Stroke, a major cerebrovascular disease, has high morbidity and mortality. Effective methods to reduce the risk and improve the prognosis are lacking. Currently, uric acid (UA) is associated with the pathological mechanism, prognosis, and therapy of stroke. UA plays pro/anti-oxidative and pro-inflammatory roles in vivo. The specific role of UA in stroke, which may have both neuroprotective and damaging effects, remains unclear. There is a U-shaped association between serum uric acid (SUA) levels and ischemic stroke (IS). UA therapy provides neuroprotection during reperfusion therapy for acute ischemic stroke (AIS). Urate-lowering therapy (ULT) plays a protective role in IS with hyperuricemia or gout. SUA levels are associated with the cerebrovascular injury mechanism, risk, and outcomes of hemorrhagic stroke. In this review, we summarize the current research on the role of UA in stroke, providing potential targets for its prediction and treatment.
Humans ; Uric Acid/metabolism* ; Stroke/drug therapy* ; Animals ; Hyperuricemia/drug therapy* ; Ischemic Stroke/blood* ; Biomarkers/blood*

Objective To investigate the mechanisms by which Porphyromonas gingivalis(P.gingivalis)promotes the malignant progression of oral squamous cell carcinoma(OSCC)through the recruitment of chemokine receptor 6-positive(CCR6+)regulatory T cells(Treg)in the tumor microenvironment(TME).Methods The Cancer Genome Atlas(TCGA)database was used to analyze the correlation between chemokine ligand 20(CCL20),CCR6,and Treg.The Treg enrichment index and the expression levels of interleukin(IL)-10 and tumor necrosis factor β1(TGF-β1)were assessed in the high CCR6 expression group of OSCC patients.C57BL/6 mice were randomly assigned to a control group and an experimental group(n=6 in each group).The control group received a single injection of 100 μL SCC7,a mice head and neck squamous carcinoma cell line,while the experimental group received a single injection of 100 μL mixture of SCC7 cells and P.gingivalis in the cheek.After two weeks,the mice were sacrificed,and immunohistochemistry was performed to assess the expression levels of CCR6 and forkhead box protein 3(FOXP3)in OSCC.Flow cytometry was performed to analyze the effects of P.gingivalis on OSCC malignant biological behavior,CCR6+Treg cells,and the immune microenvironment.Results Bioinformatics analysis revealed a correlation between CCL20,CCR6,and Treg(r=0.373,P＜0.0001).OSCC patients with high CCR6 expression showed higher Treg enrichment scores and increased IL-10 expression.Animal experiments showed that P.gingivalis promoted the increase in the tumor volume(mm3)(0.294±0.105 in the control group and 0.526±0.101 in the experimental group,P＜0.01)and mass(mg)(206.200±53.950 in the control group and 376.000±119.200 in the experimental group,P＜0.01)in mice with OSCC.Immunohistochemistry confirmed a correlation between CCR6 and FOXP3(r=0.659,P＜0.05),and P.gingivalis promoted the expression of CCR6 and FOXP3.Flow cytometry analysis showed that P.gingivalis increased the proportion of CCR6+Treg(％)(13.780±1.506 in the control group and 18.260±2.257 in the experimental group,P＜0.01)and decreased the proportion of CD8+T cells(％)(27.120±1.647 in the control group and 21.060±3.148 in the experimental group,P＜0.01)in OSCC,thereby promoting the formation of a immunosuppressive microenvironment.Conclusion P.gingivalis promotes the malignant progression of OSCC by recruiting CCR6+Treg cells to form an immunosuppressive TME.

