Objective:To investigate the effects of Leflunomide and Azathioprine on serum chemokine cx3cl1(fractalkine), cathepsin S and vascular cell adhesion molecule-1(VCAM-1)in elderly patients with lupus nephritis.Methods:Sixty elderly patients with lupus nephritis admitted to our hospital from January 2017 to July 2019 were selected as the research objects.Patients were divided into two groups by using a random number table method: the Leflunomide group(treated with Leflunomide plus conventional treatment)and the Azathioprine group(treated with azathioprine plus conventional treatment)(n=30, each group). Serum levels of fractalkine and cathepsin S and urine VCAM-1 level before and 6, 9 and 12 months after treatment were measured in the two groups and statistically analyzed.Results:In both groups, serum fractalkine levels were decreased after versus before treatment( F=123.029 and 99.041 respectively, P=0.000). At 6 months after treatment, serum fractalkine level was lower in the leflunomide group(2.34±0.95)μg/L than in the Azathioprine group(2.97±1.01)μg/L( t=2.489, P=0.016). Serum cathepsin S levels were decreased in both groups after treatment( F=106.733 and 64.928, P=0.000). Serum cathepsin S levels were lower in the Leflunomide group that in the azathioprine group at 6 and 9 months after treatment[(24.31±3.15)μg/L vs.(26.92±4.02)μg/L, (21.72±2.67)μg/L vs.(23.89±2.75)μg/L, t=2.799 and 3.101, P=0.007 and 0.003]. After treatment, urinary VCAM-1 levels were decreased in both two treatment groups( F=907.450 and 858.114, P=0.000). At 6 months after treatment, urine VCAM-1 level was lower in the Leflunomide group than in the Azathioprine group[(74.36±9.17)μg/L Cr vs.(86.91±9.22)μg/L Cr, t=5.286, P=0.000)]. The incidences of adverse reactions were low in the two groups, and the difference was not statistically significant. Conclusions:Leflunomide and Azathioprine can effectively reduce serum levels of fractalkine and cathepsin S and urinary VCAM-1 in elderly patients with lupus nephritis, which suggests that Leflunomide and Azathioprine have similar effects in inhibiting inflammatory reaction, cell matrix degradation and remodeling and vascular cell adhesion.But at early stage of therapy, the effect of Leflunomide was better than that of Azathioprine.And two drugs can be selected according to the specific clinical situation.

Objective To study the influence of Nictinamide on the endotheline(ET-1)in patienta with pulmonary arterial hypertension(PAH).Methods 66 cases of PAH were divided randomly into two groups (n=33for each):the Nictinamide treatment group and the control group.The changes of endotheline were compared before and after treatment.Results After treatment serum endotheline was significantly lower in the treatment group(P＜0.01),but there was no difference in the control group before and aftertreatment(P＞0.05).The significant difference was observed between treatment group and control group(P＜0.01).Conclusion Nictinamide will reduce the level of endothellne and confers some degree therapeutic and preventive value for PAH.

