Cell-free DNA from bile outperformed plasma as a potential alternative to tissue biopsy in biliary tract cancer.

BACKGROUND: Biliary tract cancers (BTCs) are rare and highly heterogenous malignant neoplasms. Because obtaining BTC tissues is challenging, the purpose of this study was to explore the potential roles of bile as a liquid biopsy medium in patients with BTC. PATIENTS AND METHODS: Sixty-nine consecutive patients with suspected BTC were prospectively enrolled in this study. Capture-based targeted sequencing was performed on tumor tissues, whole blood cells, plasma, and bile samples using a large panel consisting of 520 cancer-related genes. RESULTS: Of the 28 patients enrolled in this cohort, tumor tissues were available in eight patients, and plasma and bile were available in 28 patients. Somatic mutations were detected in 100% (8/8), 71.4% (20/28), and 53.6% (15/28) of samples comprising tumor tissue DNA, bile cell-free DNA (cfDNA), and plasma cfDNA, respectively. Bile cfDNA showed a significantly higher maximum allele frequency than plasma cfDNA (P = 0.0032). There were 56.2% of somatic single-nucleotide variant (SNVs)/insertions and deletions (indels) shared between bile and plasma cfDNA. When considering the genetic profiles of tumor tissues as the gold standard, the by-variant sensitivity and positive predictive value for SNVs/indels in bile cfDNA positive for somatic mutations were both 95.5%. The overall concordance for SNVs/indels in bile was significantly higher than that in plasma (99.1% versus 78.3%, P < 0.0001). Moreover, the sensitivity of CA 19-9 combined with bile cfDNA achieved 96.4% in BTC diagnosis. CONCLUSION: We demonstrated that bile cfDNA was superior to plasma cfDNA in the detection of tumor-related genomic alterations. Bile cfDNA as a minimally invasive liquid biopsy medium might be a supplemental approach to confirm BTC diagnosis.

[Linear correlation between tooth movement and facial profile change in patients with class â ¡ division 1 malocclusion].

Objective: To investigate the correlation between tooth movement and profile change in patients with class Ⅱ division 1 malocclusion. Methods: Pre- and post-treatment lateral cephalograms of 42 patients [10 males and 32 females, (23.8±6.3) years old, mean treatment time: 1.9 years] with class Ⅱ division 1 malocclusion were collected in Department of Oral & Cranio-Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from June 2012 to November 2017. The patients were treated with extraction of four first premolars or two maxillary first premolars. Cephalometric analysis was carried out before and after treatment. Thirty parameters were measured. The changes of soft and hard tissue after orthodontic treatment and their correlations were analyzed using bivariate linear regression. Related factors affecting the upper and lower lip, nasolabial angle (NLA) and mentolabial angle (MLA) were analyzed according to the standardized regression coefficient (Beta). Results: Among all the 30 parameters, 18 parameters were statistically different before and after treatment. After treatment, upper central incisor sagittal distance [(63.87±7.14) mm] and upper lip sagittal distance [(77.73±7.60) mm] were significantly decreased (P<0.05). The changes in 14 parameters after treatment showed linear relationship including strong positive correlation between upper lip sagittal retraction and upper central incisor sagittal retraction (r=0.649, P<0.01). There were moderate positive correlations between upper lip and upper central incisor vertical movement (r=0.544, P<0.01). While the sagittal change of gnathion and the Y-axis angle showed moderate negative correlations (r=0.537, P<0.01). The stepwise multiple linear regression showed that the retraction of upper lip process was correlated with the retraction of upper central incisor, the increase of occlusal plane angle and the increase of upper central incisor angle, which was most correlated with the retraction of upper central incisor (Beta=0.79). The downward displacement of upper lip process was correlated with the downward displacement of upper incisor, the decrease of upper central incisor angle, the decrease of the distance between maxillary first molar and palatal plane, and the increase of occlusal plane angle, which was more correlated with the downward displacement of upper incisor and the increase of occlusal plane angle (Beta=0.59). The downward displacement of lower lip process was correlated with the downward displacement of upper incisor and lower incisor, which was more correlated with the upper incisor (Beta=0.36). Conclusions: The relationship among nose, lips and chin was more coordinated. Incisor retraction had significant influence on lip prominence, and the lower lip position was highly related to the movement of upper incisor in sagittal and vertical dimension after orthodontic treatment in patients with class Ⅱ division 1 malocclusion. However, tooth movement had limited impact on the chin position.

