Causal role of gut microbiota in intracranial aneurysm: evidence from a Mendelian randomization study.

OBJECTIVE: An increasing number of studies suggest that the alteration of gut microbiota may affect the pathogenesis of intracranial aneurysm (IA). However, the exact causal relationship between gut microbiota and IA has not been confirmed. MATERIALS AND METHODS: The instrumental variables (IVs) for gut microbiota were obtained from a meta-analysis of a genome-wide association study (GWAS) conducted by the MiBioGen consortium (n = 13,266). The summary of GWAS data for IA was obtained from a large genome-wide meta-analysis involving 23 cohorts. Five Mendelian randomization (MR) methods were used to investigate the causal relationship between gut microbiota and IA (ruptured and unruptured), unruptured intracranial aneurysm only (uIA), and aneurysmal subarachnoid hemorrhage (aSAH) respectively, with inverse variance weighted (IVW) as the main MR method. All MR results were verified through sensitive analyses. RESULTS: Based on the results of the IVW analyses, it was found that five gut microbiota taxa were causally associated with IA (ruptured and unruptured), seven gut microbiota taxa were causally associated with uIA, and six gut microbiota taxa were causally associated with aSAH. Among these taxa, the genus Bilophila was the only one identified to have significant protective effects against IA (ruptured and unruptured), uIA, and aSAH. The sensitivity analysis did not reveal any significant heterogeneity or horizontal pleiotropy among the included IVs. CONCLUSIONS: MR analyses identified several gut microbiota taxa that have a causal relationship with IA. Future research should prioritize understanding the mechanisms underlying this causal relationship, as it is expected to contribute to the development of new methods for predicting and treating IA.

The generation of genuine quadripartite Einstein-Podolsky-Rosen steering in an optical superlattice.

Einstein-Podolsky-Rosen (EPR) steering is a quantum effect based on quantum entanglement and it is the key resource for building quantum networks because of its useful properties. Based on the criterion for genuine multipartite EPR steering, the genuine quadripartite EPR steering is confirmed and it can be generated by a spontaneous parametric down-conversion cascaded process with two sum-frequency generations in an optical superlattice. This occurs either below the oscillation threshold and without oscillation threshold. The influence of the parameters of cascaded nonlinear process on the quadripartite EPR steering among signal, idler, and two sum-frequency beams are also discussed. Choosing appropriate nonlinear parameters can achieve good quadripartite quantum steering. This scheme of the generation of genuine quadripartite EPR steering has potential applications in quantum communication and computing.

[Comparison of 5-year follow-up outcomes between"one-stop"procedure and long-term oral anticoagulants after radiofrequency catheter ablation in patients with atrial fibrillation].

Objective: To compare the 5-year follow-up outcomes of radiofrequency catheter ablation (RFCA) combined with left atrial appendage closure (LAAC) and long-term oral anticoagulant (OAC) after RFCA in patients with atrial fibrillation. Methods: This retrospective cross-sectional study included patients with atrial fibrillation who underwent"one-stop"procedure in the First Affiliated Hospital of Ningbo University from September 2015 to December 2017 (RFCA+LAAC group). Baseline data of patients were collected. Propensity score matching at the ratio of 1∶1 was used to select patients with atrial fibrillation who took long-term OAC after RFCA (RFCA+OAC group). The maintenance rate of sinus rhythm and the incidence of adverse events during follow-up were compared between the two groups. Results: A total of 110 patients were enrolled in the RFCA+LAAC group and RFCA+OAC group, respectively. Age of patients was (67.4±8.8) years in RFCA+LAAC group, and there were 42 (38.2%) female patients. Age of patients was (67.3±7.9) years in RFCA+OAC group, and there were 47 (42.7%) female patients. The patients were followed up for mean of (5.3±1.1) years. There was no significant difference in the maintenance rate of sinus rhythm (log-rank: χ2=0.277, P=0.602) and incidence of ischemic stroke events (2.7% (3/110) vs. 4.5% (5/110), P=0.719) during follow-up between the two groups. The incidence of bleeding events (6.4% (7/110) vs. 18.2% (20/110), P=0.008) and major bleeding events (1.8% (2/110) vs. 8.2% (9/110), P=0.030) was significantly higher in the RFCA+OAC group than in the RFCA+LAAC group. Conclusion: There is no significant difference between RFCA+LAAC group and RFCA+OAC group in maintenance rate of sinus rhythm and incidence of ischemic stroke events. Patients in the RFCA+LAAC group have a lower risk of bleeding events compared to the RFCA+OAC group.

