Evaluation of miR-429 as a novel serum biomarker for pancreatic ductal adenocarcinoma and analysis its tumor suppressor function and target genes.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer. Various microRNAs have been identified to play an important role in PDAC. The study aimed to explore the role of miR-429 in PDAC. PATIENTS AND METHODS: The expression and prognostic value of miR-429 were first analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Next, miR-429 expression was evaluated in the tissues and serum of 90 patients with PDAC. CCK8, SRB, wound healing and transwell assays were used to determine the effect of miR-429 on the proliferation, invasion, and migration of PDAC cells, respectively. Weighted gene co-expression network analysis (WGCNA), correlation analysis, TargetScan, and miRDB databases were used to screen and identify the target genes of miR-429. RESULTS: The results revealed that the expression of miR-429 was downregulated in PDAC tissues and the serum compared with those in normal tissues and the serum of healthy volunteers, respectively. The decreased expression of miR-429 was significantly associated with shorter overall survival. The overexpression of miR-429 significantly inhibited the proliferation, invasion, and migration of PDAC cells. Potential target genes of miR-429 were identified using WGCNA and bioinformatics analysis, and the results showed that cadherin 11 (CDH11), inositol polyphosphate-4-phosphatase type I (INPP4A), laminin gamma 1 (LAMC1), low density lipoprotein receptor-related protein 1 (LRP1), and quaking (QKI) were potential target genes of miR-429 in PDAC. Lower expression of CDH11 and QKI was associated with a more favorable prognosis in patients with PDAC. The overexpression of miR-429 could inhibit the expression of CDH11 and QKI. A nomogram model, involving miR-429, CDH11, and QKI, was subsequently constructed to determine their ability to accurately predict overall and disease-free survival in patients with PDAC. CONCLUSIONS: Taken together, miR-429 is involved in the development and progress of PDAC. MiR-429 could be recommended as a prognostic biomarker and therapeutic indicator in PDAC diagnosis.

Cardiac autonomic function and insulin resistance for the development of hypertension: a six-year epidemiological follow-up study.

BACKGROUND AND AIMS: To explore the impact of cardiac autonomic function (CAF) and insulin resistance (IR) on incident hypertension. METHODS AND RESULTS: In 1996, 1638 subjects finished baseline examination, which included anthropometry, blood pressures, CAF, blood biochemistry, plasma insulin, urine examination and electrocardiogram. CAF included standard deviation of normal-to-normal intervals or RR intervals (SDNN), low- and high-frequency power spectrum (LF and HF), and LF/HF ratio at supine for 5 min, the RR interval changes during lying-to-standing maneuver, and the ratio between the longest RR interval during expiration and the shortest RR interval during inspiration (E/I ratio). We used homeostasis model assessment to define beta cell function (HOMA-B) and insulin resistance (HOMA-IR). In total, 992 non-hypertensive participants completed the follow-up assessment in 2003 and 959 participants were included for the final analysis. Incident hypertension was determined by blood pressure status at follow-up. In unadjusted model, both square root of HOMA-IR (OR:3.37, 95%CI: 2.10-6.64) and HOMA-B (OR:0.996, 95%CI: 0.992-0.999) were related to incident hypertension. In multivariate model, square root of HOMA-IR (OR:1.97, 95%CI: 1.05-3.70), but not HOMA-B, was associated with incident hypertension. After further adjustment for baseline CAF, the positive relationship between the square root of HOMA-IR and incident hypertension disappeared. In contrast, LF/HF ratio (OR:1.18, 95%CI: 1.01-1.37), HF power (OR:0.98, 95%CI: 0.96-0.999), and E/I ratio (OR:0.71, 95%CI: 0.54-0.95) were each independently associated with incident hypertension after further adjustment for HOMA measures. CONCLUSION: Sympathovagal imbalance with an apparently decreased parasympathetic tone is an important predictor of incident hypertension independent of IR.

Defect modeling in spreading nematic droplets.