MiR-129-2 weakens proliferation and promotes apoptosis of liver cancer cells by suppressing the Wnt signaling pathway.

OBJECTIVE: To explore the effects of micro ribonucleic acid-129-2 (miR-129-2) on proliferation and migration of liver cancer cells and its possible mechanism. PATIENTS AND METHODS: The expression level of miR-129-2 was measured in liver cancer tissues and adjacent tissues from patients with liver cancer. Its level in liver cancer HepG2 cells and normal liver cells L-02 was also detected via quantitative polymerase chain reaction (qPCR). MiR-192-2 overexpression model was established in the HepG2 cell line. The proliferation and apoptosis levels of cells were determined by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Wound healing assay was performed to detect the migration ability of cells. The expressions level of genes in the Wnt signaling pathway were measured through Western blotting. Xenograft tumor model was conducted in nude mice for exploring the in vivo effects of miR-129-2 on liver cancer growth. RESULTS: The expression level of miR-129-2 was significantly lower in liver cancer tissues than that in adjacent tissues (p<0.01), and it was overtly lower in HepG2 cells than that in L-02 cells (p<0.01). Overexpression of miR-129-2 weakened proliferation and migration abilities of liver cancer cells (p<0.01), and evidently increased apoptosis level (p<0.01). Sex-determining region Y-related HMG-box 4 (Sox4) and matrix metalloproteinase-2 (MMP-2) were downregulated, while phosphorylated glycogen synthase kinase-3ß (p-GSK3ß) was upregulated in liver cancer cells overexpressing miR-129-2. Besides, the weight and volume of tumors in nude mice bearing liver cancer were significantly smaller after overexpression of miR-129-2. CONCLUSIONS: MiR-129-2 weakens proliferation and migration and stimulates apoptosis in liver cancer cells mainly by downregulating Sox4 and inactivating the Wnt signaling pathway.

[Mucosa-associated lymphoid tissue lymphoma in children and adolescents: a clinicopathologic study of 5 cases].

Objective: To investigate the pathological features and clinical manifestations of mucosa-associated lymphoid tissue (MALT) lymphoma in children and adolescents. Methods: Five cases of MALT lymphoma in children were investigated by morphology and immunophenotyping along with clinical follow-up. Results: Five cases of MALT lymphoma occurred in the antrum, orbit, parotid gland and nasopharynx. All patients had no B symptoms and only one patient showed a local mass with ulcer. One case presented with cervical lymph node enlargement, and 4 cases showed no evidence of lymphadenopathy.All cases had pathological features similar to those of adult MALT lymphoma, with proliferation of monocytoid B cells orcentralcyte-like tumor cells, with plasma cell differentiation and lymphoid epithelial lesions.No specific immunophenotypic marker was found. Clonal Ig gene rearrangement was detected in two cases.One patient was treated with rituximab treatment, 1 patient was given anti-Helicobacter pylori therapy, and 2 patients had no additional treatment.The follow-up data showed that 4 patients survived without tumor recurrence. Conclusions: Similar to adult patients, MALT lymphoma in children and adolescents has similar pathological features with indolent clinical course and good prognosis. It is important to note that misdiagnosis and incorrect diagnosis mightoccur because of the young age of the patients.

[Pathologic subtyping of primary lymphoma of breast and prognostic analysis].