[Feasibility and safety of closing large left atrial appendage using the LAmbre device].

Objective: To evaluate the feasibility and safety of the LAmbre occluder for large-diameter left atrial appendage occlusion. Methods: This study was a retrospective cohort study. Patients with large orifice of the left atrial appendage (≥31 mm) and occlusion with the LAmbre device in the Arrhythmia Center of Ningbo First Hospital were included from June 2018 to March 2020. Baseline data were collected and major perioperative complications of left atrial appendage occlusion (including death, stroke, instrumental embolism, cardiac tamponade, and major bleeding events) were recorded. Patients were followed up 45 days, 6 months and 12 months after surgery. The shunt and device-related thrombosis were recorded by esophageal cardiac ultrasound or pulmonary vein CT, and the occurrence of postoperative thromboembolism, bleeding events, death and other serious adverse events were recorded. Results: The average age and left atrial appendage ostial dimension of 32 patients (37.5% women) included in this research were (70.4±8.4) years old and (34.4±2.9) mm. The LAmbre device was successfully implanted in 31(96.9%) patients. No major complications occurred during the perioperative period. During the 12-month follow-up, pericardial tamponade occurred in 1(3.2%) patient and was recovered after treatment. There was no occluder edge shunt>5 mm in patients followed up by esophageal echocardiography. No significant peri-device leak, device-related thrombus, thromboembolism or death event has occurred. Conclusion: The LAmbre occluder may be feasible and safe for large-diameter left atrial appendage occlusion.

MiR-486 alleviates hypoxia/reoxygenation-induced H9c2 cell injury by regulating forkhead box D3.

OBJECTIVE: Myocardial ischemia-reperfusion injury (IRI) is common in myocardial infarction and is the leading cause of death. Therefore, we investigated the effect of miR-486 on myocardial IRI to explore new targets for clinical treatment of IRI. MATERIALS AND METHODS: We made a rat myocardial IRI model by obstructing the coronary arteries and detected the change of miR-486 expression in rat myocardial tissue. In addition, we induced injury of rat cardiomyocytes (H9c2 cells) by hypoxia/reoxygenation and transfected H9c2 cells with agomir-miR-486 and antagomir-miR-486 to detect the effects of miR-486 on the viability, inflammation and apoptosis of cardiomyocytes. We also used the Targetscan system to predict the direct target of miR-486 and verified the effect of miR-486 on downstream targets through the Dual-Luciferase reporter assay. RESULTS: HE staining and the detection of myocardial injury markers and inflammatory factors verified the effectiveness of IRI rat model. The expression of miR-486 in myocardium of IRI rats was significantly lower than that of the control group. The overexpression of miR-486 in H9c2 cells increased the viability of H9c2 cells and reduced the levels of inflammation and apoptosis. MiR-486 is predicted to have a potential binding site to forkhead box D3 (FOXD3). The Dual-Luciferase reporter assay proved that miR-486 can bind and degrade FOXD3 mRNA. In addition, the overexpression of FOXD3 was found to attenuate the protective effect of miR-486 on H9c2 cells. CONCLUSIONS: MiR-486 protects cardiomyocytes and reduces the levels of inflammation and apoptosis by binding and inhibiting FOXD3 activity. Therefore, miR-486 may become a new target for myocardial IRI therapy.

Hydroxytyrosol suppresses LPS-induced intrahepatic inflammatory responses via inhibition of ERK signaling pathway activation in acute liver injury.