Experiments by Poulard and Cazabat [Langmuir 21, 6270 (2005)] on spreading droplets of nematic liquid crystal (NLC) reveal a surprisingly rich variety of behavior, including at least two different emerging length scales resulting from a contact line instability. In earlier work [Cummings, Lin, and Kondic, Phys. Fluids 23, 043102 (2011)] we modified a lubrication model for NLCs due to Ben Amar and Cummings [Phys. Fluids 13, 1160 (2001)] and showed that, in a qualitative sense, it can account for two-dimensional (2D) versions of the observed behavior. In the present work we propose a different approach that allows us to explore the effect of anchoring variations on the substrate, again in a 2D geometry. This in turn gives a simple way to model the presence of defects, which are nearly always present in such flows. The present model leads to additional terms in the governing equation. We explore the influence of these additional terms for some simple flow scenarios to gain insight into their influence.

Using ileocolic artery for successful graft salvage in a recipient with hepatic artery thrombosis after living donor liver transplantation: case report.

Hepatic artery (HA) occlusion is a sinister complication after liver transplantation. It frequently leads to graft loss if untreated. Urgent arterial reconstruction with thrombectomy may reduce the need for retransplantation. Living donor liver transplantation (LDLT) offers further challenges due to smaller-caliber vessels, shorter vascular stumps, and occasional multiple HA. Alternatives to the HA are needed when the native HA cannot be used or when HA complications develop. We describe the use of the recipient's ileocolic artery as an alternate HA in adult LDLT. Graft revascularization and timely salvage resulted in good patient recovery. A 6-month computed tomography angiography follow-up showed patency of the alternate vessels reconstructed.

Seasonal variation and health risk assessment of polycyclic aromatic hydrocarbons in Miaoli city, Taiwan.

The ambient PAHs levels in the downtown area of a traditional small city were analyzed for winter and summer seasons. A total of 16 PAHs in gaseous and particulate phase were quantified. The average gaseous PAHs were 2,189 ± 1,194 and 623.8 ± 545.1 ng/m(3) in winter and summer seasons, respectively. For the PAHs in particulate phase, they were 40.32 ± 12.15 and 11.99 ± 5.63 ng/m(3) in winter and summer seasons, respectively. These values were comparable to those reported for large cities or even higher. The estimated BaPeq was 12.32 ± 6.34 ng/m(3). As low-molecular-weight PAHs primarily existed in gaseous phase, high-molecular-weight PAHs in particulate phase became a significant fraction of total particulate phase PAHs. Particulate phase PAHs was significantly inversely associated with the ambient temperature for each individual PAHs species. However, this relationship did not exist for high-molecular-weight PAHs in gaseous phase. The results indicated the photo-degradation of high-molecular-weight PAHs should warrant a further thoughtfully investigation.

Characteristics of polycyclic aromatic hydrocarbon emissions of particles of various sizes from smoldering incense.

Release of polycyclic aromatic hydrocarbons (PAHs) in particles of various sizes from smoldering incenses was determined. Among the three types of incense investigated, yielding the total PAH emission rate and factor ranges for PM0.25 were 2,139.7-6,595.6 ng/h and 1,762.2-8,094.9 ng/g, respectively. The PM0.25/PM2.5 ratio of total PAH emission factors and rates from smoldering three incenses was greater than 0.92. This study shows that total particle PAH emission rates and factors were mainly <0.25 µm. Furthermore, the total toxic equivalency emission rates and factors of PAHs for PM0.25 were 241.3-469.7 and 198.8-576.2 ng/g from the three smoldering incenses. The benzo[a]pyrene accounted for 65.2%-68.0% of the total toxic equivalency emission factor of PM2.5 for the three incenses. Experimental results clearly indicate that the PAH emission rates and factors were influenced significantly by incense composition, including carbon and hydrogen content. The study concludes that smoldering incense with low atomic hydrogen/carbon ratios minimized the production of total polycyclic aromatic hydrocarbons of both PM2.5 and PM0.25.

A retrospective study of catastrophic invasive fungal infections in patients with systemic lupus erythematosus from southern Taiwan.

