Objective To investigate the effects of low background radiation environments in deep underground settings on the biological behavior of NP69 human nasopharyngeal epithelial cells(NP69 cells)and the underlying molecular mechanisms.Methods A parallel control experimental design was adopted and NP69 cells were synchronously cultured in settings of three underground depths at the China in situ Deep-Underground Facility&Life Observatory(DeUFO)—ground level(DeUFO-0 m),1 000 m underground(DeUFO-1 000 m),and 1 500 m underground(DeUFO-1 500 m).Changes in cell proliferation and migration capabilities were assessed using the Cell Counting Kit-8(CCK-8)assay and scratch assay,respectively.High-throughput RNA sequencing(RNA-Seq)was performed to identify differentially expressed genes(DEGs).Functional annotation and pathway enrichment analysis of the DEGs were performed using the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.Results CCK-8 assay revealed that,after 72 h of culture,the absorbance value of the DeUFO-0 m group was 1.35 times and 1.27 times those of the those of the DeUFO-1 000 m and DeUFO-1 500 m groups,respectively(both P<0.000 1).After 96 h of culture,the absorbance value of the DeUFO-0 m group was 1.52 times and 1.41 times those of the DeUFO-1 000 m and DeUFO-1 500 m groups,respectively(both P<0.000 1).Colony formation assays revealed that the number of cell colonies in the DeUFO-0 m group was 1.59 times and 1.27 times those in the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.001).The scratch assay revealed that the 36-hour wound healing rate of the DeUFO-0 m group was 2.22 times and 4.00 times those of the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.000 1).Transwell assays revealed that the number of migrating cells in the DeUFO-0 m group was 2.08 times and 2.56 times those in the DeUFO-1 000 m group and DeUFO-1 500 m group,respectively(both P<0.000 1).Transcriptome sequencing analysis revealed consistent upregulation of CELF2,CELF4,CGB8,GRHL2,and DMRTA2 genes in the DeUFO-1 000 m and DeUFO-1 500 m groups.Pathway enrichment analysis indicated significant enrichment of extracellular matrix(ECM)remodeling-associated pathways and gene expression regulation pathways in the experimental groups(false discovery rate[FDR]<0.05).Conclusion The low background radiation environment in deep underground settings suppresses the proliferation and migration activities of NP69 cells by mediating ECM remodeling and post-transcriptional regulatory mechanisms through the regulation of target genes such as the CELF family.This study provides experimental evidence for establishing a dose-response relationship between environmental radiation and cellular effects.

Objective To compare the clinical efficacy and safety of lumbar intervertebral space implantation with single and two fusion devices in treatment of lumbar instability under intervertebral foraminoscopy.Methods 101 patients(101 vertebral bodies)diagnosed with L4,L5 or S1 segment Ⅰ° to Ⅱ° spondylolisthesis from January 2019 to June 2022 were enrolled and the patients were randomly divided into group A(single fusion device group)and group B(double fusion devices group)by intervertebral foraminoscopy.Among of them,there were 51 cases of vertebral spondylolisthesis in group A and 50 cases of vertebral spondylolisthesis in group B.The patients were followed up at 1 week,1 month,6 months,9 months and 15 months after surgery,and the differences in spondylolisthesis distance,intervertebral space height,intervertebral space fusion,vertebral sedimentation rate,lumbar pain visual analogue scale(VAS)and lumbar Oswerry disability index(ODI)between the two groups were compared.Results All the 101 patients were followed up throughout the whole process,and there were no significant differences in operation time,intraoperative blood loss,and postoperative drainage between the two groups(P＞0.05),and the VAS was(7.32±0.57)in group A and(7.14±0.61)in group B one week after operation,there was no significant difference between the two groups(P＜0.05).At 6 months after surgery,the ODI of group A was(27.44±9.52)%and group B was(21.89±8.46)%,and there was no significant difference between the two groups(P＞0.05).And at 6,9 and 15 months follow-up,the fusion rates of group A were 11.76%,68.63%and 90.20%,respectively,and the fusion rates of group B were 18.00%,80.00%and 96.00%,respectively,and there was significant difference between the two groups(P＜0.05).At 15 months postoperative follow-up,the intervertebral space height of group A(0.45±0.07)cm was significantly smaller than that of group B(0.58±0.06)cm,and the difference was statistically significant(P=0.038).There was no significant difference between group A and group B(0.33±0.18)mm and(0.28±0.21)mm(P=0.079)of spondylolisthesis distance.Conclusion Implantation of the double fusion devices can provide more contact area and better stability,shorten the vertebral fusion time,increase the vertebral fusion rate,and reduce the occurrence of vertebral settlement.It is worthy of clinical promotion and application.