OBJECTIVE: Acute liver injury (ALI) leads to inflammatory response and tissue damage. Inflammatory activation of infiltrative macrophages plays a critical role in liver histology destruction and dysfunction. Hydroxytyrosol (3,4-dihydroxyphenil-ethanol, HT), one of the polyphenols extracted from extra virgin olive oil, currently acts as a treatment for neuroinflammatory responses, but its effect on ALI is elusive. The present study aims to examine the mechanism of HT in macrophages inflammation and evaluate treatment effect of HT on ALI. MATERIALS AND METHODS: In vitro, the expressions of type M1/M2 macrophages biomarkers (CD11c/CD206) and cytokines (TNF-α, IL-1ß, IL-6, IL-10, IL-4) following lipopolysaccharide (LPS) stimulation and HT administration were detected using immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA). Mechanically, HT was used to treat cells and phosphorylation level of extracellular-signal-regulated kinase 1/2 (ERK1/2) protein in cells was analyzed using Western blotting. In murine acute liver injury, inflammatory cytokines and liver injury degree were exhibited by qRT-PCR, IHC and HE staining. Furthermore, hepatic function was exhibited via hepatic metabolic enzymes (ALT/AST) and total bilirubin (TBil) in serum. RESULTS: It was demonstrated that HT treatment attenuated M1 macrophages and increased M2 macrophages after LPS stimulation. Furthermore, the pro-inflammatory cytokine level was descended, while an-inflammatory cytokine was increased via HT suppressing ERK pathway in macrophages. In vivo, HT reduced inflammatory level and mitigated hepatic histological injury, thus ameliorating liver function after acute liver injury. CONCLUSIONS: HT exerts a hepatoprotective and anti-inflammation effect on acute liver injury, which restrains inflammation by inhibiting ERK pathway and regulating macrophages polarization. Moreover, HT prevents liver tissues from inflammatory injury. Therefore, HT serves as a potential implication to treat ALI through modulating inflammation of macrophages.

The role of quinazoline in ameliorating intervertebral disc degeneration by inhibiting oxidative stress and anti-inflammation via NF-κB/MAPKs signaling pathway.

OBJECTIVE: Previous studies have shown that Quinazoline (QNZ) plays extremely important roles in the cellular physiological activity, but it has been rarely examined on cell behavior following intervertebral disc degeneration (IVDD). The aim of this study was to investigate whether QNZ mediates oxidative stress and inflammation contributed to IL-1ß-induced nucleus pulposus (NP) cells degeneration in vitro. PATIENTS AND METHODS: NP were isolated cells from human disc samples collected from patients and the IL-1ß-induced NP cells degenerated model was constructed. The cells were randomly divided into 3 groups, namely, Control group, IL-1ß group (10 µM), QNZ + IL-1ß group (containing 10 nM QNZ and 10 µM IL-1ß). Then, the cell viability was determined by CCK-8 assay, and the levels of collagen I, collagen II, aggrecan, p16, p53, ß-galactosidase (ß-gal), antioxidant enzymes, 8-hydroxy-2-deoxyguanosine (8-OHdG), NF-κB/MAPKs signaling-related proteins and inflammatory factors were examined using Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in NP cells. Finally, the expressions of IL-1ß, IL-6, and TNF-α in the cell supernatants were also determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: This study showed that IL-1ß promoted the progress of IDD, with markedly increased expressions of collagen I, p16, p53, and ß-gal, as well as decreased expressions of collagen II and aggrecan. However, QNZ treatment could reverse the effects of IL-1ß. It was found that cell proliferation was increased, ROS level was decreased, antioxidant enzymes were upregulated, and inflammatory factors were reduced after QNZ stimulation. Moreover, NF-κB/MAPKs signaling proteins IKKß, IκBα, p65, ERK, JNK, and p38 were significantly dephosphorylated by QNZ. CONCLUSIONS: These results indicated that QNZ prevented NP degradation via restraining oxidative stress and inflammation through inhibition of the NF-κB/MAPKs signaling pathway. QNZ may become a novel insight into the therapy of IVDD in the future.

Genuine tripartite Einstein-Podolsky-Rosen steering in the cascaded nonlinear processes of third-harmonic generation.

