Objective To investigate the clinical value of substitute popliteal vein valve operation (SPVSO) for primary lower limb deep vein insufficiency(DVIS). Methods The clinical data of 859 cases(907 legs) of DVIS who underwent SPVSO in the past 10 years in our hospital were analyzed retrospectively. Results Symptoms of edema and fatigue distinctly reduced or disappeared after the operation.Pigmentation in the lower portion of the leg began to disappear in 1 week, and nearly or totally disappeared within 2 weeks after the operation.Ulcer in the lower portion of the leg recovered three weeks after the operation. Patients were followed up for 6 to 120 months. The effective rate within 60 months was 96.8%, and the effective rate over 60 months was 87.2%. Conclusions The curative effect of SPVSO on primary deep vein insufficiency of lower extremity is definite and it is worthy to be clinical practice.

Objective:To summarize our clinical experience in the treatment of aortic root aneurysm by aortic valve sparing root replacement.Methods:From May 2017 to October 2019, a total of 20 patients with aortic root aneurysm underwent aortic valve sparing root replacement by reimplantation method. There were 17 males and 3 females, with an average age of(35.6±15.8) years(12-63 years). There were 11 cases of Marfan syndrome, 5 cases of bicuspid aortic valve, and 1 case of redo operation. The preoperative diameter of ascending aorta was(40.6±9.7)mm, the diameter of aortic sinus was(52.2±9.2)mm, and the diameter of aortic valve ring was(27.1±3.6)mm. There were 10 cases of no or mild regurgitation, 5 cases of moderate regurgitation and 5 cases of severe regurgitation. In the whole group of patients, the root replacement of aortic valve was retained by reimplantation, and the artificial graft were selected as: 26, 28 and 30mm straight vessels, 1, 3 and 6 cases, respectively, 26 and 28mm artificial graft with valsalva sinus, 4 and 6 cases, respectively. During the operation, aortic valve cusp repair was performed in 6 cases, such as plication of the free margin( 4 cases), decalcification(1 case) and raphe release(1 case).Results:None of the patients died in hospital or underwent rethoracotomy for hemostasis. During the operation, the duration of CPB time was(171.0±25.6) minutes and the duration of cross-clamp time was(134.0±23.2) minutes. There were 12 cases of aortic valve regurgitation and 8 cases of mild regurgitation. The mean follow-up was(15.1±9.8) months(4-33 months). During the follow-up period, there were 2 cases with moderate aortic regurgitation no need reoperation, while the rest of the patients had no or mild regurgitation. There are no patients undergoing reoperation. During the follow-up, 1 patient suffered coronary artery embolism in left circumflex artery and recovered after medicine treatment.Conclusion:Reimplantation with aortic valve sparing root replacement is safe and effective in the treatment of aortic root aneurysm, and the early and mid-term follow-up results are satisfactory, which can avoid anticoagulation-related complications and is suitable for young patients.