Objective: To investigate the pathological types and prognostic factors of primary lymphoma of breast (PLB). Methods: The clinical pathological data of 115 cases of PLB during October 2006 to October 2016 were retrospectively analyzed, and the basic clinical and pathological data, pathology types and the immunohistochemical slides by EliVision two-step method for staining were summarized. Results: Almost all the patients were women (113/115), and the median age was 52 years old (range: 27 to 81 years old). The main symptom was painless progressive mass in breast. Ten cases (8.7%) showed B symptoms. The masses were mainly confined to the unilateral breast (80.9%, 93/115), of which 22 cases showed axillary lymph nodes enlargement in the same side. The average diameter of masses was 3.0 cm (range from 0.5 to 9.0 cm). There is no differences between the sides (left or right). Pathologically, 106 cases (92.2%) were mature non-Hodgkin's B-cell lymphomas, of which there were mainly diffuse large B cell lymphoma (DLBCL, 64.3%) and mucosa associated lymphoid tissue (MALT) extranodal marginal lymphoma (17.4%). Five cases (4.4%) were mature T/NK cell lymphomas, including extranodal nasal NK/T cell lymphoma (1.7%), peripheral T-cell lymphoma non-specific type (0.9%), subcutaneous panniculitis-like T cells lymphoma (0.9%) and undivided (0.9%). Four cases were lymphoblastic lymphoma. According to Ann Arbor staging criteria, 93 cases were stage ⅠE (6 cases were stage ⅠEB), 22 cases were stage ⅡE (4 cases were stage ⅡEB). Ninety-two cases were followed 1 to 122 months (median: 36 months). The five-year overall survival rate was 85.3%, and 13 patients dead. B symptom was one of the factors that affect the prognosis (P<0.05), but the pathological type has no relationship with the prognosis (P>0.05). Conclusions: PLB is relatively rare, the main clinical manifestation is painless mass, which is difficult to distinguish with breast carcinoma. The most common type is DLBCL, followed by MALT lymphoma, while T cell lymphoma is rarely seen. PLB is early stage tumor with good prognosis, while patients with B symptom turn out to suffer worse prognosis.

[High expression of hnRNPAB/Kap1 together promote poor prognosis in HCC].

Objective: To further understand the interaction protein spectrum of heterogeneous ribonucleoprotein AB (hnRNP AB), and to investigate their clinical significance in hepatocellular carcinoma (HCC). Methods: We carried out mass spectrometry to reveal the specific peptides of KRAB-associated protein 1 (Kap1) and hnRNPAB, and verified their interaction by immunocoprecipitation and western blotting. Expression of hnRNPAB/Kap1 proteins were detected by immunohistochemical staining in the tissue microarrays. Categorical data were analyzed by the chi square test or Fisher exact test; enumeration data between groups were compared using Student t-test or Wilcocon signed rank test; the cumulative recurrence and survival rates were evaluated using the Kaplan-Meier method and the differences were assessed using the log-rank test. Results: We identified Kap1 as a molecular partner for hnRNPAB in HCCLM3 cells and HepG2 cells as well. We found that the 5-year survival rate of the Kap1high patients was significantly lower than the survival rate of those of the Kap1low group (36% vs 59% , HR = 1.67, P < 0.001). Similarly, Kap1high HCC patients had the poorest prognosis at 5-years, with higher cumulative recurrence rate than Kap1low patients (72% vs 54%, HR = 1.66, P = 0.001). Univariate and Multivariate analyses revealed that hnRNPAB /Kap1 alone (HR = 1.35 /1.28, P = 0.001) or in combination with Kap1 (HR =1.24 /1.27, P < 0.05) were independent prognostic indicators for overall survival and time to recurrence. Conclusion: In HCC cells, hnRNPAB and Kap1 form protein complexes. The expression levels of hnRNPAB alone or in combination with Kap1 in HCC patients are important because they provide not only a predictor for HCC prognosis but also a therapeutic target for future studies.

A positive crosstalk between CXCR4 and CXCR2 promotes gastric cancer metastasis.

The molecular mechanism underlying gastric cancer (GC) invasion and metastasis is still poorly understood. In this study, we tried to investigate the roles of CXCR4 and CXCR2 signalings in gastric cancer metastasis. A highly invasive gastric cancer cell model was established. Chemokines receptors were profiled to search for the accountable ones. Then the underlying molecular mechanism was investigated using both in vitro and in vivo techniques, and the clinical relevance of CXCR4 and CXCR2 expression was studied in gastric cancer samples. CXCR4 and CXCR2 were highly expressed in a high invasive gastric cancer cell model and in gastric cancer tissues. Overexpression of CXCR4 and CXCR2 was associated with more advanced tumor stage and poorer survival for GC patients. CXCR4 and CXCR2 expression strongly correlated with each other in the way that CXCR2 expression changed accordingly with the activity of CXCR4 signaling and CXCR4 expression also changed in agreement with CXCR2 activity. Further studies demonstrated CXCR4 and CXCR2 can both activated NF-κB and STAT3 signaling, while NF-κBp65 can then transcriptionally activate CXCR4 and STAT3 can activate CXCR2 expression. This crosstalk between CXCR4 and CXCR2 contributed to EMT, migration and invasion of gastric cancer. Finally, Co-inhibition of CXCR4 and CXCR2 is more effective in reducing gastric cancer metastasis. Our results demonstrated that CXCR4 and CXCR2 cross-activate each other to promote the metastasis of gastric cancer.