Objective:To investigate a classification on age of diagnosis and its clinical characteristics in hospitalized elderly patients with first diagnosed Crohn's disease.Methods:This was retrospective case-control study.A total of 181 newly diagnosed CD patients were admitted to Huadong Hospital from January 2005 to December 2019.According to Montreal CD classification criteria based on the age at the time of diagnosis(sub-grouping A3 into A3 and A4 in this paper), 181 CD patients were classified into four groups: the A1 group(≤16 years, n=4), A2 group(17-40 years, n=60)and A3 group(41-59 years, n=63)(above three as control groups), and the A4 group[≥60 years, with elder-onset Crhon's disease(EOCD), n=54]as a study group.Results:A total of 181 first diagnosed CD patients who met the diagnostic criteria were included in this study.During the investigation period, the total incidence rate of CD was 37.90/100, 000, and the total prevalence rate of CD was 142.79/100, 000.Among the 181 first diagnosed CD patients, there were 4 patients(2.2%)with age of diagnosis of ≤16 years(group A1), 60 patients(33.2%)with age of diagnosis of 16-40 years(A2), 63 patients(34.8%)with age of diagnosis of 41-59 years(A3)and 54 patients(29.8%)with age of diagnosis of ≥=60 years(A4). Of these first diagnosed CD patients, male were dominant in A2 group(51 males / 9 females), while the ratio of males and females tended to be the same(32 males /31 females)in A3 group, and the proportion of female patients was greater than that of male patients in A4 group(25 males /29 females)( P<0.0001). The main CD lesion was ileocolic type in the EOCD group, accounting for 57.4%( P=0.0077). The incidence rate of ileus type CD was 42.6%( P=0.1942). Among the 163 CD patients who underwent colonoscopy, under Simple Endoscopic Score for CD(SES-CD)evaluation, the proportion of SES-CD severity type in EOCD group was as high as 82.2%, which was higher than that in the A3 group(51.7%, P=0.0187). All CD patients underwent pathological examination.There were 173 cases(95.6%)with focal lymphocytic infiltration, 120 cases(66.3%)with inflammatory infiltration on the crypt epithelial and 82 cases(45.3%)with non-caseous granuloma tissue.In the EOCD group, non-caseous granuloma accounted for 61.1%, which was higher than that in the A3 and A2 groups( P=0.0318). In the EOCD group, the non-complication rate was 1.89%, and the incidence rates of 3, 4 and ≥5 complications were 14.8%, 22.2% and 24.1%, respectively( P<0.0001, P=0.0280, 0.0141 and 0.0013). The sulphasalazine(SASP)alone was the main treatment method, accounting for 42.6%( P=0.0038), and the surgery accounted for 24.1%( P=0.9598). Conclusions:The incidence and trend of EOCD are basically consistent with those of adult-onset CD and showed an rising volatility.Incidence rate of EOCD is higher in females than in males.EOCD lesions of visual observation under endoscope are serious.The detection rate of non-caseous granulomas and related scars is high under microscope.EOCD patients have many complications, and SASP alone is the main treatment method.

Objective:To investigate the relationship between genotype and phenotype in children with CRB1 mutated Leber congenital amaurosis (LCA) and early onset retinal dystrophy (EOSRD). Methods:A retrospective clinical study. From January 2013 to December 2019, 10 children with CRB1 mutated LCA/EOSRD were enrolled in the study. The patients were identified as CRB1 mutation by the second generation targeted capture sequencing, Sanger sequencing and the family segregation analysis. All children underwent electroretinogram (ERG) and fundus examination. At the same time, 6 cases were examined by optical coherence tomography (OCT); 1 case was examined by fluorescein fundus angiography (FFA), 7 cases were examined by wide-angle laser scanning ophthalmoscope (UWF SLO). Results:There were 6 cases of LCA and 4 cases of EOSRD in 10 patients with CRB1 gene mutations. The average age of first visit was 3.61 years old. The light and dark wave of ERG was flat in 6 cases, and decreased in 4 cases. A total of 19 pathogenic mutations were detected. There were 1 homozygous mutation and 9 compound heterozygous mutations. There were 4, 2 and 1 cases of "copper-coin" like, "salt and pepper" like and "osteocyte" like pigment changes in retina, 1 case of "crystalline pigment" change and 2 cases of macular pigment scar. In 7 cases of UWF SLO examination, different degrees of para-arteriolar pigment epithelium retention (PPRPE) were found in the middle and peripheral fundus. In 6 cases examined by OCT, the outer layer of retina atrophied and the band of ellipsoid disappeared. Symmetrical cystoid macular edema, splitting cystoid macular degeneration and adhesion of epi-macular membrane to optic disc and macular area were found in 1 case, respectively, the retinal structure was rough and thickened, and the fovea became thinner in 3 cases. In FFA examination, 1 case showed uveitis-like changes with late optic disc fluorescein staining, macular fluorescence accumulation, strong fluorescence diffusing along the blood vessels in each quadrant, peripheral PPRPE of "frost-branch" like strong fluorescence. Conclusion:The relationship between genotype and phenotype of CRB1 mutation is complex, and PPRPE is a common characteristic change.