Recently, Einstein-Podolski-Rosen (EPR) steering has important application in quantum information processing, and it has been received considerable attention because of its uniqueness. The properties of quantum steering among three output fields generated by cascaded nonlinear processes of quasi-phase-matching third-harmonic generation in an optical cavity are investigated. Based on the criteria for multipartite EPR steering which proposed by He and Reid [PRL, 111, 250403 (2013)], the genuine tripartite EPR steering among pump, second-harmonic, and third-harmonic is demonstrated. The parameters which affect the quantum property are also discussed.

Ultrastructure of intestinal mucosa in diarrhea-predominant irritable bowel syndrome.

OBJECTIVES: Impaired intestinal barrier function has been demonstrated in the pathophysiology of diarrhea-predominant irritable bowel syndrome (IBS-D). This study aimed to describe the intestinal ultrastructural findings in the intestinal mucosal layer of IBS-D patients. METHODS: In total, 10 healthy controls and 10 IBS-D patients were analyzed in this study. The mucosa of each patient's rectosigmoid colon was first assessed by confocal laser endomicroscopy (CLE); next, biopsied specimens of these sites were obtained. Intestinal tissues of IBS-D patients and healthy volunteers were examined to observe cellular changes by transmission electron microscopy (TEM). RESULTS: CLE showed no visible epithelial damage or inflammatory changes in the colonic mucosa of IBS-D compared with healthy volunteers. On transmission electron microscopic examination, patients with IBS-D displayed a larger apical intercellular distance with a higher proportion of dilated (>20 nm) intercellular junctional complexes, which was indicative of impaired mucosal integrity. In addition, microvillus exfoliation, extracellular vesicle as well as increased presence of multivesicular bodies were visible in IBS-D patients. Single epithelial cells appeared necrotic, as characterized by cytoplasmic vacuolization, cytoplasmic swelling, and presence of autolysosome. A significant association between bowel habit, frequency of abdominal pain, and enlarged intercellular distance was found. CONCLUSION: This study showed ultrastructural alterations in the architecture of intestinal epithelial cells and intercellular junctional complexes in IBS-D patients, potentially representing a pathophysiological mechanism in IBS-D.

[Predictive value of typical cataplexy+ DQB1*0602 positive to hypocretin-1 reduction in cerebrospinal fluid in patients with narcolepsy].

Objective: To discusses the predictive value of typical cataplexy+ HLA-DQB1*0602 positive to hypocretin-1 (HCRT-1) reduction in cerebrospinal fluid (CSF) in patients with narcolepsy. Methods: A total of 165 narcoleptic patients, who were diagnosed at the Sleep Center of Peking University People's Hospital and Peking University International Hospital from March 2003 to March 2017, were recruited. The CSF HCRT-1 level and DQB1*0602 were measured in all the subjects. The narcoleptic patients were divided into two groups: typical cataplexy+ DQB1*0602 positive were CH group, and others who were not typical cataplexy and DQB1*0602 positive simultaneously were NCH group. The HCRT-1 level in CSF was declared to have a serious reduction when HCRT-1≤110 ng/L. According to this standard, the CH group and NCH group were subdivided into sub-groups and the data was analyzed to investigate the predictive value of typical cataplexy+ HLA-DQB1*0602 positive to HCRT-1 reduction. Results: There were 142 patients in CH group, including 137 patients with HCRT-1 reduction and 5 patients without. There were 23 patients in NCH group, including 15 patients with HCRT-1 reduction and 8 patients without. The positive predictive value of typical cataplexy+ DQB1*0602 positive for the reduction of HCRT-1 in CSF was 96.5%. Typical cataplexy+ DQB1*0602 positive had a good consistency with the HCRT-1 reduction in CSF (χ(2)=26.7, P<0.001). Conclusion: Typical cataplexy+ DQB1*0602 positive has a good predictive value to the HCRT-1 reduction in CSF in patients with narcolepsy.

Brain-derived neurotrophic factor modulates intestinal barrier by inhibiting intestinal epithelial cells apoptosis in mice.

