Objective To investigate the effects of antisense Smad2 oligodeoxynudeotides(ODN) on fibronetin(FN) and collagen Ⅳ(ColⅣ) secretion of rat mesangial cells cultured with high glucose, explore the action of Smad2 in the glomerulosclerosis and to find a new method to retard the progress of glomerular fibrosis. Methods 20-mer antisense, sense and random ODNs were designed and synthesized that were phosphorothioate modified to increase stability. The antisense ODN encompassed the ATG of the rat Smad2 gene. ODN was tranferred transiently into rat mesangial cells through liposome. Rat cells were treated with high glucose. mRNA and protein of Smad2 were detected by RT-PCR and cytochemistry. FN and ColⅣ were examined by ELISA. Results Antisense ODN significantly decreased mRNA and protein expression of Smad2 in rat mesangial cells treated with high glucose(P

Objective To investigate the feasibility and effectiveness of internal jugular vein (IJV) intervention therapy in patients with cerebral venous sinus thrombosis (CVST)with color Doppler ultrasound (CDU). Methods Twelve patients with CVST diagnosed by CDU and the 13 IJV lesions (localized luminal stenosis in 9 cases,venous long-segment slender in 2 cases,and right IJV localized luminal stenosis,and long-segment slender on the left in 1 case)confirmed by magnetic resonance venography (MRV)and/ or digital subtraction angiography (DSA)were enrolled retrospectively. CDU examinations were used at 1 week before and after IJV intervention therapy,6 months,1 year,and 2 years. The changes of the maximum diameter and the maximum velocity (V max )of the IJV were compared. The success rate and the long-term efficacy of the intervention therapy were analyzed. Results One week after treatment,the CDU examinations showed that the diameter of IJV stenosis in 13 IJV were increased significantly compared with those before procedure (4. 7 ± 2. 1 mm vs. 2. 3 ± 1. 3 mm;t = 5. 325,P < 0. 01). The velocity of blood flow of IJV was improved compared with before procedure (localized stenosis in 10 IJV[50 ± 15 cm/ s vs. 87 ± 24 cm/ s];t = 6. 285,P < 0. 01). Six of the 12 patients were followed up for a mean of 18 ± 7 months, two patients had restenosis after balloon dilatation. Conclusions For CVST patients with IJV lesions,the preliminary observation has indicated that IJV intervention therapy may improve the lesion lumen and hemodynamics. However,the intervention therapy,especially after balloon dilatation,the incidence of restenosis is higher. CDU can be used as an objective evaluation means for the long-term efficacy of IJV stenosis.

Objective To investigate the effects of trimebutine maleate (TM) on the expression of large conductance calcium-activated potassium channel (BKCa) and ryanodine receptors (RyR)channels at mRNA and protein level in colonic smooth muscle cell of cold restraint stress(CRS)induced rats.Methods A total of 24 Wistar rats were divided into CRS group,CRS with TM group and control group equally.The rats of CRS group were gavaged with 0.9％NaCl (6 ml/kg) daily; the rats of CRS with TM group were gavaged with 15 g/L TM (6 ml/kg) daily and activity was restricted in wire cage at 4 ℃ for two hours,continuously for five days.The rats of control group were gavaged with 0.9 ％ NaCl (6 ml/kg) once without CRS.The amount and characteristics of stool of rats in each group were observed.The colonic smooth muscle was isolated to detect the expression of BKCa and RyR at mRNA and protein level by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot.Results The median of rats defecation particles of CRS group was six,control group was one and CRS with TM group was five.Compared with control group,the defecation appearance of CRS group and CRS with TM group was looser and wetter observed by naked eyes.Compared with control group,there was no obvious pathological changes in CRS and CRS with TM group.There was no significant difference in the mRNA expression of BKCa and RyR channels between control group and CRS group.Compared with control group,the BKCa expression at mRNA level of CRS with TM group increased 1.45 fold.Compared with control group,the RyR2 expression at mRNA level of CRS with TM group increased 1.32 fold.Compared with control group,the BKCa expression at protein level of CRS with TM group increased 1.39 fold,and there was no RyR2 expression band at protein level.Conclusion TM might affect colonic smooth muscle contraction through the upregulation of BKCa expression at mRNA and protein level and RyR expression at mRNA level.

