Objectives:To observe the incidence of residual shunt post patent foramen ovale(PFO)closure and the effect of PFO closure in these migraine patients at one year after PFO. Methods:This retrospective study included patients who underwent PFO closure for migraine in the Second Affiliated Hospital Zhejiang University School of Medicine from January 2019 to June 2022,patients were divided into the grade 0 shunt group(n=67),the grade Ⅰ shunt group(n=10),the grade Ⅱ shunt group(n=13)and the grade Ⅲ shunt group(n=16)according to the results of contrast transthoracic echocardiography(cTTE)at 1 year after PFO closure.The incidence of postoperative migraine attacks among different groups of patients were compared.The risk factors of residual shunt after PFO closure were explored. Results:The mean age of enrolled 106 patients with migraine was(35.80±11.70)years,of which 83 patients(78.30%)were female.One year after PFO closure,the migraine attack and rating scale were significantly decreased compared to baseline in the grade 0 shunt group,in the grade Ⅰ shunt group and in the grade Ⅱ shunt group(all P<0.05),but not in the grade Ⅲ shunt group(P>0.05).The rate of significant and complete migraine was significantly higher in the grade 0 shunt group(58.21%),in the gradeⅠ shunt group(60.00%),in the grade Ⅱ shunt group(69.23%)as compared to the grade Ⅲ shunt group(18.75%,P=0.02)at one year after PFO.The rate of grade 0 shunt after PFO closure in patients with the microvesicles appearing in≥6 cardiac cycles in resting state before operation was significantly lower than in patients with the microvesicles appearing within 6 cardiac cycles and no microvesicles in resting state(24.00%vs.83.87%vs.70.00%,P=0.04).Logistic multivariate regression analysis showed that patients with microvesicles appearing beyond 6 cardiac cycles in resting state were more likely to have residual shunts in postoperative cTTE compared to the patients with negative cTTE and microvesicles appearing within 6 cardiac cycles in the cTTE in resting state before operation(OR=0.06,95%CI:0.02-0.23,P<0.01;OR=0.014,95%CI:0.05-0.41,P<0.01). Conclusions:Migraine patients who underwent PFO closure and with grade 0 to grade Ⅱ residual shunt at one year after PFO are most likely to have significant remission of migraine,while the incidence of migraine remission is low in patients with grade Ⅲresidual shunt.The incidence of residual shunt after PFO closure is higher in patients with the microvesicles appearing in 6 cardiac cycles in resting state in the cTTE before operation than in patients with the microvesicles appearing within 6 cardiac cycles and no microvesicles.

Objective:To explore characteristics of intestinal flora in patients with rheumatoid arthritis complicated with inter-stitial lung disease(RA-ILD),to analyze its influencing factors,and to explore improvement of intestinal flora in patients with RA-ILD by different treatment methods.Methods:A total of 100 patients with RA-ILD who visited Shijiazhuang People's Hospital from June 2021 to June 2022 were selected as research objects,and 100 healthy patients in Shijiazhuang People's Hospital during same pe-riod were selected as healthy group.High throughput sequencing was performed on intestinal flora of two groups,OTU flora abundance and α-Diversity,β-diversity,flora distribution and LEfSe difference were analyzed.Another 100 patients with RA-ILD were randomly divided into group A(n=50)and group B(n=50).Group A was treated with leflunomide+nidanib or pifenidone,and group B was treated with leflunomide+nidanib or pifenidone+bifidobacterium triad.Improvement of intestinal flora in two groups after treatment was analyzed.Correlation analysis was used to determine correlation between changes of intestinal flora and clinical characteristics and indicators in RA-ILD patients.Results:OTU flora abundance,α-diversity and β-diversity in RA-ILD patients were lower than that of healthy people.Abundance of Intestinibacter in RA-ILD group was higher than that in healthy group,and abundance of Lactobacillus,Escherichia coli,Klebsiella,Candidatus saccharimonas,Odoribacter and Enterococcus in RA-ILD group were lower than that in healthy group.After treatment,flora structure of group A and group B was improved.Group B was closer to healthy population,and cu-rative effect was significantly better than that of group A.Integinibacter bacteria level was positively correlated with age,RA course,DAS28,CRP,RF and KL-6(P<0.05),and negatively correlated with DLCO(P<0.05).Lactobacillus level was negatively correlated with course of RA,DAS28,CRP,RF,IL-6(P<0.05),and positively correlated with VC(P<0.05);Shigella coli level was negtively correlatied with RA course,ILD course,DAS28,ESR,RF,TNF-α(P<0.05).Klebsiella level was positively correlated with VC and DLCO(P<0.05);Bacterial level of Candida saccharimonas was negatively correlated with DAS28,ESR,CRP,RF,IL-6,TNF-α(P<0.05)and positive correlated with DLCO(P<0.05);Odoribacter bacteria level was negatively correlated with DAS28,CRP,RF,IL-6 and KL-6(P<0.05),and positively correlated with VC(P<0.05);Enterococcus level was negatively correlated with course of RA,ILD,DAS28,ESR,RF and KL-6(P<0.05),while positively correlated with DLCO(P<0.05).Conclusion:Intestinal microflora abundance of RA-ILD patients is significantly lower than that of healthy people,and there aree significant differences in some microflora,which are closely related to clinical characteristics and indicators.Using of bifidobacterium triad in clinical treatment is helpful to improve intestinal flora of RA-ILD patients.