Objective To investigate the risk factors for clopidogrel resistance (CR) in patients with ischemic stroke.Methods Turbidimatry was used to measure the platelet aggregation rate changes after the patients with acute ischemic stroke taking 75 mg of clopidogrel per day for 10-14 days.The patients were divided into either a CR or a clopidogrel sensitivity (CS) group according to the platelet aggregation rate changes.The demographic and clinical data of both groups were compared.Multivariate logistic regression analysis was used to identify the independent risk factors for CR.Results A total of 147 patients with acute ischemic stroke were included,42 of them (28.57％ ) were in the RC group and 105 (71.43％) were in the CS group.The proportion of patients in diabetes (54.76％ vs.11.43％ ;x2 =31.054,P =0.000),the history of transient ischemic attack (TIA) (80.95％ vs.26.67％ ;x2 =36.251,P=0.000) or percutaneous coronary intervention (PCI) (26.19％ vs.3.81％;x2 =16.400,P=0.000),taking calcium channel blocker (CCB) (83.33％ vs.54.29％ ;x2 =10.810,P =0.001 ),angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) (66.67％ vs.42.86％;x2 =6.803,P=0.009),and proton pump inhibitor (47.62％ vs. 14.29％;x2 =18.375,P =0.000) in the CR group,as well as the levels of plasma total cholesterol (TC),glucose,and glycated hemoglobin were significantly higher than those in the CS group.Multivariate logistic regression analysis showed that diabetes (odds ratio [ OR] 13.711,95％ confidence interval [ CI] 1.667 - 112.784; P =0.015),increased TC level (OR 2.828,95％CI 1.574 - 5.080; P =0.001),previous history of TIA (OR16.627,95％ CI 4.691 - 58.934; P =0.000),and long-term taking CCB (OR 4.147,95％ CI 1.053 - 16.332;P =0.042),and ACEI/ARB (OR 4.841,95％ CI 1.539 - 15.231; P =0.007) were the independent risk factors for CR.Conclusions CR in patients with ischemic stroke is associated with a variety of factors,in which diabetes,increased TC,as well as long-term taking CCB and ACEI/ARB are the independent risk factors for CR.

Objective:To explore the association and gene-environment interaction between single nu-cleotide polymorphisms (SNPs)involved in cell-cell adhesion and non-syndromic cleft lip with or without cleft palate (NSCL/P)among Chinese population.Methods:A total of 806 NSCL/P trios were drawn by an international consortium,which conducted a genome-wide association study (GWAS)using a case-parent trio design to investigate genes affecting risks to NSCL/P.The transmission disequilibrium test (TDT)was used to explore the association between cell-cell adhesion genes,including CDH1,CT-NNB1,PVRL1,PVRL2,PVRL3,ACTN1,VCL,LEF1,and NSCL/P.Conditional Logistic regression models were used to estimate effects on risk of exposed and unexposed children.Four common maternal exposures including maternal smoking,environmental tobacco smoke,alcohol consumption and multivita-min supplementation during pregnancy were included in this study.Results:A total of 226 SNP markers were tested after quality control in this study.Although 23 SNPs in three genes (CTNNB1,CDH1, ACTN1)showed nominal significant association with NSCL/P in the TDT (P <0.05).There were no sig-nificant evidence of linkage and association that remained in the transmission disequilibrium test after Bonferroni correction(P >0.000 2).Tests for gene-environment interaction yielded significant results be-tween rs7431 27 in ACTN1 and environmental tobacco smoke (P =0.000 1 )with an estimated OR (case |G and E)=2.00(95%CI:1 .23 -3.26)and OR (case |G no E)=0.59 (95%CI:0.38 -0.90).Among the lower P value results in gene-environment tests,there were no significant results be-tween rs1 475034,rs370535,rs227341 9 in ACTN1,rs1 06871 in CTNNB1 and environmental tobacco smoke interaction.There were also no significant results between rs7634000,rs2971 366,rs2634553, rs1 489032,rs762481 2 in PVRL3 and multivitamin supplementation during pregnancy in gene-environ-ment tests(P >0.000 2).Conclusion:There is no association between cell-cell adhesion genes,inclu-ding CDH1,CTNNB1,PVRL1,PVRL2,PVRL3,ACTN1,VCL,LEF1,and NSCL/P when the genes are considered alone.But our results suggest that SNPs in ACTN1 may influence the risk to NSCL/P through gene-environment interaction.