Objective To investigate the mechanism underlying the WNK4 kinasemediated inhibitory effect on BK channel. Methods Cos-7 cells were cotransfected with BK in combination with either CD4 (control group) or wild type WNK4 (WNK4-WT).Immunostaining and confocal microscopy,chemiluminescence,Western blotting analysis were then employed to determine the BK localization in cells,BK surface expression and total protein level,respectively.To further investigate whether the reduction of BK protein expression is due to an increase in degradation through a lysosomal pathway,BK protein level was determined after treated with bafilomycin A1(Baf A1),a proton pump inhibitor affecting lysosomal degradation. Results Immunostaining and confocal microscopic study showed that BK was localized both in plasma membrane and cytosol in the control group.After cells transfected with WNK4-WT,BK expression was markedly reduced.Chemiluminescent assay found that BK surface expression level was 299.9±18.6 in the control group,whereas it was significantly reduced (148.4±13.7,P＜0.01) in the WNK4-WT group.Western blotting analysis showed that total BK protein level was markedly reduced in the presence of WNK4-WT compared to the control group.WNK4-WT was shown to significantly reduce the BK total protein level (42.3％±15.2％) compared to the control group (100％) (P＜0.01).When the cells was treated with Bafilomycin A1 (Baf A1,0.5 μmol/L),WNK4-mediated reduction in BK protein was reversed (82.2％±12.1％,P＜0.05). Conclusions WNK4 inhibits total and surface protein expression of BK in Cos-7 cells whick is likely due to an increase in BK degradation through a lysosomal pathway.

Objective To investigate the low polarity compounds from Polygonum paleaceum Wall .Methods The ethyl alcohol extracts of Polygonum paleaceum Wall were extracted with petroleum ether .The components were separated and iden-tified by GC-MS and elucidated by the comparison with the standard mass spectral data .The relative contents in percentage were calculated using the area normalization method .Results 40 compounds were identified .Naphthalene and (E)-9-octadece-noic acid ethyl ester were the main components .Conclusion The low polarity components of Polygonum paleaceum Wall were mainly consisted of naphthalene and (E)-9-octadecenoic acid ethyl ester (27 .02% ) ,along with hexadecanoic acid (4 .18% ) , 13 ,27-cycloursan-3-one (2 .55% ) and cis-11-eicosenoic acid (1 .31% ) .

Objective To improve detection rate and diagnostic accuracy of single ventricle(SV) in obstetric fetal echocardiography,to investigate the common types and complicated malformations of SV in the fetus,and to summarize the differential announcements in diagnosing fetal SV.Methods In 345 fetal hearts which were diagnosed as congenital heart disease by fetal echocardiography in our hospital,73 cases diagnosed as SV,including 3 cases appeared as ones of twins,were included in this study.Systemic scanning and multiple-views fetal echocardiography were used to examine these enrolled fetuses.Results In all 73 SV eases,3 cases were diagnosed as simple SV,the others were diagnosed as SV accompanied with other abnormalities,among them 44 cases accompanied with single atrium,18 cases with single atrium and persistent truncus arteriosus,2 cases with pulmonary atresia,20 cases with pulmonary artery stenosis,4 cases with partial atrioventricular septal defect,3 eases with aorta dysplasia or aortic valve dysplasia.SV types were classified as 24.7％ in type A,13.7％ in type B,46.6％ in type C and 15.0％ in type D respectively.68.2％ of the cases were diagnosed with aortic D-transposition,and 45.2 ％ with common inlet,42.5 ％ with single inlet and 12.3 ％ with double inlet respectively.42 SV cases were executed termination of pregnancy which 11 cases were confirmed by pathology and the other 31 cases were out of following-up.Conclusions Most cases of fetal SV were accompanied other abnormalities and simple SV was rare.Type C in which ventricular structure was combined with left and right ventricle was the most common type.To avoid the false diagnosis,much attention must be paid to distinguish big papillary muscle and abnormal muscle bundle from interventricular septum during ultrasonic examination.