Objective To establish an automatic review plan for coagulation tests with image recognition function,and evaluate the correctness and effectiveness of the plan.Methods Artificial intelligence software and hardware were combined to establish an image recognition system that could automatically determine the characteristics of specimens,blood volume and hematocrit.The correctness of the determination results of specimen character was compared with the visual method,the correctness of the determination results of blood volume was compared with the manual measurement method,and the correctness of hematocrit was compared with the hematology analyzer.According to the flow chart,reference interval,medical decision level,critical value range,relevant literature,work experience and historical data,the autoverification rules of coagulation tests were formulated.The autoverification rules were manually verified,and the autoverification pass rate,true positive rate,true negative rate,false positive rate,and false negative rate were calculated.The change of turnaround time in the laboratory after the implementation of the autoverification scheme was evaluated.Re-sults The accuracy rate of sample trait determination in the image recognition system was 96.72％,and the false negative rate of judging hemolytic,jaundice,and lipoid blood samples as normal samples was 0.04％.The image recognition system was compared with the blood volume data of two groups of specimens measured manually,P=0.4881.The image recognition method was not inferior to the manual measurement method.Comparing the two sets of hematocrit data from the image recognition system and the blood cell analyzer,P=0.1130,the image recognition system was not inferior to the blood cell analyzer.A total of 61 automatic re-view rules for coagulation tests had been established,including numerical abnormalities,logical abnormalities,Delta Check,sample quality abnormalities,reaction curve abnormalities,etc.The automatic review pass rate was 76.19％,true positive rate was 23.77％,true negative rate was 76.19％,false positive rate was 0.04％,and false negative rate was 0.00％.After implementing the automatic audit plan,the turnaround time of sam-ples in each quantile was shortened,with an average shortening time of 13.66 min.Conclusion The applica-tion of image recognition technology in the automatic review of coagulation tests makes the automatic review function more automated and scientific,standardizes specimen quality judgment,improves the accuracy of test results,effectively improves work efficiency and saves manpower.

Objective To evaluate the application value of whole exome sequencing (WES) in diagnosis of NDDs (neuro-developmental disorders) children.Metheod WES was used for the diagnosis of 35 unexplained NDD children, which admitted to the outpatient and ward of Children′s hospital affiliated to Capital institute of pediatric from November 2015 to November 2016.These children′s clinical data was collected detailedly.Using bioinformatics software tools combining with patient′s phenotype, the candidate genetic/genomic variants of these patients were identified from WES data.The final pathogenicity of genetic/genomic variants was interpreted according to the guideline of the American College of Medical Genetics and Genomics (ACMG), meanwhile, the variants validation and co-separation analysis in the parents and their family members were performed by Sanger sequencing, real time-PCR and multiplex ligation-dependent probe amplification (MLPA).Results 14 pathogenic single nucleotide variants (SNVs) and three pathogenic copy number variations (CNVs) were detected in the 35 NDD children, the detection rate in this study is 48.6%.Among the 14 pathogenic SNVs, 11 of them are the definite NDD-related genes according to OMIM database (such as CHARGE syndrome, Wiedemann-Steiner syndrome, Cockayne syndrome, etc.), and six of them are de novo (6/11, 54.6%).Three pathogenic CNVs were identified from WES data, including two microduplications and one microdeletion.Meanwhile, a female child carrying a frame shift mutation in MECP2 was found and the germline mosaicism with low-frequency mutation of this site (8.4%) was confirmed by his father's sperm.Conclusions The diagnosis rate of WES in NDDs children is 48.6% in our small-sample study.In addition to pathogenic/likely pathogenic SNVs, CNVs can be detected successfully from WES data, which effectively improved the diagnosis yield in NDDs children.

