyze the 3D radiographic characteris-tics of BI and its relationship with the surrounding teeth and bone.

OBJECTIVE To study material basis of Xianglian Pill(XLP)in vivo and in vitro using UPLC-Q-TOF-MS/MS technique,and to qualitatively analyze the main components of Xianglian Pill as well as the prototypical components and metabolites that were absorbed into the blood.METHODS A Thermo Accucore C18 column(2.1 mm×100 mm,2.6 μm)was used with 0.1%formic acid in water(A)-acetonitrile(B)as the mobile phase in a gradient elution mode,the column temperature was 40℃,and the flow rate was 0.4 mL·min-1 with the injection volume of 4 μL.The mass spectrometry information was collected by using the electros-pray ionization(ESI)ion source in the positive-negative ion scan mode.RESULTS By analyzing the precise relative molecular mass,retention times,secondary fragments and other mass spectrometry information of the components,and comparing them with the mass spectrometry information of the corresponding control products and relevant literature information,a total of 75 chemical compo-nents were finally identified in the extract of Xianglian Pill,including alkaloids,sesquiterpenoids,flavonoids,limonins and organic acids.In addition,16 prototypical components and 15 metabolites were identified in the plasma of the mice after the administration of the drug.Most of the prototypical components found in the plasma were alkaloids,and the metabolic pathways of these components in vivo were mainly hydroxylation,demethylation,reduction,hydrolysis,hydrogenation and glucuronidation.CONCLUSION The method can be used for the rapid identification of the external and internal components of Xianglian Pill,and its analytical results lay the foundation for further basic research on the pharmacological substances.

OBJECTIVE To enrich the polymethoxyflavonoid-rich fraction from Citri Reticulatae Pericarpium using D101 macro-porous resin,and further to analyse the chemical constituents using High-Performance Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry(HPLC-Q-TOF-MS).METHODS Citri Reticulatae Pericarpium extract was adsorbed on D101 macro-porous resin and then eluted with different concentrations of ethanol to enrich the polymethoxyflavonoid-rich fraction;the content of the major flavonoid components was determined by high-performance liquid chromatography(HPLC);and the components were further an-alysed by HPLC-Q-TOF-MS.RESULTS The established HPLC method for the simultaneous determination of seven flavonoids in Citri Reticulatae Pericarpium extract was accurate and reliable.The contents of compounds such as nobiletin and tangeritin were signifi-cantly increased in the polymethoxyflavonoid-rich fraction.Using high resolution mass spectrometry(HRMS),70 and 60 compounds were identified from the Citri Reticulatae Pericarpium extract and the polymethoxyflavonoid-rich fraction,respectively,with 53 polyme-thoxyflavonoids being detected in these two extracts.CONCLUSION The results of this study provide an experimental basis for fur-ther identification of the pharmacological substance basis of the polymethoxyflavonoids in Citri Reticulatae Pericarpium and the estab-lishment of quality control methods.

The emergence of anti-vascular endothelial growth factor (VEGF) therapy has reduced the overall incidence of blindness from ocular neovascular disease.However, frequent intravitreal injections of anti-VEGF therapy are required, which places a significant burden to patients and affects long-term benefits.The angiopoietin (Ang)/tyrosine kinase with immunoglobulin-like and endothelial growth factor-like domains (Tie) pathways are identified as potentially therapeutic regulators for ocular neovascular disease, with additional benefits over anti-VEGF-A therapy.For ocular neovascular diseases, three molecules targeting the Ang/Tie pathway have been studied in clinical trials and the data released, in which faricimab, a bispecific immunoglobulin G1 antibody targeting VEGF-A and Ang-2, entered phase Ⅲ studies and met primary clinical endpoints, and two dosing regimens with prolonged treatment intervals (12 and 16 weeks) of faricimab showed reliable efficacy.Overall, the regulation of Ang/Tie pathway provides a new treatment option for ocular neovascular diseases, and it is necessary to deeply understand the mechanism of action of the pathway and accumulate more clinical data in the future.

【Objective】 To develop a quick and accurate crossmatching test technology without the power equipment and additional reagents before blood transfusion, so as to improve the timeliness and safety of blood transfusion treatment in sudden situations as war or natural disasters. 【Methods】 The irregular antibodies quickly promote coagulants (QPC) were used as the reaction medium reagent. The 200 μL QPC were wrapped in the bursts bead and preset within different recess of the detection tubes. The bursts beads were squeezed with the reagent left in the well, then the blood samples were dropped in the main(recipient plasma: 200 μL, donor 3%—5% RBC: 100 μL) and secondary(donor plasma: 200 μL, recipient 3%—5% RBC: 100 μL)reaction grooves. The result interpretated by hand wrestling or 1 500 g centrifugation of 15 seconds. Meanwhile, the comparing experiments with the prior methods were implemented to evaluate the method’s reliability. 【Results】 The results of the bursting reagent, being stored at 37℃ for one week, were consistent with those of the freshly prepared cross-matching reagent, indicating that the bursting reagent was practical in the field and had good stability at normal temperature. No statistical difference between the sensitivity and the results of the microcolumn gel method was noticed by paired data t test (P>0.05). The parallel cross matching tests of 50 clinical samples were performed by microcolumn gel method and coagulant-bursting technique; the Kappa value was 0.973 2, and irregular antibodies were detected in 2 cases, with concordance rate at 100%, showing good consistency. 【Conclusion】 The improved method is simple and fast, and also safe and reliable for compatibility testing before blood transfusion, which is especially suitable for the field rescue of the wounded in wartime and sudden natural disasters, and is worthy of popularization.