Objective To evaluate the safety and efficiency in aortic root disease .Methods From April 2017 to April 2018,46 cases of aortic root disease accepted DavidⅠ[20 cases, 15 males and 5 females, aged(39.6 ±15.8)years, aortic root diameter was(58.3 ±4.4)mm] or Bentall[26 cases, 22 males and 4 females, aged(50.8 ±12.6)years,aortic root diam-eter was(59.5 ±5.0)mm], the data in the peri-operation and heart function in recent period after operation.Results No mortality was observed in the study.Morbidity occurred in both group was comparable.Mean cross-clamp time(129.5 ±28.6) min vs.(94.3 ±35.3)min(P<0.05).Blood transfusion(342.0 ±476.4)ml vs.(330.8 ±651.3)ml(P>0.05).ICU sta-ying time(1.0 ±0.2)day vs.(1.1 ±0.3)day(P>0.05).At the latest visit(10.5 ±6.8)months in David Ⅰ, no obviously regurgitation of aortic valve were observed 0.75 ±0.44 vs 1.0 ±1.3(P>0.05).Conclusion Except for the prolonged cross-clamp time, David Ⅰ is safely and effective in aortic root disease compared with Bentall in peri-operative period .The long term results need further follow-up.

Objective:To investigate the expression and significance of T helper cell 17 (Th17), soluble intercellular adhesion molecule-1 (sICAM-1) and coagulation function in patients with infectious endocarditis(IE).Methods:From December 2016 to December 2018, IE patients in Beijing Anzhen Hospital Affiliated to Capital Medical University who met the inclusion criteria were selected for cardiac surgery to analyze prospectively, 38 IE patients were selected as the observation group, and 30 healthy people were selected as the control group.The concentrations of serum Th17 related factors (IL-1β, IL-6, IL-17 and IL-21), sICAM-1 and coagulation index(P selectin(sP-SLT)) were measured by enzyme-linked immunosorbent assay(ELISA) and the difference between the two groups were statistically analyzed.Results:The concentrations of serum IL-1β, IL-6, IL-17 and IL-21((29.88±6.49), (14.89±3.31), (21.89±3.01), (563.26±67.36) ng/L) in the observation group were significantly higher than those in the control group((16.56±4.11), (7.52±2.34), (12.91±1.01), (423.38±56.49) ng/L)(all P<0.05). The level of serum sICAM-1 and sP-SLT ((1 247.57(581.39, 1 794.66) μg/L, (60.29±6.61) mg/L)in the observation group were significantly higher than those in the control group((837.28(405.68, 954.47) μg/L, (27.37±5.56) mg/L), and the difference was statistically significant( Z=12.37, t=22.30, all P<0.05). The level of serum IL-1β, IL-6, IL-17 and IL-21 in patients with postoperative infective endocarditis((16.19±4.07), (7.73±2.40), (13.83±0.94), (425.33±52.12) ng/L) were significantly lower than those before operation((29.88±6.49), (14.89±2.31), (21.89±3.01), (563.26±67.36) ng/L), and the differences were statistically significant(t values were 11.02, 13.25, 15.76, 9.98, all P<0.05). The levels of sICAM-1 and sP-SLT1 in patients with postoperative infective endocarditis((901.46(472.15, 1276.58) μg/L, (30.70±5.31) mg/L) were significantly lower than those before operation((1 057.26±463.06) μg/L, (60.29±6.61) mg/L)and the differences were statistically significant( Z=11.16, t=21.51, P<0.05). Conclusion:Th17 related factors, sICAM-1 and sP-SLT were highly expressed in IE patients, and the concentrations of these factors decreased after operation, suggesting that the above factors may be used as related factors for the diagnosis and prognosis of IE patients.

Objective: Sex differences have been observed in many aspects of schizophrenia, including cognitive deficits. Despite extensive research into the relationship between metabolic factors and cognitive deficits in schizophrenia, few studies have explored the potential sex difference in their association. Methods: We recruited 358 schizophrenia patients and 231 healthy controls. The participants underwent measurements of body mass index (BMI), waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. Metabolic risk factors included abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. A collection of these metabolic risk factors has been defined as metabolic syndrome. These diagnoses were based on the criteria of the National Cholesterol Education Program’s Adult Treatment Panel III. Cognitive performance was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A descriptive analysis, difference analysis, and linear regression model were used to identify the metabolic risk factors for cognitive function in schizophrenia. Results: Our findings revealed sex differences in the rate of abdominal obesity and hypertension in schizophrenic patients. Additionally, we observed sex differences in the association between metabolic risk factors and cognitive impairment in schizophrenia. Specifically, hyperglycemia was associated with the immediate memory index score of RBANS in male patients, while dyslipidemia was associated with language, attention, delayed memory index scores, and RBANS total score in female patients. Conclusion Our results suggest that sex should be considered when evaluating the impact of metabolic disorders on the cognitive function of schizophrenic patients. Moreover, our study identifies hyperglycemia and dyslipidemia as potential targets for precise treatment by sex stratification, which could benefit the improvement of cognitive impairment in schizophrenic patients.