We aimed to investigate the effects of brain-derived neurotrophic factor (BDNF) on apoptosis of intestinal epithelial cells (IECs) and alterations of intestinal barrier integrity using BDNF knock-out mice model. Colonic tissues from BDNF(+/+) mice and BDNF(+/-) mice were prepared for this study. The integrity of colonic mucosa was evaluated by measuring trans-mucosa electrical resistance and tissue conductance in Ussing chamber. The colonic epithelial structure was analyzed by transmission electron microscopy. Apoptosis involvement was determined with TUNEL staining, active caspase-3 immunostaining and Western blotting for the protein expression of active caspase-3, Bax and Bcl-2. The expression levels and distribution of tight junction proteins were evaluated by immunohistochemistry or Western blots. Compared with BDNF(+/+) mice, BDNF(+/-) mice displayed impaired integrity and ultrastructure alterations in their colonic mucosa, which was characterized by diminished microvilli, mitochondrial swelling and epithelial cells apoptosis. Altered intestinal barrier function was linked to excessive apoptosis of IECs demonstrated by the higher proportion of TUNEL-positive apoptotic cells and enhanced caspase activities in BDNF(+/-) mice. Increased expression of Bax and claudin-2 proteins and reduced Bcl-2 and tight junction proteins (occludin, ZO-1 and claudin-1) expression were also detected in the colonic mucosa of BDNF(+/-) mice. BDNF may play a role in the maintenance of intestinal barrier integrity via its anti-apoptotic properties.

[The difference expression and diagnostic value of RPL5 in papillary thyroid carcinoma of children and adults].

Objective: To study the difference expression and diagnostic value of ribosomal protein L5 (RPL5) in papillary thyroid carcinoma (PTC) of children and adults. Methods: Realtime-PCR was performed to detect the expression of RPL5 in 22 PTC tissues and 13 pericarcinous tissues. Receiver operating characteristic (ROC) curve and Youden's index were used to evaluate the diagnostic value of RPL5 in PTC of children and adults. Results: The expression of RPL5 in PTC tissues was higher than in pericarcinous tissues. The area under curve (AUC) was 0.820 (P=0.001), and Youden's index was 0.568. The expression of RPL5 in PTC of adults was higher than children (P<0.05). The AUC and Youden's index were respectively 0.721 (P=0.069) and 0.414 in children, whereas being respectively 0.896 (P=0.0005) and 0.709 in adults. RPL5 in diagnosis of PTC of adults was better than CK19, Galectin-3 and TPO, which are commonly used for the pathologic diagnosis of PTC. Conclusion: The expression of RPL5 in PTC is higher than pericarcinous tissues, and its expression in PTC of adults is higher than children. Furthermore, PTC is a potential indicator for diagnosis of PTC.

Role of transient receptor potential vanilloid 1 in regulating erythropoietin-induced activation of endothelial nitric oxide synthase.

AIMS: Erythropoietin (EPO), the key hormone involved in erythropoiesis, beneficially affects endothelial cells (ECs), but the detailed mechanisms are yet to be completely understood. In this study, we investigated the role of transient receptor potential vanilloid type 1 (TRPV1), a ligand-gated non-selective calcium (Ca2+ ) channel, in EPO-mediated endothelial nitric oxide synthase (eNOS) activation and angiogenesis. METHODS AND RESULTS: In ECs, EPO time dependently increased intracellular levels of calcium; this increase was abrogated by the Ca2+ chelators and pharmacological inhibitors of TRPV1 in bovine aortic ECs (BAECs) and TRPV1-transfected HEK293 cells. In addition, EPO-induced nitrite oxide (NO) production, phosphorylation of eNOS, Akt and AMP-activated protein kinase (AMPK) and the formation of TRPV1-Akt-AMPK-eNOS complex as well as tube formation were diminished by the pharmacological inhibition of TRPV1 in BAECs. Moreover, EPO time dependently induced the phosphorylation of phospholipase C-γ1 (PLC-γ1). Inhibition of PLC-γ1 activity blunted the EPO-induced Ca2+ influx, eNOS phosphorylation, TRPV1-eNOS complex formation and NO production. The phosphorylated level of eNOS increased in the aortas of EPO-treated wild-type (WT) mice or EPO-transgenic (Tg) mice but not in those of EPO-treated TRPV1-deficient (TRPV1-/- ) mice or EPO-Tg/TRPV1-/- mice. Matrigel plug assay showed that EPO-induced angiogenesis was abrogated in TRPV1 antagonist capsazepine-treated WT mice and TRPV1-/- mice. CONCLUSION: These findings indicate the EPO-induced Ca2+ influx via the activation of the PLC-γ1 signalling pathway, which leads to TRPV1 activation and consequently increases the association of the TRPV1-Akt-AMPK-eNOS complex, eNOS activation, NO production and angiogenesis.