Objective To investigate the common types of fetal cardiac malformations and complicated malformations,and to assess the value of classifying on these types.Methods 3201 pregnant women were undergone with fetal echocardiography (FECG),239 fetuses of them were diagnosed to be suffered with congenital heart disease(CHD),and 8 cases were one of twins with abnormal heart confirmed by FECG.All new-births were examined by echocardiography within half year after their births.Results 155 complex CHD in 239 fetuses were diagnosed by FECG,in them the common malformations were in turn 59 cases with diagnosed univentricular heart,29 cases with double outlet right ventricle,19 with atrio ventricular septum defect,12 with tetralogy of Fallot or quinalogy of Fallot,11 with persistent truncus arteriosus,6 with right ventricular dysplasia syndrome,6 cases transposition of the great vessels.100 cases were induced labor,41 of them were comfirmed by pathology.16 fetuses were born,123 cases were being pregnanted or un-followed up.Conclusions Complex and multi-malformation were common in fetal cardiocascular abnormalities.Diagnosing rate of fetal CHD(FCHD) in our enroll fetuses was 7.47 ％,rate of complex CHD vs CHD was 64.85 ％.According different types of FCHD,able to be operated or not after birth,surgery methods,as well as prognosis evaluations,all FCHD cases were classified into three subtypes:curable type,curable palliative type and untreatable type.This newly viewpoint will help pregnant women and their family to make reasonable selection.

Objective To investigatethe role of NF-κB played in the process of the cord blood monocytes differentiating into dendritic cells(DCs)induced by astragalus polysaccharide(APS)and to explore the signal transduction pathway involved in this process.Methods Umbilica]cord blood was collected in aseptic conditions.The cord blood monocytes were obtained by density gradient centrifugation and were divided into three groups afterwards.In the control group.cells were cultivated in the RPMI 1640 complete medium.In the APS group.cells were cultivated in the RPMI 1640 complete medium containing 100 mg/L APS.In the PDTC group:cells were treated with 10 μmol/L disulfide carbamate(PDTC).NF-κB inhibitor in 30 min followed by cultivalion in the RPMI 1640 complete medium containing 100 mg/L APS.,The morphological changes were observed during the process of cultivation by the optical microscope and transmission electron microscopy.Cells were collected 12 d later and the cellular immunophenotyping was assayed by FCM.,The activation and migration of NF-κB fluorescence in the cells was examined by the immunoflouresce microscopy.Results (1)Cells in the control group grown up without cluster forformation and were found fusiform and macrophage-like in 12 d.Cells in the APS group grown up in clnstem,and morphological changes were found from the circular shape to a typical dendritic cells-like shape.Cells in the inhibitor group grown up slowly and without cluster formation,and cell morphdogy had no significant change.(2)The expression of DCs-specific antigen CD80,CD83 and CD86 in the APS group was higher than that in the control group and inhibitom group(P<0.01).The expression of those antigen in the control group and PDTC group was similar and had no statistically significance(P>0.05).(3)NF-κB fluorescence in the nuclei was examined by the immunoflourescence microscopy and was much higher in the APS group than that in khe other groups,especially in 72 h with the activation rate of NF-κB (75.20±7.37)%,while(13.20±3.46)% of PDTC group and(8.20 ±1.92)%,respectively(P<0.01).Conclusion Astragalus polysaccharide can induce the differentiation of umbilical cord blood cells into DCs,and NF-κB is the key component of the signal transduction pathway involved in this process.

Background: Dysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients. Methods: A total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics. Results: Compared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower.Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP.The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer. Conclusion Diabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.