Objective:To investigate the methylation status of SDC2, PPP2R5C and ADHFE1 genes in stool and their values in the screening of colorectal cancer and precancerous lesions.Methods:From August 2020 to March 2021, 64 patients with colorectal cancer, 72 patients with adenoma, 33 patients with hyperplastic polyps and 59 healthy people were recruited from Qingdao Central Hospital Affiliated to Qingdao University, and the morning stool samples were collected from the research subjects. The genomic DNA was extracted and modified with sulfite. The methylation status of SDC2, PPP2R5C and ADHFE1 genes were detected by methylation specific polymerase chain reaction (MSP), and the fecal occult blood test (FOBT) was performed. Taking the pathological results as the gold standard, receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to compare the effect of combined detection of methylation of three genes and FOBT in predicting colorectal cancer and precancerous lesions. R-Studio software was used to construct a nomogram for the prediction of colorectal cancer with combined detection of gene methylation in stool and other clinical features, and the calibration and validation were performed.Results:The positive rates of combined detection of methylation of SDC2, PPP2R5C and ADHFE1 genes in stool were higher than those of FOBT in colorectal cancer+adenoma [74.3% (101/136) vs. 47.1% (64/136), χ2 = 23.20, P = 0.001], colorectal cancer [90.6% (58/64) vs. 70.3% (45/64), χ2 = 8.91, P = 0.003] and adenoma [59.7% (43/72) vs. 26.4% (19/72), χ2 = 14.43, P = 0.002]. There was no significant difference in the positive rates in hyperplastic polyps [21.2% (7/33) vs. 6.1% (2/33), χ2 = 0.12, P = 0.125] and healthy controls [10.2% (6/59) vs. 8.5% (5/59), χ2 = 4.01, P = 1.000]. The combined detection of gene methylation was better than FOBT in the prediction of colorectal cancer + adenoma [AUC: 0.85 (95% CI 0.80-0.91) vs. 0.71 (95% CI 0.64-0.78), P < 0.05], especially in the prediction of adenoma [AUC: 0.82 (95% CI 0.74-0.89) vs 0.64 (95% CI 0.57-0.69), P < 0.001]. The sensitivity and specificity of ADHFE1 gene methylation status in predicting colorectal cancer were high (90.6% and 96.6%). In colorectal cancer patients over 50 years old, the positive rate of combined detection of gene methylation was higher than that of FOBT [90.2% (55/61) vs. 68.9% (42/61), P < 0.05]. The nomogram calibration curve for predicting colorectal cancer constructed based on the combined detection of gene methylation and each clinical feature showed a high degree of concordance between the predicted and observed diagnostic performance of colorectal cancer. Conclusions:The methylation levels of SDC2, PPP2R5C AND ADHFE1 genes in stool are increased in patients with colorectal cancer or adenoma. The combined detection of gene methylation is expected to be a non-invasive method for the screening of colorectal cancer and precancerous lesions.