BACKGROUND:For the replacement treatment of long-segment tracheal defects,although tissue engineering research has made some progress in recent years,it is still not perfect,and one of the biggest difficulties is that the hemodynamic reconstruction of the tracheal replacement cannot be achieved rapidly. OBJECTIVE:To preliminarily explore the potential of polycaprolactone scaffolds modified with exosome-loaded hydrogels to construct a rapidly vascularized tracheal substitute. METHODS:Exosomes were extracted from bone marrow mesenchymal stem cells of SD rats.After preparation of hyaluronic acid methacrylate solution,the exosome solution was mixed with hyaluronic acid methacrylate solution at a volume ratio of 1:1.Hyaluronic acid methacrylate hydrogels loaded with exosomes were prepared under ultraviolet irradiation for 5 minutes.The degradation of exosome-unloaded hydrogels and the controlled release of exosome-loaded hydrogels were detected.Polycaprolactone scaffolds were prepared by 3D printing.The pure hyaluronic acid methacrylate solution and the exosome-loaded hyaluronic acid methacrylate solution were respectively added to the surface of the scaffold.Hydrogel-modified scaffolds and exosome-modified scaffolds were obtained after ultraviolet irradiation.Thirty SD rats were randomly divided into three groups with 10 rats in each group and subcutaneously implanted with simple scaffolds,hydrogel-modified scaffolds and exosome-modified scaffolds,respectively.At 30 days after surgery,the scaffolds and surrounding tissues of each group were removed.Neovascularization was observed by hematoxylin-eosin staining and Masson staining and the expression of CD31 was detected by immunofluorescence. RESULTS AND CONCLUSION:(1)As time went by,the hydrogel degraded gradually,and the exosomes enclosed in the hydrogel were gradually released,which could be sustained for more than 30 days.The exosome release rate was faster than the degradation rate of the hydrogel itself,and nearly 20%of the exosomes were still not released after 30 days of soaking.(2)Under a scanning electron microscope,the surface of the simple polycaprolactone scaffold was rough.After hydrogel modification,a layer of gel was covered between the pores of the scaffold,and the scaffold surface became smooth and dense.(3)After 30 days of subcutaneous embedding,hematoxylin-eosin staining and Masson staining showed that more neovascularization was observed inside the scaffolds of the exosome-modified scaffold group compared with the hydrogel-modified scaffold group.The hydrogels on the scaffolds of the two groups were not completely degraded.Immunofluorescence staining showed that CD31 expression in the exosome-modified scaffold group was higher than that in the hydrogel-modified scaffold group(P<0.000 1).(4)These results indicate that hyaluronic acid methacrylate hydrogels can be used as controlled-release carriers for exosomes.The 3D-printed polycaprolactone scaffold modified by hyaluronic acid methacrylate hydrogel loaded with exosomes has good biocompatibility and has the potential to promote the formation of neovascularization.

Objective The DNA methylation microhaplotype(DMH)refers to the combination of multiple methylation sites within a very short range,and these haplotypes show wide diversity.We carried out screening and validation of age-related DMHs in mouse blood.Methods We initially constructed a theoretical dataset of DMHs based on the mouse reference genome.We then screened age-related DMHs by Spearman's rank correlation analysis,using high-throughput sequencing information for DNA methylation in mouse blood from a network database.Finally,cross-validation was performed using a validation dataset.Results A total of 6787 142 DMH sites were identified within 50 bp in the mouse genome,including 98.64%of single-digit CpG sites.A total of 5835 age-associated DMHs were screened in 58 mouse blood samples(|rho|＞0.5,P＜0.01),accounting for 0.086%of DMHs.Finally,we validated the top 100 age-associated DMHs with high correlation in 95 independent samples,Resultsing in 44 loci.Conclusions The age-associated DMHs screened in this study may be useful in future studies of apparent age prediction using mouse blood and in aging studies.