BDNF modulates intestinal barrier integrity through regulating the expression of tight junction proteins.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) may play a vital role in the homeostatic regulation of intestinal barrier integrity. We aimed to investigate the physiological role of BDNF in maintaining the intestinal epithelial barrier using postinflammatory irritable bowel syndrome (PI-IBS) mice and explore the underlying molecular mechanisms using intestinal epithelial cells in vitro. METHODS: Postinflammatory-IBS mice were induced by intrarectal administration of trinitrobenzene sulfonic acid and allowed to recover for 28 days. Frequency of defecation, fecal water content, colonic epithelial integrity and expressions of BDNF and tight junction (TJ) proteins (occludin, ZO-1, claudin-1, claudin-2) of the PI-IBS mice were investigated. Based on the results of animal studies, we further performed RT-PCR and Western blots to assess how BDNF stimulation and BDNF knockdown impacted TJ proteins in the ht-29 intestinal epithelial cells. KEY RESULTS: Water content of stools was significantly increased in the PI-IBS mice compared with controls. Colonic mucosa from the PI-IBS mice displayed epithelial barrier defects and exhibited increased protein expressions of BDNF and claudin-2 and decreased protein expressions of occludin, ZO-1 and claudin-1. Furthermore, a siRNA against BDNF in the ht-29 cells could effectively suppress BDNF gene and protein expressions, and subsequently reduce TJ gene and protein levels. When the ht-29 cells were incubated with different doses of exogenous BDNF, significant increases of occludin, ZO-1 and claudin-1 and decreases of claudin-2 protein were observed. CONCLUSIONS & INFERENCES: BDNF may play a role in regulating intestinal epithelial barrier via affecting the expression of TJ proteins.

[The study on the inhibitive effects of recombinant parathyroid hormone (1-34) on osteolysis in a murine calvarial model induced by wear particles].

Objective: To investigate the effect of different doses of recombinant parathyroid hormone (PTH) (1-34) on osteolysis in a murine calvarial model. Methods: In total, 48 adult male C57BL/J6 mice were randomly divided into four groups: the sham group, the vehicle group, the low dose-, and high dose PTH group (n=12 each group). Mice in the PTH groups were treated with local injection of recombinant PTH at 30 or 60 µg·kg-1·d-1, intermittent injection 3 times per week for two weeks. Mice in the sham and vehicle groups received local injection of saline daily. Two weeks after surgery, calvarial tissue and peripheral blood were harvested for further analysis. Osteolysis was assessed by micro-computed tomography. The mRNA and protein expression of osteoprotegerin (OPG) and receptor activator for nuclear factor-κB Ligand (RANKL) of calvarial tissue and peripheral blood were tested by real-time PCR and ELISA, respectively. Results: Compared with the vehicle group, PTH treatment significantly inhibited the severity of osteolysis and improved the bone volume. Real time-PCR and ELISA showed that PTH significantly increased the mRNA and protein expression of OPG and reduced the RANKL/OPG ratio. Conclusion: These findings suggest that local application of PTH could effectively inhibit wear-particle-induced-osteolysis in a murine calvarial model.

Screening for genes that are differentially-expressed between gastric cancer cells and gastric tumor sphere cells using the gene chip technique.

