Objective To investigate the expression and clinical significance of Claudin-4 in human se-rous ovarian cancer.Methods 43 cases of serous ovarian cancer from Oct.2008 to May 2014 were studied.Re-al-time quantitative PCR( qRT-PCR) was applied to detect mRNA expression of Claudin-4 in serous ovarian cancer ( n=43 ) in comparison to the corresponding tumor-adjacent tissues.The protein expression of Claudin-4 was measured by immunohistochemistry( IHC) .Results mRNA and protein expression level of Claudin-4 was signif-icantly higher in serous ovarian cancer tissues than in adjacent normal tissues(P<0.05).The high expression of Claudin-4 protein was also associated with large tumor size, lymphatic metastasis, and advanced TNM stage( P<0.05 ) .Conclusions The expression of Claudin-4 is significantly higher in serous ovarian cancer tissues than in the adjacent normal tissues, and it is associated with clinicopathological features.Claudin-4 may become a new marker in early diagnosis and biological target therapy.

Objective To study the dynamic change in plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and its correlation with extravascular lung water index (EVLWI) in patients with septic shock. Methods Sixty-two patients with septic shock admitted to Department of Critical Care Medicine of Beijing Shijitan Hospital were enrolled. The patients were divided into survival group(39 cases)and non-survivors group (23 cases)according to 28-day prognosis. Venous blood was collected after intensive care unit(ICU)admission. The changes in plasma NT-proBNP and hemodynamics indexes levels were analyzed to evaluate their predictive value for clinical outcomes. Results Acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score(23.2±2.5 vs. 28.1±2.6),sequential organ failure assessment(SOFA score:7.74±2.80 vs. 12.43±3.00)and hemodynamics indexes including EVLWI〔ml/kg:7.0(6.0,8.0)vs. 9.0(7.0,12.0)〕,blood lactate(mmol/L):3.60±2.30 vs. 10.40±2.70)and NT-proBNP〔ng/L:945.0(228.0,1 246.0)vs. 5 471.0(3 308.0,11 174.0)〕in survivors were significantly lower than those in non-survivors,and cardiac index〔CI(L?min-1?m-2):4.23±0.85 vs. 3.31±0.74〕, global ejection fraction(GEF:0.205±0.054 vs. 0.149±0.054)were significantly higher than those in non-survivors (P<0.05 or P<0.01). Correlation analysis showed a positive correlation was found between NT-proBNP and EVLWI (r=0.277,P=0.010),and negative correlations were found between NT-proBNP and CI(r=-0.367,P=0.001), GEF(r=-0.259,P=0.017). No correlation was found between NT-proBNP and GEDVI,SVRI. Receiver operating characteristic curve(ROC curve)analysis showed that the area under the ROC curve(AUC)for plasma NT-proBNP predicting the outcome of septic shock patients was 0.869±0.042,95% confidence interval(95%CI)was 0.786-0.952,with the maximum sum of sensitivity and specificity 1.695 to determine NT-proBNP predicting septic shock patient's death cut-off value was 2 071 ng/L,under this cut-off value,the sensitivity was 81.4% and specificity,88.1%. The maximum AUC for EVLWI predicting the outcome of patients with septic shock was 0.690,cut-off value was 7.5 mL/kg,under this cut-off value,the sensitivity was 69.8% and specificity,66.7%. Maximum AUC for CI predicting the outcome of patients with septic shock was 0.785,cut-off value was 3.48 L?min-1?m-2,under this cut-off value,the sensitivity was 69.8%and specificity,66.7%. Maximum AUC for GEF predicting the outcome of septic shock patients was 0.794,cut-off value 0.175,under this cut-off value,the sensitivity was 76.2% and specificity, 81.4%. Multivariate analyses showed CI and NT-proBNP levels were independent predictors of the prognosis〔CI:P=0.001,odds ratio(OR)=9.183,95%CI 2.362-35.694;NT-proBNP:P=0.024,OR=1.000,95%CI 0.999-1.000〕. Conclusion The plasma NT-proBNP level which is correlated significantly to EVLWI can evaluate the severity of septic shock and can predict the prognosis of such patients.