Objective To probe into the mechanism of Shexiang Baoxin Pill in homo-therapy for heteropathy for type 2 diabetes mellitus （T2DM） and coronary heart disease （CHD） based on network pharmacology. Methods All chemical components and action targets of these seven traditional Chinese medical in Shexiang Baoxin Pill were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）, Traditional Chinese Medicines Integrated Database （TCMID）, The Encyclopedia of Traditional Chinese Medicine （ETCM） and BATMAN-TCM platform, and the DisGeNET and GeneCards databases were used to obtain CHD and T2DM-related Disease targets. The “drug-component-target” network map was constructed by Cytoscape 3.8.2 software, the protein-protein interaction （PPI） network map was constructed by STRING database, and the GO biological process analysis and KEGG pathway enrichment analysis were performed on the common targets of Shexiang Baoxin Pill for T2DM and CHD using DAVID online database. Results A total of 101 potential active ingredients for the treatment of T2DM and CHD in Shexiang Baoxin Pill were screened out, corresponding to 229 targets. Network analysis results showed that the common main active ingredients in Shexiang Baoxin Pill for treating T2DM and CHD might be chenodeoxycholic acid, ursodeoxycholic acid, cinnamic aldehyde, bile acids, cinnamic acid, and ginsenosides. The results of pathway enrichment analysis showed that the mechanism of action of Shexiang Baoxin Pill in the treatment of type 2 diabetes and coronary heart disease in treating T2DM and CHD might be related to the inhibition of inflammatory response and oxidative stress. Conclusion Shexiang Baoxin Pill could play a role in treating CHD and T2DM through multiple components, multiple targets and multiple pathways, which provided a certain theoretical basis for the clinical application and further research of Shexiang Baoxin Pill.

AIM:To investigate the influence of fat mass and obesity-associated(Fto)gene on the aberrant contraction of aortic smooth muscle in diabetes mellitus(DM)mice,and to explore the mechanism of Fto gene underlying the calcium regulation.METHODS:Smooth muscle-specific Fto gene knockout(FtoSMKO)mice were generated using Cre-loxP technology.The experiment involved 3 groups of mice:wild-type(WT)group,DM model group and FtoSMKO-DM group,with 15 mice in each group.In DM group and FtoSMKO-DM group,type 1 DM was induced by intraperitoneal injec-tion of streptozotocin.The mice in WT group were injected with equal volume of citric acid-sodium citrate buffer solution.The influences of different drugs on the contraction responses of aortic smooth muscle in mice were analyzed using a multi-myograph system.The expression level of FTO protein in the aortic tissues was detected by Western blot.RESULTS:(1)Compared with WT mice,the expression levels of FTO protein in the aortic tissues of DM mice were significantly in-creased(P＜0.01).(2)The expression level of FTO protein in smooth muscle was significantly decreased after knockout of Fto gene(P＜0.01).Compared with WT group,the mice in DM group exhibited a significant decrease in body weight and a marked increase in fasting blood glucose level(P＜0.05).There were no noticeable differences in body weight or fasting blood glucose level between FtoSMKO-DM group and DM group(P＞0.05).(3)The contraction responses of aortic smooth muscle in DM group were substantially increased by phenylephrine compared with WT group.Specifically,vaso-constriction responses mediated by non-L-type calcium channels and store-operated calcium channels(SOCC)were signifi-cantly enhanced in DM group.In addition,the responses mediated by inositol 1,4,5-trisphosphate receptors(IP3R),which facilitate calcium release from the sarcoplasmic reticulum,were significantly enhanced.However,the responses mediated by caffeine-activated ryanodine receptors(RyR),which also facilitate calcium release from the sarcoplasmic re-ticulum,were significantly inhibited(P＜0.05).(4)Compared with DM group,the phenylephrine-induced contraction re-sponses of aortic smooth muscle in FtoSMKO-DM group were greatly weakened(P＜0.05).In particular,the vasoconstriction responses mediated by non-L-type calcium channels and SOCC in FtoSMKO-DM group were greatly suppressed(P＜0.05),while those mediated by caffeine-activated RyR were dramatically boosted(P＜0.05).However,IP3R-mediated responses were not affected(P＞0.05).CONCLUSION:Smooth muscle-specific Fto gene knockout suppresses contractile hyperre-sponsiveness in the aortic smooth muscle of DM mice,which may be attributed to involvement of FTO protein in calcium regulation in the vascular smooth muscle.