Objective To investigate the structure and hemodyanmics characteristics of internal jugular veins (IJV) in normal population . Methods A total of 126 individuals for stroke screening and IJV ultrasound examination from Oct 2017 to May 2018 in our hospital were enrolled .The the level of IJV influx into innominate vein ( J1) ,the level of superior thyroid vein influx into IJV ( J2) and the level of the segment equal to from the bifurcation of common carotid artery to out of skull ( J 3 ) of IJV were evaluated by ultrasound . The parameters included the maximum diameters of the three segments during the smooth respiration period ,cross section area (CSA) ,the maximum velocity (Vmax) ,mean flow volume (FVm) and the maximum pressure gradient ( PGmax) . The parameters of bilateral IJVs were compared . The effects of gender and age on these parameters were analyzed . Results The structures and hemodynamics parameters of left IJV were lower than those of right IJV ( all P < 0 .05) . There was no difference in the parameter left/right ratio between male and female( P >0 .05) . With aging ,the left/right ratio of Vmax and PGmax were decreased ,especially at J1 segment ( P < 0 .05 ) . Conclusions Color Doppler flow imaging can evaluate the IJV structures and hemodynamics by assessing the diameter ,CSA ,Vmax ,FVm and PGmax . Right IJV is the dominated outflow side in normal population . With aging ,the drainage of left IJV is decreased .

Immune checkpoint inhibitors(ICIs)mainly including the CTL antigen 4(CTLA-4)and PD-1/PD-L1,which would offer a notable clinical benefit for non-small cell lung cancer(NSCLC)patients.By strengthening the antitumor immune re-sponse of the body,ICIs lead to immune-related adverse events(irAEs),including checkpoint inhibitor pneumitis(CIP).Although the clinical incidence of CIP is relatively low,some serious cases may prolong or terminate of immunotherapy,even life threateing.This article tries to summarize the clinical manifestations,pathological characteristics,biological mechanism,susceptible population,diagnosis and differential diagnosis,and integrated traditional Chinese and Western medicine treatment of CIP,in order to understand CIP more clearly.

Objective: To compare the diagnostic efficacy of transient elastography (TE) FibroScan and acoustic radiation force impulse imaging (ARFI) combined with serological models including aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis-4 (FIB-4) in hepatitis B virus-related fibrosis. Methods: Sixty-seven patients with chronic HBV infection from October 2014 to May 2017 in Department of Infectious Diseases, Putuo Hospital were enrolled. Both FibroScan and ARFI were conducted in all patients together with serological tests. According to the golden standard of pathology results, the diagnosis values of FibroScan, ARFI combined with APRI or FIB-4 were compared as noninvasive assessment for liver fibrosis. Data with homogeneity of variance were tested by t test, and data with heterogeneity of variance were tested by Mann-Whitney U test. Results: Based on the pathology results, the receiver operating characteristic (ROC) areas under the curve (AUC) of APRI, FIB-4, FibroScan and ARFI in diagnosis of hepatic fibrosis ≥S2 were 0.752, 0.612, 0.885, and 0.850, respectively. The AUC of ROC curve in diagnosis of hepatic fibrosis ≥S3 were 0.746, 0.733, 0.851, and 0.863, respectively. The AUC of ROC curve in diagnosis of hepatic fibrosis ≥S4 were 0.782, 0.705, 0.962 and 0.981, respectively. Combined liver imaging technique and serological tests, such as APRI with FibroScan, APRI with ARFI, FIB-4 with FibroScan or FIB-4 with ARFI, the AUC of ROC curve in the 4 groups in diagnosis of hepatic fibrosis ≥S2 were 0.887, 0.861, 0.893, and 0.853, respectively; in the diagnosis of hepatic fibrosis ≥S3 were 0.873, 0.871, 0.900, and 0.875, respectively; and in diagnosis of hepatic fibrosis ≥S4 were 0.952, 0.981, 0.969, and 0.981, respectively. FibroScan and ARFI were positively correlated with liver inflammation (r=0.467, P=0.000; r=0.371, P=0.002) and jaundice (r=0.424, P=0.000; r=0.0.312, P=0.01), while negatively correlated with platelet (r=-0.331, P=0.006; r=-0.312, P=0.01). The AUC of ROC curve of FibroScan, ARFI and their combination with serological model were significantly increased compared with the single serological model (all P<0.05). Conclusions Serological models such as APRI and FIB-4 as well as liver imaging techniques such as FibroScan and ARFI are all valuable in assessment of hepatic fibrosis, while FibroScan and ARFI have better diagnostic value. ARFI is convenient to application for its integration with the ordinary ultrasound system. The sensitivity and specificity for diagnosis of hepatic fibrosis could be improved by combining serological model with FibroScan or ARFI. Combination of APRI and ARFI show the highest accuracy in diagnosis of hepatic fibrosis. Combination of serological models and transient elastic liver imaging is recommended for assessment and follow-up of HBV-related fibrosis.