As very few large scale publications of invasive fungal infection (IFI) have been reported in lupus patients from individual medical centers, a retrospective study was performed from 1988 to 2009 in southern Taiwan. Demographic characteristics, clinical and laboratory data, and mycological examinations were analyzed. Twenty cases with IFI were identified in 2397 patients (0.83% incidence). There were 19 females and one male with an average age of 31.8 +/- 12.6. Involved sites included eight disseminated cases, six central nervous system, four lungs, one abdomen and one soft tissue. IFI contributed to a high mortality with 10 deaths (50%), and there were no survivors for the disseminated cases and Candida-infected patients. High activity (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) > 8) was noted in 50% of IFI episodes. The survival from IFI diagnosis to death was only 7.7 +/- 4.2 days, all in a rapid course. No statistical difference was found between survivors and non-survivors when comparing their SLEDAI. Eighty-five percent of IFI episodes under high dosages of corticosteroids therapy and 95% of patients had lupus nephritis. There was an increased risk of IFI in the lupus patients receiving high daily dosage of prednisolone therapy. Critical information from analyses of the present large series could be applied into clinical practices to reduce the morbidity and mortality in such patients.

Serious pulmonary toxicity in patients with Hodgkin's lymphoma with SGN-30, gemcitabine, vinorelbine, and liposomal doxorubicin is associated with an FcγRIIIa-158 V/F polymorphism.

BACKGROUND: Based on in vitro synergistic cytotoxicity when anti-CD30 antibodies are combined with gemcitabine, the Cancer and Leukemia Group B conducted a double-blind, randomized, phase II trial of SGN-30 with gemcitabine, vinorelbine, and pegylated liposomal doxorubicin (GVD) in patients with relapsed Hodgkin's lymphoma. PATIENTS AND METHODS: In part 1 of the trial, 16 patients received SGN-30 with GVD to assess the safety of the combination. In part 2, patients were randomly allocated to SGN-30 (n = 7) or placebo (n = 7) with GVD to determine overall response rate (ORR). RESULTS: ORR in all 30 patients was 63% (65% with SGN-30 plus GVD, n = 23, and 57% with placebo plus GVD, n = 7). Median event-free survival was 9.0 months, with no difference between the two arms. Grades 3-5 pneumonitis occurred in five patients receiving SGN-30 and GVD, leading to premature closure of the trial. All five patients with pulmonary toxicity had a V/F polymorphism in the FcγRIIIa gene (P = 0.008). CONCLUSIONS: Together with historical data demonstrating a 2% incidence of pulmonary events with GVD, these results indicate that SGN-30 cannot safely be administered concurrently. The risk of pneumonitis with SGN-30 and GVD is greatest in patients with an FcγRIIIa V/F polymorphism.

Vascular stents in the management of portal venous complications in living donor liver transplantation.

To evaluate the efficacy of stent placement in the treatment of portal vein (PV) stenosis or occlusion in living donor liver transplant (LDLT) recipients, 468 LDLT records were reviewed. Sixteen (10 PV occlusions and 6 stenoses) recipients (age range, 8 months-59 years) were referred for possible interventional angioplasty (dilatation and/or stent) procedures. Stent placement was attempted in all. The approaches used were percutaneous transhepatic (n = 10), percutaneous transsplenic (n = 4), and intraoperative (n = 2). Technical success was achieved in 11 of 16 patients (68.8%). The sizes of the stents used varied from 7 mm to 10 mm in diameter. In the five unsuccessful patients, long-term complete occlusion of the PV with cavernous transformation precluded catherterization. The mean follow-up was 12 months (range, 3-24). The PV stent patency rate was 90.9% (10/11). Rethrombosis and occlusion of the stent and PV occurred in a single recipient who had a cryoperserved vascular graft to reconstruct the PV during the LDLT operation. PV occlusion of >1 year with cavernous transformation seemed to be a factor causing technical failure. In conclusion, early treatment of PV stenosis and occlusion by stenting is an effective treatment in LDLT. Percutaneous transhepatic and transsplenic, and intraoperative techniques are effective approaches depending on the situation.

Management guidelines for the use of alemtuzumab in chronic lymphocytic leukemia.