Purpose/Significance To introduce the knowledge graph technology in the field of electronic information into the study of traditional Chinese medicine(TCM)terminology,and to demonstrate the dialectical relationship between the therapeutic effects of TCM and its nature,flavor,meridians and TCM diseases in a vivid way.Method/Process The top-down ontology construction method is adopted to build the top-level structure of TCM ontology on the Protégé platform.Taking the 2020 edition of the Chinese Pharmacopoeia as the data source,the TCM information in the pharmacopoeia is split and extracted,and the information of each axis is sorted,disambiguated and nor-malized.With the help of the Protégé platform,entities and relationships are created,and the TCM triple data is output in RDF data for-mat.Finally,the Neo4j graph database is used to store and display the RDF data to form a systematic TCM knowledge graph.Result/Con-clusion It mainly realizes the construction of the knowledge graph of TCM in the pharmacopoeia,and fully reveals the complex knowledge system structure in the field of TCM through data statistical analysis,knowledge measurement and drawing of visual graphics.

Objective To understand the current situation of quality management and implementation of risk-based quality management in clinical trial institutions.Methods In the form of questionnaires,Questionnaire Star was used to create the questionnaire,which was sent to clinical trial organisations in all provinces and cities to fill in through emails and institutional WeChat groups.Results The questionnaire results from 123 clinical trial institutions from 25 provinces were included for analysis.The quality management status was as follows:104(84.6%)institutions of the main quality management mode were the internal quality control by GCP department.On average,each institution had 3、4 full-time staff for quality management,with an average of 1 full-time staff to manage 16.8 projects and 10.9 specialties.In the last three years,65(52.8%)institutions conducted training for researchers 2-3 times/year.Ninety-five(77.2%)institutions had established a clinical trial funding allocation system.Forty-nine(39.2%)institutions had established GCP informatization management system and 44(35.2%)institutions had established risk-based quality management model.In the case of coordination between the clinical trial institution and the sponsor,47(41.2%)institutions did not not aware of the sponsor's/CRO's quality management plan in their collaboration with the sponsor.Conclusion The surveyed institutions have weaknesses,such as insufficient dedicated personnel for quality management,low utilization rate of GCP information systems.The collaborative capacity between clinical trial institutions and sponsors needs to be improved,and the implementation rate of risk-based quality management is also low.

Electronic data management has the advantages of saving cost and research time and improving the data quality, which has gradually been the mainstream form of clinical data collection and management. It is important to improve the quality of Traditional Chinese Medicine (TCM) clinical researches. This paper introduces the function, general style, developing principles and processes, management and training of Standard Operating Procedure (SOP) for electronic clinical data management. The characteristics and difficulties of electronic data management of TCM clinical researches are discussed and suggested solutions are proposed in the end.