Objective To investigate the value of inflammatory biomarkers such as procalcitonin (PCT),C-reactive protein (CRP),and endotoxin in early diagnosis of bacteriemia patients infected with gram-negative bacteria.Methods A cohort of 79 bacteriemia patients infected with gram-negative bacteria admitted from February 2011 to May 2013 were enrolled for retrospective study.Collected data for analysis included gender,age,disease severity (APACHE Ⅱ score),bacterial isolates from blood culture and other general information.The inflammatory biomarkers such as white blood cell (WBC),neutrophils (NEU),Creactive protein (CRP),procalcitonin (PCT),and endotoxin were assayed within 6 hours after admission.SPSS version 16.0 software was used for statistical analysis.The test of normality was used for analysis of continuous variables,t-test for inter-group comparison and non-parametric statistics for non-normal distribution variables.The AUC of ROC was calculated for determining the sensitivity and specificity of biomarkers for diagnosis of bacteriemia.Results (1) Statistically positive correlations were found among serum PCT,CRP,and endotoxin levels (PCT/CRP =0.916,PCT/endotoxin =0.496,Endotoxin/CRP =0.387),and between those and APACHE Ⅱ score were (PCT/APACHE Ⅱ =0.505,Endotoxin/APACHE Ⅱ =0.467,CRP/APACHE Ⅱ =0.278),respectively,in bacteriemia patients infected with gram-negative bacteria.(2) The receiver operating characteristic (ROC) curve indicated that AUC PCT =0.715 (sen 64.6％,spe 80.7％),AUC CRP =0.666 (sen 67.7％,spe 78.6％),AUC endotoxin =0.771 (sen 78.8％,spe 81.8％) in gram-negative bacteria bloodstream infection patients.(3) The AUC PCT =0.865 (sen 86.2％,spe 77.5％),AUC CRP =0.733 (sen 72.4％,spe 75.0％),AUCendotoxin =0.618 (sen 70.7％,spe 67.5％) in bacteriemia patients infected with gram-negative bacteria in severe sepsis and septic shock group.Conclusions The plasma PCT,CRP,and endotoxin have early predictive value in bacteriemia patients infected with Gram-negative bacteria.In sepsis stage,the level of serum endotoxin has the most significant value for diagnosis.In severe sepsis and septic shock stages,the PCT is the most value for diagnosis of bacteriemia.All biomarkers are positively correlated with severity of the disease.

Objective Design short stature panel with gene curration strategy.Methods The gene curation process was introduced in detail.The strength of a gene-disease relationship was evaluated based on publicly available genetic and experimental evidence.This process in short stature panel design and its effect on gene selection was further demonstrated.Results After gene curation, the number of gene in list was effectively decreased from 1 276 to 705.The panel sequencing reached a diagnosis rate of 19.7% among a cohort of 371 nation-wide ascertained short stature patients.The gene curation process reduced the risk of false positive findings and decreased diagnostic cost and working hours without affecting the diagnosis rate.Conclusion Gene curation is an important step for NGS-based test and should be widely exercised.

OBJECTIVE To investigate the surgical methods for the lesions involved the common carotid artery.METHODS The clinical data of 11 cases with lesions involved the common carotid artery who underwent operations were retrospectively studied.The lesions were 1 case with recurrence tumor after 3/4 partial laryngectomy,1 case with bleeding of the carotid aneurysm caused by tuberculosis,1 case with iatrogenic carotid aneurysm,3 cases with carotid body tumor,1 case with thyroid gland cancer,2 cases with neck tumor,1 case with injury of the carotid artery and 1 case with gas gangrene.RESULTS Common carotid artery was reconstructed in 2 cases after removal of the tumors.The tumors were resected using the carotid shunt in 2 cases.Common carotid artery was sutured in 1 case with neck injury.The common carotid artery was repaired in 1 case with iatrogenic carotid aneurysm after removal of the tumor.The carotid artery was dissected out from the thyroid gland cancer in 1 case.The common carotid artery was reserved in 2 cases after resection of the neck tumors. Neck drainage was performed in the case with gas gangrene.CONCLUSION The surgical methods for lesions involved the carotid artery after removal of the tumors include the reconstruction of the carotid artery, resection and suture the carotid artery,and free of the carotid artery from the tumors.

OBJECTIVE To generate hemophilia A (HA) patient-specific inducible pluripotent stem cells (iPSCs) and induce endothelial differentiation. METHODS Tubular epithelial cells were isolated and cultured from the urine of HA patients. The iPSCs were generated by forced expression of Yamanaka factors (Oct4, Sox2, c-Myc and Klf4) using retroviruses and characterized by cell morphology, pluripotent marker staining and in vivo differentiation through teratoma formation. Induced endothelial differentiation of the iPSCs was achieved with the OP9 cell co-culture method. RESULTS Patient-specific iPSCs were generated from urine cells of the HA patients, which could be identified by cell morphology, pluripotent stem cell surface marker staining and in vivo differentiation of three germ layers. The teratoma experiment has confirmed that such cells could differentiate into endothelial cells expressing the endothelial-specific markers CD144, CD31 and vWF. CONCLUSION HA patient-specific iPSCs could be generated from urine cells and can differentiate into endothelial cells. This has provided a new HA disease modeling approach and may serve as an applicable autologous cell source for gene correction and cell therapy studies for HA.
Cell Differentiation ; Hemophilia A ; pathology ; therapy ; urine ; Humans ; Induced Pluripotent Stem Cells ; cytology ; transplantation ; Urine ; cytology

OBJECTIVETo explore the value of single nucleotide polymorphism array (SNP-array) for the analysis of pediatric patients with growth retardation.