The consensus views of an expert roundtable meeting are presented as updated management guidelines for using alemtuzumab in chronic lymphocytic leukemia. Since the publication of previous management guidelines in 2004, clinical experience with alemtuzumab has grown significantly, especially regarding its efficacy and safety, management of cytomegalovirus (CMV) reactivation, identification of patient subgroups likely to benefit from alemtuzumab therapy and subcutaneous administration of alemtuzumab. The updated recommendations include (1) alemtuzumab monotherapy can be safely used as first-line therapy; (2) suitable patient subgroups for alemtuzumab therapy include elderly patients, patients with 17p deletion, patients with refractory autoimmune cytopenias and patients with profound pancytopenia at baseline due to heavily infiltrated bone marrow; (3) alemtuzumab treatment should be continued for 12 weeks (36 doses) whenever possible, and bone marrow examination may be considered at week 12 to evaluate response; (4) monitoring CMV reactivation by weekly PCR is mandated during therapy; when CMV reactivation becomes symptomatic or viremia increases, alemtuzumab therapy should be interrupted and anti-CMV therapy started; (5) subcutaneous administration is safe, easy to perform and appears equally effective compared with intravenous infusion and (6) our strong recommendation is that alemtuzumab combination therapy and consolidation therapy shall not be used outside carefully controlled clinical studies.

Liver graft regeneration in right lobe adult living donor liver transplantation.

Optimal portal flow is one of the essentials in adequate liver function, graft regeneration and outcome of the graft after right lobe adult living donor liver transplantation (ALDLT). The relations among factors that cause sufficient liver graft regeneration are still unclear. The aim of this study is to evaluate the potential predisposing factors that encourage liver graft regeneration after ALDLT. The study population consisted of right lobe ALDLT recipients from Chang Gung Memorial Hospital-Kaohsiung Medical Center, Taiwan. The records, preoperative images, postoperative Doppler ultrasound evaluation and computed tomography studies performed 6 months after transplant were reviewed. The volume of the graft 6 months after transplant divided by the standard liver volume was calculated as the regeneration ratio. The predisposing risk factors were compiled from statistical analyses and included age, recipient body weight, native liver disease, spleen size before transplant, patency of the hepatic venous graft, graft weight-to-recipient weight ratio (GRWR), posttransplant portal flow, vascular and biliary complications and rejection. One hundred forty-five recipients were enrolled in this study. The liver graft regeneration ratio was 91.2 +/- 12.6% (range, 58-151). The size of the spleen (p = 0.00015), total portal flow and GRWR (p = 0.005) were linearly correlated with the regeneration rate. Patency of the hepatic venous tributary reconstructed was positively correlated to graft regeneration and was statistically significant (p = 0.017). Splenic artery ligation was advantageous to promote liver regeneration in specific cases but splenectomy did not show any positive advantage. Spleen size is a major factor contributing to portal flow and may directly trigger regeneration after transplant. Control of sufficient portal flow and adequate hepatic outflow are important factors in graft regeneration.

A phase I/II study of rituximab and etanercept in patients with chronic lymphocytic leukemia and small lymphocytic lymphoma.

Rituximab has modest activity in relapsed chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma but is associated with tumor necrosis factor-alpha (TNF-alpha) release that can cause CLL proliferation and inhibit apoptosis. We examined whether disruption of TNF-alpha by etanercept improves response to rituximab in CLL. Eligible patients had previously treated CLL with performance status 0-3. Patients received etanercept 25 mg subcutaneously twice weekly (weeks 1-5) and rituximab 375 mg/m(2) intravenously thrice weekly (weeks 2-5) using a phase I/II design. Primary end points were response and toxicity. The 36 enrolled patients had a median of two prior treatments; 50% were fludarabine refractory and 22% had del(17p13.1). Of the 34 response-evaluable patients, 10 (29%) responded, including 9 partial responses and 1 complete remission. Response was not affected by prior rituximab or fludarabine-refractory status, but no patients with del(17p13.1) responded. Median progression-free survival for responders was 9.0 months (range 1-43). Ten patients have had treatment-free intervals exceeding 12 months, including four who have remained untreated for 32, 43, 46 and 56 months. Adverse events were mild, including mild infusion reactions, transient cytopenias and grade 3 infections in 14% of the patients. The combination of etanercept and thrice weekly rituximab produces durable remissions in non-del(17p13.1) CLL patients and is well tolerated.

Epidemiological evidence of altered cardiac autonomic function in overweight but not underweight subjects.