Objective:To explore the relationship of risk factors and clinical features to assessments of children with cerebral palsy (CP ) using a magnetic resonance imaging classification system (MRICS).Methods:Medical records of CP patients under 18 years old were reviewed retrospectively. Data including high-risk factors, cranial MRI results and clinical characteristics were collected. The cranial MRI results were classified according to the MRICS.Results:Of 1357 patients studied, 1112 (82%) had received cranial MRI scans. Among them, 962 (86.5%) showed MRI-identified brain abnormalities, 489 in the periventricular white matter. Subjects with different weeks of gestation, birth weights, delivery times, neonatal hypoxic-ischemic encephalopathy, and neonatal cerebral hemorrhage had significantly different MRI classifications according to the system. Premature birth, low birth weight and multiple births correlated with the incidence of white matter brain injury. Only 4 of the subjects with neonatal cerebral hemorrhage were classified as having normal brain structures using the MRICS. However, gender, birth method, and pathological jaundice had no significant relationship with MRICS ratings. Significant differences in MRICS classifications were observed between patients with different CP subtypes, gross motor function scores, as well as with or without epilepsy, speech or language impairment. But degrees of mental retardation were not significantly related with MRICS classifications.Conclusion:MRICS classifications relate closely with risk factors and the clinical characteristics of CP patients. The system can play an important role in finding pathogenesis and predicting clinical outcomes. It is worthy of applying and promoting in the clinic.

Objectives To study the predictive value of Toll-like receptors 3,4(TLR3,TLR4),fructosamine(FMN)and glycated hemoglobin A1c(HbA1c)in the in-stent restenosis and re-occlusion after primary percutaneous coronary intervention(PCI)in patients aged 70-85 years with old myocardial infarction.Methods 51 patients aged 70-85 years with in-stent restenosis after primary PCI from Jan 2007 to Sep 2016 were selected.Serum level changes in TLR3,TLR4 were detected by flow cytometry.The levels of FMN and HbA1c were tested by colorimetric endpoint reaction and high-pressure liquid chromatography respectively.Results The levels of TLR3,TLR4,FMN and HbA1c were gradually elevated along with the increases of artery numbers(0,1,2,>2)and percentage(0%,70-89%,90-99%,100%)of in-stent restenosis,LVEF(%)decrease and NYHA(Ⅰ,Ⅱ,Ⅲ,Ⅳ)increase(all P<0.01).The examples of data were selected in the following groups of artery numbers(0,1,2,>2)of in-stent restenosis in TLR3,and group of percentage(0%,70-89%,90-99%,100%)in the in-stent restenosis in TLR4,group of LVEF(%)in FMN,and group of NYHAⅠ,Ⅱ,Ⅲ,Ⅳ in HbA1c(%)(all P<0.01).The levels of TLR3(%)in artery numbers of restenosis(0,1,2,>2)groups were(7.6±0.5),(18.9±0.6),(32.0±0.9),(51.3±0.8),respectively(all P<0.01).The levels of TLR4(%)in the in-stent restenosis percentage(0%,70-89%,90-99%,100%)groups were(10.5±7.0),(20.1±7.2),(33.3±9.7),(69.0±11.3%)respectively(all P<0.01).The levels of FMN(mmol/L)in LVEF[(49~59%),(37~48%),(25~36%)]groups were(0.6±0.4),(9.4±0.6),(18.1±0.8),respectively(all P<0.01).And the level of HbA1c(%)in groups of NYHA Ⅰ,NYHA Ⅱ,NYHA Ⅲ,NYHA Ⅳ were(6.1±0.4),(5.9±0.6),(8.9±0.9),(12.0±0.8),respectively(all P<0.01).Conclusions Serum level changes in TLR3,TLR4,FMN and HbA1c may become the new indicators to forecast the degree of in-stent restenosis in very old patients with old myocardial infarction after primary coronary intervention.

In this article, a new TCM clinical trial of phaseⅢ was served as an example of application of Clinical Data Interchange Standards Consortium (CDISC). It briefly introduced seven data acquisition modules commonly used in clinical research of new traditional Chinese medicine, namely demographics, subject characteristic, clinical event, medical history, questionnaire, laboratory inspection and adverse event. It also introduced the process of transferring the above modules to Study Data Tabulation Models (STDM), and discussed the feasibility and some issues that required attention of CDISC application in clinical research of new traditional Chinese medicine.