Objective To investigate the association between extensive perivascular space(EPVS)burden in different locations and ischemic stroke(IS),its subtypes,and transient ischemic attack(TIA)through Mendelian randomization(MR)analysis.Methods The summary data from large-scale Genome-wide Association Studies(GWAS)and various MR methods were employed.We applied multivariable MR to mitigate potential confounding factors and conduct sensitivity analyses to enhance result robustness.Subsequently,meta-analysis was utilized to integrate causal relationships between EPVS burden in different locations and IS from various sources.Additionally,reverse MR was employed to observe the impact of various IS types on EPVS burden.Finally,linkage disequilibrium score regression was conducted to assess genetic correlations between exposures and outcomes.Results EPVS burden in both the white matter(OR=1.12,95％CI:1.01-1.25;P=0.04)and basal ganglia(OR=1.57,95％CI:1.30-1.89;P＜0.01)are significant risk factors for IS.EPVS burden in the basal ganglia is also a risk for IS(small-vessel)(OR=4.56,95％CI:2.57-8.27;P=5.95× 10-7).After IS and TIA there seems to be a potential increase in extensive basal ganglia perivascular space burden.Conclusions Extensive white matter perivascular space burden and extensive basal ganglia perivascular space burden may serve as important indicators to predict IS.

Objective To compare the clinical efficacy and safety of lumbar intervertebral space implantation with single and two fusion devices in treatment of lumbar instability under intervertebral foraminoscopy.Methods 101 patients(101 vertebral bodies)diagnosed with L4,L5 or S1 segment Ⅰ° to Ⅱ° spondylolisthesis from January 2019 to June 2022 were enrolled and the patients were randomly divided into group A(single fusion device group)and group B(double fusion devices group)by intervertebral foraminoscopy.Among of them,there were 51 cases of vertebral spondylolisthesis in group A and 50 cases of vertebral spondylolisthesis in group B.The patients were followed up at 1 week,1 month,6 months,9 months and 15 months after surgery,and the differences in spondylolisthesis distance,intervertebral space height,intervertebral space fusion,vertebral sedimentation rate,lumbar pain visual analogue scale(VAS)and lumbar Oswerry disability index(ODI)between the two groups were compared.Results All the 101 patients were followed up throughout the whole process,and there were no significant differences in operation time,intraoperative blood loss,and postoperative drainage between the two groups(P＞0.05),and the VAS was(7.32±0.57)in group A and(7.14±0.61)in group B one week after operation,there was no significant difference between the two groups(P＜0.05).At 6 months after surgery,the ODI of group A was(27.44±9.52)%and group B was(21.89±8.46)%,and there was no significant difference between the two groups(P＞0.05).And at 6,9 and 15 months follow-up,the fusion rates of group A were 11.76%,68.63%and 90.20%,respectively,and the fusion rates of group B were 18.00%,80.00%and 96.00%,respectively,and there was significant difference between the two groups(P＜0.05).At 15 months postoperative follow-up,the intervertebral space height of group A(0.45±0.07)cm was significantly smaller than that of group B(0.58±0.06)cm,and the difference was statistically significant(P=0.038).There was no significant difference between group A and group B(0.33±0.18)mm and(0.28±0.21)mm(P=0.079)of spondylolisthesis distance.Conclusion Implantation of the double fusion devices can provide more contact area and better stability,shorten the vertebral fusion time,increase the vertebral fusion rate,and reduce the occurrence of vertebral settlement.It is worthy of clinical promotion and application.