[Investigation on the application of GBZ/T 229.2-2010--classification of occupational hazards at workplaces Part 2: occupational exposure to chemicals].

Objective: To investigate the application and effectiveness evaluation of the standard of GBZ/T 229.2-2010 in practice, and to explore the applicability, aiming to provide technical evidence for the re-vision of GBZ/T 229.2-2010. Methods: There were 2 questionnaire surveys carried out in the study, including general survey and specific survey. Databases were established and data were input with Excel 2010 and Epi-data version 3.1 software. SPSS version 19.0 software was used for data cleaning and statistical analysis. Results: In total, the general survey received 100 questionnaires, with 59 from occupational health technical ser-vice organizations held by government, and 11 from colleges and universities. The leading three jobs using GBZ/T 229.2-2010 were the occupational hazards evaluation for constructive project (65.0%), lecturing/train-ing (50.0%), occupational hazards monitoring (43.0%), respectively. In the results of feasibility, scores of the fourth part "classification" , the fifth part "the principles of classification management" , annex A "the correct use instructions" were 3.4, 3.3, 3.5 respectively. In total, the specific survey received 27 questionnaires, with 18 from the employers and 9 from occupational health technical service organizations. The awareness rate of GBZ/T 229.2-2010 among occupational health professionals was 72.2%. In the results of feasibility, scores of the level of chemical hazards, occupational exposure ratio, physical labor intensity level, classification of expo-sure to industrial toxicants, principles of classification management, annex A "the correct use instructions" were 3.2, 3.7, 4.3, 4.1, 3.2, 3.2, respectively Conclusions: The results indicates that each part of GBZ/T 229.2-2010 is feasible and practical. But there are still some problems, such as classification of different kinds of chemicals at workplace, and the interaction of occupational exposure to chemicals and other hazards at work-place, etc. We suggest that in the revision of GBZ/T 229.2-2010, the action level of hazards should be clear.

[Clinical data analysis of valvular involvement in Takayasu arteritis].

OBJECTIVE: To investigate the clinical features of valvular lesions in Takayasu's arteritis. METHODS: We analyzed 22 medical records of patients with Takayasu's arteritis and valvular lesions in Anzhen Hospital, Capital Medical University from January 2012 to January 2015. RESULTS: The spectrums of valvular involvements were aortic valve regurgitation (11, 50%), aortic valve stenosis (1, 4.5%), mitral valve regurgitation (1, 4.5%), mitral valve stenosis (1, 4.5%) and multiple valvular diseases (7, 36.5%).64.7% of patients with aortic valve regurgitation had aortic root dilation.Heart failure was the most common manifestation (63.6%). Glucocorticoid and/or immunosuppressant were administrated on 11 (50%) patients.One (4.5%) patient received Tocilizumab injection.Surgeries were performed on 12 (54.5%) patients with cardiac architecture.Reversible changes in cardiac structure were found by echocardiography within one week after surgery (P<0.05). Three patients died during 10-46 month follow-up, with none of whom taking any anti-inflammatory treatments. CONCLUSIONS: Aortic regurgitation is the prominent valvular lesion in Takayasu's arteritis, mostly secondary to aortic root dilation.Operation could block myocardium reconstruction promptly.The early surgical complication is rare, while perivalvular leakage may occur during longstanding follow-up.Poor inflammatory control might lead to poor long-term outcome.

[The effect of paraquat on autophagy in human embryonic neural progenitor cells].