METHODSOne hundred eighty one children with growth retardation were enrolled. DNA was extracted from peripheral samples from the patients, and whole genome copy number variations (CNVs) were detected using Illumina Human Cyto SNP-12. All identified CNVs were further analyzed with reference to databases including ClinGen, ClinVar, DECIPHER, OMIM and DGV as well as comprehensive review of literature from PubMed to determine their pathogenicity.

RESULTSForty seven patients (26%) with abnormal CNVs were detected, which included 12 known microdeletions/microduplications syndrome (26%), 10 pathogenic non-syndromic CNVs (21%), 3 numerical chromosome aberrations (6%), 3 unbalanced translocations (6%), 4 pathogenic mosaicisms (9%) and 15 cases with unknown clinical significance (32%). After excluding obvious numerical and/or structural chromosomal abnormalities, this study has detected 15 pathogenic microdeletions/microduplications sized 5 Mb or less, which may be missed by routine chromosomal karyotyping. In addition, there were 3 cases with loss of heterozygoisty (LOH) containing known or predicted imprinting genes as well as 2 cases with suspected parental consanguinity.

CONCLUSIONSNP-array technology is a powerful tool for the genetic diagnosis of children with growth disorders with advantages of high resolution and improved accuracy.

Adolescent ; Child ; Child, Preschool ; Chromosome Aberrations ; DNA Copy Number Variations ; Developmental Disabilities ; diagnosis ; genetics ; Female ; Humans ; Infant ; Karyotyping ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Polymorphism, Single Nucleotide

Objective To investigate the positive rate of serum biomarkers of 4 infectious diseases including HBV, HCV, HIV, and TP in patients in Jinniu District People’s Hosptial of Chengdu. Methods The results of serum markers of the 4 infectious diseases in 34 080 patients detected in the Laboratory Department of Chengdu Jinniu District People's Hospital were analyzed retrospectively. Results Of these 34 080 patients, the positive rate of HIV antibody (anti-HIV1/2) was 0.32%, the positive rate of hepatitis B surface antigen (HBsAg) was 11.34%, the positive rate of hepatitis C antibody (anti-HCV) was 0.42%, and the positive rate of Treponema pallidum antibody (anti-TP) was 3.08%. The positive rates of anti-HIV1/2, HBsAg and anti-TP in males were higher than those in females (P<0.01). Of the four serum biomarkers detected, Anti-HIV1/2, HB^sAg, and anti-HCV had the highest positive rate in the 30-59 age group, while anti-TP had the highest positive rate in the group older than 60 years old. Conclusion The positive detection rate of serum markers in four infectious diseases in patients in Chengdu Jinniu District People's Hospital before surgery, childbirth and blood transfusion was higher, and the male positive rate was higher than that of the female.

ObjectiveTo systematically review the efficacy and safety of laparoscopic choledochoscopy combined with holmium laser lithotripsy through a meta－analysis. MethodsThis study was conducted based on PRISMA guidelines， with a PROSPERO registration number of CRD42023406221. Chinese databases including CNKI， Wanfang Data， and VIP and foreign language databases such as PubMed， Embase， the Cochrane Library， and Web of Science were searched for original articles on traditional laparotomy versus laparoscopic choledochoscopy combined with holmium laser lithotripsy in the treatment of bile duct stones. Dichotomous variables were assessed by odds ratio （OR） and 95% confidence interval （CI）， while continuous variables were assessed by weighted mean difference （WMD） and 95%CI， and a sensitivity analysis was performed for outcome measures with relatively high heterogeneity. The Begg test and Egger test were used to evaluate publication bias. Stata 15.0 and Review Manager 5.3 were used to perform the statistical analysis. ResultsA total of 26 retrospective studies from China were included in this study， with 2 238 patients in total. The meta－analysis showed that compared with traditional laparotomy for the treatment of bile duct stones， laparoscopic choledochoscopy combined with holmium laser lithotripsy had significantly shorter time of operation （WMD＝－1.26， 95%CI： －1.36 to －1.16， P<0.001）， length of hospital stay （WMD＝－1.93， 95%CI： －2.64 to －1.12， P <0.001）， and time to bowel function recovery （WMD＝－1.52， 95%CI： －1.68 to －1.35， P<0.001）， significantly less intraoperative blood loss （WMD＝－1.79， 95%CI： －1.93 to －1.66， P<0.001）， a significantly lower rate of intraoperative residual stone （OR＝0.15， 95%CI： 0.11－0.20， P<0.001）， and significantly fewer complications （OR＝0.17， 95%CI： 0.13－0.23， P<0.001）. ConclusionCompared with traditional laparotomy， laparoscopic choledochoscopy combined with holmium laser lithotripsy shows better efficacy in the treatment of bile duct stones.