Objective To investigate the association between extensive perivascular space(EPVS)burden in different locations and ischemic stroke(IS),its subtypes,and transient ischemic attack(TIA)through Mendelian randomization(MR)analysis.Methods The summary data from large-scale Genome-wide Association Studies(GWAS)and various MR methods were employed.We applied multivariable MR to mitigate potential confounding factors and conduct sensitivity analyses to enhance result robustness.Subsequently,meta-analysis was utilized to integrate causal relationships between EPVS burden in different locations and IS from various sources.Additionally,reverse MR was employed to observe the impact of various IS types on EPVS burden.Finally,linkage disequilibrium score regression was conducted to assess genetic correlations between exposures and outcomes.Results EPVS burden in both the white matter(OR=1.12,95％CI:1.01-1.25;P=0.04)and basal ganglia(OR=1.57,95％CI:1.30-1.89;P＜0.01)are significant risk factors for IS.EPVS burden in the basal ganglia is also a risk for IS(small-vessel)(OR=4.56,95％CI:2.57-8.27;P=5.95× 10-7).After IS and TIA there seems to be a potential increase in extensive basal ganglia perivascular space burden.Conclusions Extensive white matter perivascular space burden and extensive basal ganglia perivascular space burden may serve as important indicators to predict IS.

Objective:To investigate the effect of apoptosis-associated protein kinase-like 1 (DAPL1) hypomethylation on prognosis of lung cancer patients with epidermal growth factor receptor gene exon 19 deletion (EGFR Del19) mutation.Methods:The clinicopathological data of lung cancer patients in databases of genomic data sharing (GDC) TCGA lung adenocarcinoma, TCGA lung adenocarcinoma, and TCGA lung cancer were collected to analyze the effect of DAPL1 methylation level on the prognosis of patients with EGFR Del19 mutation. Linear regression model was used for correlation analysis, Kaplan-Meier method was used to draw the survival curve, and the difference of survival curve between the two groups was tested by Log rank.Results:In GDC TCGA lung adenocarcinoma, TCGA lung adenocarcinoma and TCGA lung cancer databases, the 5-year survival rates of lung cancer patients with high DAPL1 expression (31.9%, 27.5% and 33.0%, respectively) were higher than those with low DAPL1 expression (11.0%, 11.6% and 13.8%, respectively). The differences were statistically significant ( P=0.006, 0.028 and 0.025, respectively). The median expression levels of DAPL1 in patients with EGFR Del19 mutation (12.8, 2.75 and 2.9, respectively) were higher than those in patients with other EGFR mutations (11.6, 1.75 and 1.8, respectively, P<0.05). In TCGA lung adenocarcinoma and TCGA lung cancer database, the 5-year survival rate of lung cancer patients with lower DAPL1 methylation levels (22.4% and 16.4%, respectively) were higher than those of lung cancer patients with higher DAPL1 methylation levels (15.1% and 14.2%, respectively), with statistical significance ( P<0.05). The expression level of DAPL1 was positively correlated with the EGFR mutant subtype ( r=0.909, P<0.05), and negatively correlated with DNA methylation ( r=-0.891, P<0.05). The expression of DAPL1 in lung cancer patients was regulated by DNA methylation, which affected the prognosis of lung cancer patients. Conclusion:High DAPL1 expression, or hypomethylation, is associated with lung cancer EGFR Del19 mutation subtype, and DAPL1 hypomethylated lung cancer patients have longer overall survival.