OBJECTIVE: To explore the effect of paraquat (PQ) on autophagy in human embryonic neural progenitor cells. METHODS: Using ReNcell CX cell model. After treatment with various concentration (0.00, 1.00, 10.00 and 100.00 µmol/L) of PQ, CCK8 assay was used to detect the cell viability, the transmission electron microscope was used to observe the the cell ultrastructure, the real-time polymerase chain reaction (RT-PCR) was adopted to detect mRNA expression of autophagy related genes which including LC3, Atg12, Atg5, beclin1, Atg7 and mTOR and apoptosis related genes Bax and Bcl-2. RESULTS: The cell viability was significantly inhibited after administered with 100.00 µmol/L of PQ (P<0.01). The mRNA expression of Beclin1 was significantly up-regulated and the emergency of autophagosome were observed at the concentration of 1.00 µmol/L group, while mild cell apoptosis, significantly up-regulated Atg5, Atg8, Atg7 and Atg12 mRNA expression as well as down-regulated expression of mTOR and Bax were detected at the 10.00 µmol/L of PQ group, howere, the obvious apoptosis and the up-regulated mRNA expression of mTOR and Bax were observed at the 100.00 µmol/L of PQ group, the mRNA expression of Bcl-2 were all down-regulated after administered with 1.00, 10.00 and 100.00 µmol/L of PQ and reached the lowest level at the concentration of 10.00 µmol/L. CONCLUSION: PQ can induced autophagy at the low concentration in ReNcell CX cell and autophagy might serve as a protective mechanism to ameliorate PQ-induced cytotoxic effects but apoptosis will be induced at the 100 µmol/L concentration.

Effect of sevoflurane anaesthesia on hepatic blood flow in infants with obstructive hepatobiliary disease.

BACKGROUND: Currently most studies on anaesthetic effects on hepatic blood flow of cirrhotic patients have been performed on adults or experimental animals. We performed this study to evaluate the effect of sevoflurane anaesthesia on hepatic blood flow in infants with obstructive jaundice by Doppler ultrasound. METHODS: Forty-four infants with biliary atresia (1-3 months of age) scheduled for a Kasai procedure were enrolled. Hepatic blood flow was calculated by Doppler ultrasound measurements before induction, and after inhalation of 2% and 3% sevoflurane. Infants were allocated to three groups according to baseline portal blood flow/hepatic artery blood flow: group A (portal blood flow/hepatic artery blood flow < 1), group B (1 ≤ portal blood flow/hepatic artery blood flow < 2) and group C (portal blood flow/hepatic artery blood flow ≥ 2). Changes in portal blood flow, hepatic artery blood flow and hepatic blood flow were compared among groups. RESULTS: In group A (n = 9), the median (IQR) hepatic blood flow increased after inhalation of 2% sevoflurane compared to that before induction (from 49.7 (32.0-89.0) to 116.1 (40.4-159.1) ml/min; P = 0.035). Whereas in groups B and C in whom the ratio of portal blood flow and hepatic artery blood flow was normal or mildly changed, the increases in hepatic blood flow after sevoflurane anaesthesia were not significant. CONCLUSIONS: For infants with obstructive jaundice that had reduced portal blood flow and compensatory increase in hepatic artery blood flow, sevoflurane may produce a protective effect on hepatic blood flow.

[Identification and significance of myeloid-derived suppressor cells in peripheral blood of breast cancer patients].

OBJECTIVE: To investigate the presence, biological features, and clinical significance of myeloid-derived suppressor cells (MDSCs) in breast cancer patients. METHODS: Eighty-four cases of breast cancer, 37 cases of benign breast tumor and 21 cases of healthy individuals were included in this study. Samples of peripheral blood (2 ml) were collected, and in the breast cancer patients, blood samples were taken both before and after treatment. Flow cytometry using anti-CD11b, CD33, CD14 and HLA-DR antibody was conducted to identify the unique membrane markers of MDSCs, and statistical analysis was performed to explore the relationship between MDSCs and clinical factors. Cell isolation and in vitro assay were used to test T cell function. RESULTS: CD11b(+) CD33(+) CD14(-) MDSCs were present in the blood of breast cancer patients, and these MDSCs were histologically of mononuclear cells. Cell proliferation assay confirmed that MDSCs inhibited proliferation of homologous T cells in vitro. MDSCs levels in patients with breast cancer, benign disease and the health control were (15.93±3.17)%, (8.92±4.42)% and (5.02±2.75)%, respectively, with a statistically significant difference (P<0.001) between breast cancer patients and the other subjects (patients with benign lesions and healthy controls). The expression level of MDSCs in patients with breast cancer was associated with surgical treatment, but not with age, disease stage, lymph node metastasis, ER or PR expression. MDSCs levels were significantly lower in post-operative patients[(7.83±3.78) %] than the (15.37±2.49) % in patients before surgery (P<0.001). CONCLUSIONS: The results of this study demonstrate that MDSCs are present in the peripheral blood of breast cancer patients and the level of MDSCs is associated with surgical treatment. Our findings suggest that CD11b(+) CD33(+) CD14(-) MDSCs are likely involved in breast cancer initiation and development, and may become a novel biomarker to facilitate diagnosis and to predict clinical outcomes of breast cancer.