Dementia with Lewy bodies(DLB)is the second most common neurodegenerative dementia after Alzheimer's Disease(AD). This article will mainly elaborate the relationship between DLB and blood-brain barrier(BBB)from the following five aspects: (1)The structure and function of BBB; (2)In vivo assessment methods for the blood-brain barrier damage; (3)Evidence for the damage of blood-brain barrier in DLB; (4)The relationship between α-synuclein and the blood-brain barrier; (5)The relationship between APOE and the blood-brain barrier.Future research should focus on the pathogenesis of BBB damage in DLB patients, by which new drug targets for disease diagnosis and treatment may be found.

Objective:Based on UPLC-Q-TOF/MS, to screen a panel of plasma metabolite biomarkers for TB diagnosis and evaluate its diagnostic efficacy.Methods:102 active TB patients [49 males, 53 females, age 40.0(24.0, 48.5) years] from Shanghai Pulmonary Hospital and Shanghai East Hospital from January 2017 to January 2018, 100 TB-IGRA positive patients [55 males, 45 females, age 44.0(37.0, 52.0) years] and 96 healthy controls [55 males, 41 females, age 43.0(32.2, 52.8) years] from Shanghai East Hospital were randomly enrolled. UPLC-Q-TOF/MS technology was used to detect small molecule metabolites in plasma. Combined with multivariate statistical methods VIP and univariate statistic analysis Student's t-test, the main differential metabolites in the plasma of patients with active tuberculosis were filtered. The ROC curve was analyzed for the differential metabolites, and the AUC value, specificity, and sensitivity for diagnosis were used to screen metabolic biomarkers with diagnostic potential. Results:All the samples examined resulted in 10 266 variables, and 1 153 substances were identified by qualitative retrieval through the human metabolome database. After pairwise comparison of samples from the three groups, differential metabolites that simultaneously satisfied VIP > 1 and P<0.05 were plotted into a Venn diagram, and the resulting intersection set contained 38 major differential metabolites. The ROC curve analysis of 38 major metabolites showed that the area under the curve of lactic acid, dopamine, 9-pentadecenoic acid, and 12,13-dihydroxy octadecadienoic acid in the diagnosis of active tuberculosis were 0.92, 0.98, 0.94, and 0.94, respectively, the specificity was both more than 90% and the sensitivity was both more than 80%. The specificity and sensitivity of four metabolites in the combined diagnosis of active tuberculosis were both 94%. Conclusion:Lactic acid, dopamine, 9-pentadecenoic acid, and 12, 13-dihydroxy octadecadienoic acid can be used as potential metabolic biomarkers for tuberculosis diagnosis.