Objective To study the value of virtual touch tissue imaging quantification (VTIQ) and real-time elastography technology in the differential diagnosis of benign and malignant Thyroid Imaging Reporting and Data System (TI-RADS) 4 thyroid nodules. Methods The real-time elastography imaging and touch tissue imaging quantitative (VTIQ) image features of 110 patients (117 nodules) with TI-RADS 4 thyroid nodules were retrospectively analyzed. The real-time elastic technology was used to measure strain ratio (SR) of nodules. VTIQ technique was used to measure the shear wave velocity (SWV) of nodules. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the two methods alone and in combination were calculated using postoperative pathology as the gold standard. Then, the ROC curve was drawn, and the area under the curve (AUC) and the optimal cut-off value were obtained. Results There were 43 benign nodules and 74 malignant nodules in 117 thyroid nodules. The specificity, accuracy, positive predictive value, negative predictive value, the area under the ROC curve of the two technologies alone and in combination were 80.3% vs 86.7% vs 83.7%,72.5% vs 82.3% vs 84.2%,76.1% vs 84.6% vs 87.5%,73.3% vs 83.4% vs 84.5%,79.7% vs 85.5% vs 88.7%,0.786 vs 0.869 vs 0.881.According to the ROC curve, the optimal cut-off value of SR was 3.3 and the optimal cut-off value of VTIQ was 3.03 m/s. The Z values and P values of the two methods alone and in combination were (Z=1.95, 1.83, 1.03, all P>0.05), respectively. There was no difference statistically among the three methods. Conclusion The two techniques alone or in combination are valuable in the differential diagnosis of TI-RADS 4 thyroid nodules with similar diagnostic value in the three methods.

Objective: To investigate the efficacy of tyrosine kinase inhibitor (TKI) treatment on non-small cell lung cancer (NSCLC) patients with postoperative recurrence who harbored uncommon EGFR mutations, and discuss the relationship between TKI treatment and prognosis. Methods: A total of 39 relapsed NSCLC patients after surgery with EGFR uncommon mutations who were detected at Cancer Hospital, Chinese Academy of Medical Sciences between January 1999 and December 2013 were retrospectively analyzed in this study. Twenty patients were treated with EGFR-TKI after recurrence and 19 cases were not. The clinical characteristics of patients with EGFR uncommon mutations were evaluated, and the prognosis of TKI-treatment group and non-TKI treatment group was compared. Results: In 39 relapsed NSCLC patients with EGFR uncommon mutations, insertion mutations and point mutations were included. The highest frequency of EGFR uncommon mutation happened in exon 20 (20/39, 51.3%). A total of 13 uncommon point mutations were detected in exon 18, 20 and 21. The most frequent rare point mutations located in exon 21, and there were 7 different point mutation sites in exon 21. G719S/C/A mutation in exon 18 was the most common type of point mutation (14/25, 56.0%). Survival after postoperative recurrence in TKI treatment group was obviously better than that in non-TKI treatment group, the median time after recurrence were 44 months and 23 months, respectively (P=0.044). However, the postoperative overall survival showed no differences between two groups (48 months vs 43 months, P=0.129). Conclusion NSCLC patients with postoperative recurrence who harbored rare EGFR mutations should be treated with TKI agent.

Objective To determine whether a prophylactic tolterodine administration before surgical operation on non-urologic patients under general aneathesia can prevent the occurrence of catheter-related bladder discomfort (CRBD) ; and to assess patients’ tolerance to the symptoms as well as the impact on related consultation work of urologic surgeons.Methods One hundred and eighty cases of non-urology patients who need general aneathesia operations were divided into 2 groups:90 cases in tolterodine group and 90 in control group.The assessment of CRBD is categorized into 4 steps and statistics for adverse events ( dry mouth,dizzyness and facial flushing) was also conducted.A record of the patients’ needs for urologic surgical consultation during their reservation of catheter was also kept.SPSS 13.0 used in the statistical analysis of data in terms of X2 examination,where the divergence P ＜ 0.05 was regarded statisticly valid.Results 82 cases were followed up in the tolterodine group with a 24.4％ CRBD occurrence,which included 7.2％ shows moderate and severe symptoms,and there were also 23 cases with dry mouth ( 28.0％ ),4 cases with dizzyness (4.8％),13 cases with facial flussing ( 15.8％ ),and 1 case who needs further consultation (1.2％).In the 86 followed-up cases in control group,CRBD occurance rate was 54.7％,with 30.2％ showed moderate and severe symptoms,plus 2 cases suffered from severe consequences.Nine cases ( 10.5％) in control group requires further consultation ( X2 =19.499,P =0.000 ＜ 0.05 ).Conclusions A prophylactic tolterodine administration before surgery to the patients underwent general aneathesia can prevent the occurrence ofcatheter-related bladder discomfort (CRBD) and reduce the consultation work of urologic surgeons.Patients using tolterodine show a higher rate of adverse events,yet to which most patients can tolerate.