[Effect of fluorochloridone on oxidative stress in primary co-cultured sertoli-germ cell of rat].

Objective: To explore effect of fluorochloridone on primary co-cultured sertoli-germ cell of rat and its possible mechanism. Methods: primary co-cultured sertoli-germ cell was made by two steps of en-zyme digestion with SD rat testes, after 24h of Sertoli-germ cell isolation, A 0.1% DMSO solvent control group and three FLC exposure groups (10-6、10-7、10-8 mol/L) were selected, cultured cell for 24h, then MTT assay and index detection of oxidative stress were performed. Results: The mortality of primary co-cultured sertoli-germ cell exposed to 10-6 mol/L FLC was significantly higher than control group and FLC exposure groups (10-7、10-8 mol/L) (P<0.05) . 10-6 mol/L FLC reduced enzyme activity of CAT, SOD and GSH. Px, depressed GSH level, el-evated MDA level, and had significant difference than control group and FLC exposure groups(10-7、10-8 mol/L) (P<0.05) . 10-7 mol/L FLC decreased enzyme activity of CAT than control group, depressed enzyme activity of SOD than 10-8 mol/L FLC, lowered GSH level than control group and FLC exposure groups (10-8 mol/L) , and had statistical difference (P<0.05) . Conclusion: FLC can damage primary co-cultured sertoli-germ cell of rat, its possible mechanism is relevant to oxidative stress.

Deletion of the lmna gene induces growth delay and serum biochemical changes in C57BL/6 mice.

The A-type lamin deficient mouse line (Lmna (-/-) ) has become one of the most frequently used models for providing insights into many different aspects of A-type lamin function. To elucidate the function of Lmna in the growth and metabolism of mice, tissue growth and blood biochemistry were monitored in Lmna-deficient mice, heterozygous (Lmna (+/-) ) and wide-type (Lmna (+) (/) (+) ) backcrossed to C57BL/6 background. At 4 weeks after birth, the weight of various organs of the Lmna (-/-), Lmna (+/-) and Lmna (+) (/) (+) mice was measured. A panel of biochemical analyses consisting of 15 serological tests was examined. The results showed that Lmna deficient mice had significantly decreased body weight and increased the ratio of organ to body weight in most of tissues. Compared with Lmna (+) (/) (+) and Lmna (+/-) mice, Lmna (-/-) mice exhibited lower levels of ALP (alkaline phosphatase), Chol (cholesterol), CR (creatinine), GLU (glucose), HDL (high-density lipoprotein cholesterol) and higher levels of ALT (alanine aminotransferase) (p<0.05). Lmna (-/-) mice displayed higher AST (aspartate aminotransferase) values and lower LDL (lowdensity lipoprotein cholesterol), CK-MB (creatine kinase-MB) levels than Lmna (+) (/) (+) mice (p<0.05). There were no significant differences among the three groups of mice with respect to BUN (blood urea nitrogen), CK (creatine kinase), Cyc C (cystatin C), TP (total protein), TG (triacylglycerols) and UA (uric acid) levels (p>0.05). These changes of serological parameters may provide an experimental basis for the elucidation of Lmna gene functions.

Gene polymorphisms associated with susceptibility to coronary artery disease in Han Chinese people.