Objective To study the changes in expression of high-sensitivity C-reactive protein (hsCRP),glutathione S-transferase Pi(GSTPi)and annexin A5 (AnxA5)in elderly patients with old myocardial infarction and the clinical significance.Methods Serum levels of GSTPi and AnxA5 were measured by ELISA and the level of hs-CRP was measured by immunoturbidimetry in elderly patients with old myocardial infarction (n =185)from December 2012 to November 2015.Results Along with the increasing coronary artery stenosis,GSTPi level was decreased and AnxA5/hs-CRP levels were increased in elderly patients with old myocardial infarction.In comparison between coronary artery stenosis ＞ 95％ group versus stenosis of 55％-65％ group,GSTPi was(190.0±37.0)μg/L vs.(289.0 ±86.0)μg/L,AnxA5 was(33.9±4.0)μg/L vs.(8.1 ± 2.9) μg/L,and hs-CRP was (15.3 ± 1.3) mg/L vs.(5.9 ± 0.8) mg/L with statistically significant differences(all P＜0.01).There were significant differences between LVEF 30％ group[GSTPi(198.0±39.0) μg/L,AnxA5(38.9±5.1)μg/L and hs-CRP(17.9± 1.9)mg/L]and LVEF 40％-54％ group[GSTPi(219.0± 61.0)μg/L,AnxA5 (12.9±3.9)μg/L and hs-CRP(10.1 ± 1.0) mg/L] (all P＜0.01).There were significant differences between NYHA Ⅳ group [GSTPi (171.0 ± 43.0) μg/L,AnxA5 (18.1 ± 5.0) μg/L and hs-CRP (16.9±2.1)mg/L]and NYHAⅠgroup[GSTPi(295.0±91.0)μg/L,AnxA5(7.3±3.1)μg/L and hs-CRP (7.8± 1.3)mg/L](all P＜0.01).Conclusions The expression of GSTPi,AnxA5 and hs-CRP in elderly patients with old myocardial infarction may become the new indicators to forecast the degrees of coronary artery stenosis and heart failure.

Objective To explore the correlation of mimecan/osteoglycin withnuclear factor koppa B(NF-κB) and P53 in peripheral arterial disease (PAD) and PAD combined with type 2 diabetes in the elderly.Methods 120 patients with PAD and 60 healthy controls were enrolled in this study.PAD patients were divided into PAD group (n=60) and PAD combined with type 2 diabetes group (n =60) according to clinical diagnostic criteria.Patients in PAD group were divided into class Ⅰ (n=15),class Ⅱ (n=15),class Ⅲ (n=15) and class Ⅳ (n=15),and patients in PAD combined with type 2 diabetes group were divided to class Ⅰ (n=14),class Ⅱ (n=15),class Ⅲ (n=16) and class Ⅳ (n=15) according to Fontaine's classification.The levels of NF-κB,P53 and mimecan in peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA).Results The levels of NF-κB,P53 and mimecan were significantly increased in PAD combined with type 2 diabetes group as compared with PAD and control groups [NF-κB..(32.8±5.3) mg/L vs.(19.8±4.2) mg/L,(26.3 ±4.8) mg/L; P53:(3.4±1.3) mg/Lvs.(2.5±1.1) mg/L,(1.4±0.8) mg/L; mimecan:(16.4 ±0.8) mg/L vs.(10.3±0.8) mg/L,(4.8±0.6) mg/L; all P＜0.05].There were significant differences in the levels of NF-κB,P53 and mimecan in class Ⅰ,class Ⅱ,class Ⅲ and class Ⅳ in PAD group [NF-κB:(20.3±3.1) mg/L,(24.5±3.4) mg/L,(28.2±4.6) mg/L and (34.2±5.3) mg/L; P53:(2.2 ±1.8) mg/L,(2.6±1.8) mg/L,(3.3±1.9) mg/L and (3.7±2.7) mg/L;mimecan (8.9±2.6) mg/L,(12.4±1.8) mg/L,(15.6±1.5) mg/L and (17.7±1.6) mg/L; all P ＜0.05].There were significant differences in the levels of NF-κB,P53 and mimecan in class Ⅰ,class Ⅱ,class Ⅲ and class Ⅳ in PAD group combined with type 2 diabetes group [NF-κB:(25.5±4.2) mg/L,(28.8±3.7) mg/L,(33.4±5.6) mg/L and (38.5±4.7) mg/L; P53:(2.5±1.1)mg/L,(2.9±1.0)mg/L,(3.7±1.2)mg/L and(4.6±1.3)mg/L; mimecan:(11.7±2.4)mg/L,(14.9± 1.8)mg/L,(17.4±2.5)mg/L and(20.7±2.8)mg/L; all P＜0.05].The levels of NF-κB,P53 and mimecan was increased with the aggravation of PAD (all P＜0.05).Conclusions The increased levels of NF-κB and P53 are correlated with the increase in mimecan level and Fontaine's classification.