Objective:To investigate the effect of apoptosis-associated protein kinase-like 1 (DAPL1) hypomethylation on prognosis of lung cancer patients with epidermal growth factor receptor gene exon 19 deletion (EGFR Del19) mutation.Methods:The clinicopathological data of lung cancer patients in databases of genomic data sharing (GDC) TCGA lung adenocarcinoma, TCGA lung adenocarcinoma, and TCGA lung cancer were collected to analyze the effect of DAPL1 methylation level on the prognosis of patients with EGFR Del19 mutation. Linear regression model was used for correlation analysis, Kaplan-Meier method was used to draw the survival curve, and the difference of survival curve between the two groups was tested by Log rank.Results:In GDC TCGA lung adenocarcinoma, TCGA lung adenocarcinoma and TCGA lung cancer databases, the 5-year survival rates of lung cancer patients with high DAPL1 expression (31.9%, 27.5% and 33.0%, respectively) were higher than those with low DAPL1 expression (11.0%, 11.6% and 13.8%, respectively). The differences were statistically significant ( P=0.006, 0.028 and 0.025, respectively). The median expression levels of DAPL1 in patients with EGFR Del19 mutation (12.8, 2.75 and 2.9, respectively) were higher than those in patients with other EGFR mutations (11.6, 1.75 and 1.8, respectively, P<0.05). In TCGA lung adenocarcinoma and TCGA lung cancer database, the 5-year survival rate of lung cancer patients with lower DAPL1 methylation levels (22.4% and 16.4%, respectively) were higher than those of lung cancer patients with higher DAPL1 methylation levels (15.1% and 14.2%, respectively), with statistical significance ( P<0.05). The expression level of DAPL1 was positively correlated with the EGFR mutant subtype ( r=0.909, P<0.05), and negatively correlated with DNA methylation ( r=-0.891, P<0.05). The expression of DAPL1 in lung cancer patients was regulated by DNA methylation, which affected the prognosis of lung cancer patients. Conclusion:High DAPL1 expression, or hypomethylation, is associated with lung cancer EGFR Del19 mutation subtype, and DAPL1 hypomethylated lung cancer patients have longer overall survival.

Objective:To investigate the clinical application of cervix-uterine internal target volume (ITV) in volume-modulated arc therapy (VMAT) for cervical cancer under different bladder filling conditions, aiming to obtain more accurate planning target volume (PTV).Methods:Sixty-two patients with cervical cancer receiving radiotherapy rather than surgery were selected and randomly divided into the study ( n=31) and control groups ( n=31). In the study group, individualized ITV, PTV and PTV margin were obtained under three bladder filling status by localization CT scan to compare the VMAT. The target area and organs at risk (OARs) within the target area were statistically compared between two groups. The target missing rate in CBCT, adverse events and short-term efficacy of radiotherapy were analyzed in two groups. Results:There was no significant difference in the volume of target area and OARs in the target area between two groups (both P>0.05). In the study group, the target missing rate and target missing volume were significantly lower compared with those in the control group (both P<0.05). There was no significant difference in the incidence of acute radiation-induced adverse events between two groups ( P>0.05). The 1-, 2-year overall survival and progress-free survival did not significantly differ between two groups (all P>0.05). One patient in the study group had uterine recurrence and 2 cases in the control group. Conclusion:Application of individualized cervix-uterine ITV and PTV in definitive VMAT under different bladder filling conditions can improve the accuracy of target area contouring and improve the local control rate in cervical cancer patients.

Cervicitis is a common infectious disease of female reproductive system. As a portal to the uterus and pelvic cavity, cervical tube has a certain protective effect. When the inflammation spreads upward, it can not only affect the normal pregnancy and cause many adverse pregnancy outcomes, such as infertility, abortion, premature birth, premature rupture of membranes and reproductive failure, but also can cause neonatal infection, even neonatal death. The clinical treatment of cervicitis can improve pregnancy, mainly about physical therapy and drug therapy, but the prognosis and potential impact of various intervention methods on female cervical infection are not the same. Therefore, it is particularly critical to adopt active and appropriate treatment. This paper discusses the effects of cervicitis and different treatment methods on pregnancy outcome and assisted reproduction technology as to provide reference for the treatment of related diseases in clinic.

Cervicitis is a common infectious disease of female reproductive system. As a portal to the uterus and pelvic cavity, cervical tube has a certain protective effect. When the inflammation spreads upward, it can not only affect the normal pregnancy and cause many adverse pregnancy outcomes, such as infertility, abortion, premature birth, premature rupture of membranes and reproductive failure, but also can cause neonatal infection, even neonatal death. The clinical treatment of cervicitis can improve pregnancy, mainly about physical therapy and drug therapy, but the prognosis and potential impact of various intervention methods on female cervical infection are not the same. Therefore, it is particularly critical to adopt active and appropriate treatment. This paper discusses the effects of cervicitis and different treatment methods on pregnancy outcome and assisted reproduction technology as to provide reference for the treatment of related diseases in clinic.