The purpose of this study was to screen for genes that were differentially expressed between a human gastric carcinoma cell line (HGC-27) and their tumor spheres, using the gene chip technique. The HGC-27 cells and tumor sphere cells were cultured in vitro in a sterile environment. Total RNA was extracted from both samples and purified using a standard TRIzol reagent. Total RNA was then hybridized onto a GeneChip, according to the standard protocols provided by the manufacturers of the GeneChip IVT Express Kit. The resulting fluorescence signals were analyzed and displayed using the Cluster and Treeview software programs. Under the criteria for significant differential expression (≥2-fold difference), 610 up- and 1135 down-regulated genes were identified in tumor sphere cells, compared to HCG-27 cells. These genes were involved in cell growth, signal transduction, tumorigenesis, and many other functional aspects of tumor cells. In conclusion, a number of genes were differentially expressed in tumor sphere cells compared to HCG-27 cells. In addition, we identified a close correlation between tumor sphere cells and tumorigenesis.

Linear dependence of the water proton transverse relaxation rate on the shear modulus of hydrogels.

It is found that hydrogelation of peptides enhances the transverse relaxation rate R2 of water protons but has no effect on the longitudinal relaxation rate R1 and the diffusion coefficient D. The magnitude of water proton R2 enhancement increases linearly with the shear modulus G of hydrogels.

Increased cancer risk in patients with haemophilia A: a nationwide population-based 14-year study in Taiwan.

Haemostasis is associated with the development and dissemination of cancer. Whether cancer incidence is increased in haemophiliacs remains uncertain; thus, we aimed to further examine this issue. By using data from the National Health Insurance Research Database in Taiwan, we obtained a cohort of 683 patients with haemophilia A, and compared the incidence rate ratio (IRR) of cancer in this cohort with an age- and sex-matched control of 6830 patients. The log-rank test was used to compare Kaplan-Meier curve of the cumulative cancer incidence between two cohorts. Cox regressions were used to identify independent risk factors of cancer in the study patients. The cancer incidence of patients with haemophilia A was significantly higher compared to the control group (IRR 1.95, 95% CI 1.18-3.09, P = 0.008) during the 14-year follow-up period. The non-lymphoma and non-liver cancer incidence in the haemophilia A cohort remained higher than that of the matched control (P = 0.050 by the log-rank test). The multivariate Cox proportional hazards analysis indicated that age (per year, HR 1.09, 95% CI 1.06-1.12, P < 0.001) was the only significant risk factor for cancer development in haemophilia patients. Patients with haemophilia A had higher cancer incidence than the age- and sex-matched patients, especially for the elderly. With increasing life expectancy for haemophiliacs, physicians should be aware of their cancer development.

Meta-analysis of confocal laser endomicroscopy for the detection of colorectal neoplasia.

AIM: Confocal laser endomicroscopy (CLE) is a recently developed technique used to image colorectal neoplasia. Trials have shown varied results when it is compared with conventional colonoscopy. A meta-analysis was performed to determine the diagnostic accuracy of CLE in the detection of colorectal neoplasia. METHOD: A search was performed for studies assessing the accuracy of CLE in colorectal neoplasia. Studies comparing CLE diagnostic accuracy with conventional endoscopy in the detection of colorectal neoplasia were included. Exclusion criteria included case reports or case series, reviews, duplicate reports or insufficient data in the paper. Seventy-eight titles came up in the initial search and six studies were selected. These were subjected to a meta-analysis. In all, 284 patients with 1030 lesions were included. Each patient underwent conventional colonoscopy and CLE. Per-lesion sensitivity and specificity with 95% CI were calculated. RESULTS: In the individual studies, the sensitivity ranged from 33.3% to 100% and specificity from 71.6% to 99.4%. The weighted and total pooled result (random effects model) for sensitivity was 81% (95% CI 77-85) and for specificity was 88% (95% CI 85-90). The area under the weighted symmetric summary receiver operating curve was 0.9186. In the endoscope-based CLE subgroup, the sensitivity was 82% (95% CI 69-91) and specificity was 94% (95% CI 91-96). In the probe-based CLE subgroup, the sensitivity was 81% (95% CI 76-85) and the specificity was 75% (95% CI 69-81). CONCLUSION: CLE, using either the endoscope-based CLE or probe-based CLE technique, has high sensitivity and specificity. It could therefore be considered as an alternative endoscopic method to distinguish neoplastic from non-neoplastic lesions.