This study investigated 5 single nucleotide polymorphism (SNP) haplotypes in susceptibility genes for coronary artery disease (CAD) and the putative involvement of these SNPs in CAD in the Chi-nese Han population. From March 2008 to June 2009, we selected 119 CAD patients and 115 subjects not related to the CAD of Chinese Han or-igin as controls. The SNP genotypes were performed by multiplex SNaP-shot technology. The HNRPUL1 gene rs11881940T and GATA2 gene rs3803T loci were highly correlated with CAD (P < 0.05). rs10757278G increased the risk of CAD in patients indicated by an odds ratio (OR) = 1.242 [95% confidence interval (CI) = 1.04-1.49]; rs11881940T and rs3803T were protective factors for CAD with ORs = 0.767 (95%CI = 0.61-0.97) and 0.53 (95%CI = 0.40-0.72), respectively. Analysis of the rs10757278, rs11881940 and rs3803 loci showed that haplotypes ATC (OR = 4.26; 95%CI = 2.85-6.40, P < 0.01), GAC (OR = 1.50; 95%CI = 1.25-1.81, P < 0.01) and GAT (OR = 1.53; 95%CI = 1.12-2.09, P < 0.01) were CAD risk factors, whereas GTC was protective (OR = 0.48; 95%CI = 0.32-0.72, P < 0.01). ATC and glucose were positively correlated (OR = 1.91; 95%CI = 1.01-3.61, P < 0.05). GAT was a risk factor for hyper-tension (OR = 2.86; 95%CI = 1.40-5.83, P < 0.01). In conclusion, poly-morphisms and haplotype analysis of susceptibility genes for CAD can improve predicting this disease and will enable early diagnosis of CAD.

Postoperative morphine concentration in infants with or without biliary atresia and its association with hepatic blood flow.

We measured pre-operative hepatic blood flow and postoperative morphine concentration in infants with or without biliary atresia. Thirty-four infants (0-3 months) with biliary atresia undergoing portoenterostomy (Kasai operation) were included and hepatic blood flow was assessed by magnetic resonance imaging before surgery in 12 of them. Sixteen subjects (0-3 months) without liver disease undergoing abdominal or pelvic surgery acted as controls and six of them had hepatic blood flow assessed. Intravenous morphine (8 µg.kg(-1).h(-1)) was administered to all patients postoperatively. The median (IQR [range]) relative hepatic blood flow was 3.51 (2.72-3.88 [1.68-4.43]) with and 3.15 (2.66-4.42 [2.30-5.01]) without biliary atresia (p = 0.851). The median (IQR [range]) morphine concentration after 24 h infusion was 5.9 (4.5-16.4 [2.9-42.2]) ng.ml(-1) and 6.4 (3.2-12.0 [1.9-48.6]) ng.ml(-1) , respectively (p = 0.460). An inverse regression relation was found between the morphine concentration and the hepatic perfusion index (R(2) = 0.519, p = 0.001). Compensatory increases in hepatic arterial blood flow maintain the total hepatic blood flow in infants with biliary atresia.

Postoperative respiratory and analgesic effects of dexmedetomidine or morphine for adenotonsillectomy in children with obstructive sleep apnoea.

The postoperative respiratory and analgesic effects of dexmedetomidine and morphine have not been compared in children with sleep apnoea having adenotonsillectomy. In a randomised double-blind study we recruited 60 children, aged 2-13 years, who received either intravenous dexmedetomidine 1 µg.kg(-1) or morphine 100 µg.kg(-1) on anaesthetic induction. End-tidal carbon dioxide, Children's Hospital of Eastern Ontario Pain Scale score and supplementary morphine administration were recorded every 15 min for 60 min postoperatively. Over 60 min, mean (SD) end-tidal carbon dioxide was consistently lower with dexmedetomidine compared with morphine (5.4 (0.7) kPa vs 6.0 (0.6) kPa, respectively; p = 0.001). Mean (SD) pain scores were higher with dexmedetomidine (8.1 (2.0) immediately postoperatively and 6.7 (1.0) at 60 min vs 7.6 (1.8) and 6.3 (0.7), respectively, with morphine (p = 0.023)). More patients required supplementary morphine with dexmedetomidine (13/30 (43%) vs 21/30 (70%); p = 0.037). Postoperatively, dexmedetomidine produced less respiratory depression than morphine, but less effective analgesia.