BACKGROUND: Little is known about the altered cardiac autonomic function (CAF) across different levels of body mass index (BMI), including underweight, normal weight, overweight and obesity. This study provides a thorough analysis to clarify the CAF change in subjects with underweight, overweight and obesity. METHODS: According to the World Health Organization (WHO) Asia-Pacific BMI cutoffs, a total of 1437 participants were classified as underweight (n=74), normal weight (n=588), overweight (n=313), obesity I (n=390) and obesity II (n=72). CAF was determined by standard deviation of normal-to-normal (SDNN) intervals or RR intervals, power spectrum in low (LF) and high frequency (HF) (LF, 0.04-0.15 Hz; HF, 0.15-0.40 Hz), and LF/HF ratio at supine for 5 min, the ratio between the 30th and the 15th RR interval after standing from the supine position (30/15 ratio) and the average heart-rate change while taking six deep breaths in 1 min (HR(DB)). RESULTS: There were significant differences in age, gender, socioeconomic status, blood pressure, HOMA insulin resistance index, fasting glucose, cholesterol, triglyceride and high-density lipoprotein (HDL)-C, and the prevalence of hypertension, ischemic/left bundle branch block (LBBB) electrocardiography (EKG) pattern, current smoking and alcohol use among subjects with underweight, normal weight, overweight, obesity I and II. Univariate analysis showed that SDNN, HR(DB), HF power and the square root of the LF/HF ratio differed among these five groups. Multivariate analysis showed that obesity I and II were inverse correlates of HR(DB) and HF power. Overweight, obesity I and II were positively associated with the square root of the LF/HF ratio. No BMI status was related to SDNN, 30/15 ratio or LF power. Underweight was not the independent correlate of any CAF indices. CONCLUSIONS: The risk for altered CAF is significant in overweight and obese subjects, independent of cardiovascular risk factors. Underweight is not apparently associated with CAF change.

Alemtuzumab (Campath-1H) in the treatment of chronic lymphocytic leukemia.

Alemtuzumab (Campath-1H) is a humanized IgG1 monoclonal antibody that targets the human CD52 antigen. CD52 is expressed by a variety of lymphoid neoplasms and most human mononuclear cell subsets. In 2001, alemtuzumab was approved for marketing in the United States and Europe for use in patients with fludarabine-refractory chronic lymphocytic leukemia (CLL). In heavily pretreated patients with CLL, the overall response rate (ORR) is approximately 35%, and in previously untreated patients the ORR is greater than 80%, with a recent randomized study suggesting it is superior to alkylator-based therapy. Importantly, alemtuzumab is effective in patients with high-risk del(17p13.1) and del(11q22.3) CLL. Alemtuzumab combination studies with fludarabine and/or monoclonal antibodies such as rituximab have demonstrated promising results. Alemtuzumab is also being studied in CLL patients as consolidation therapy for treatment of minimal residual disease, in preparation for stem cell transplantation and to prevent acute and chronic graft versus host disease. Alemtuzumab is frequently associated with acute 'first-dose' reactions when administered intravenously, but is much better tolerated when administered subcutaneously without loss of therapeutic efficacy. Additional potential adverse events associated with alemtuzumab administration include myelosuppression as well as profound cellular immune dysfunction with the associated risk of viral reactivation and other opportunistic infections. Additional studies detailing the mechanism of action of alemtuzumab as well as new strategies for prevention of opportunistic infections will aid in the future therapeutic development of this agent.

Active immunization to prevent de novo hepatitis B virus infection in pediatric live donor liver recipients.

This study aims to evaluate the efficacy of HBV vaccination as an alternative preventive measure against de novo HBV infection in pediatric living donor liver transplantation (LDLT). Sixty recipients were enrolled in this study. Thirty received grafts from anti-HBc(+) donors, and another 30 received grafts from anti-HBc(-) donors. HBV vaccine was given pretransplant to every candidate. Posttransplant, lamivudine was routinely given to recipients receiving anti-HBc(+) grafts for about 2 years. Forty-seven (78%) recipients achieved high levels of anti-HBs titer (>1000 IU/L). Two (3.3%) recipients developed de novo HBV infection where one received an anti-HBc(-) graft and another received an anti-HBc(+) graft. Both recipients were in the lower anti-HBs titer group (<1000 IU/L). The incidence of de novo HBV infection was significantly higher in the lower titer group (15.4% vs. 0%, p = 0.04). The median follow-up period was 51 months in recipients with anti-HBc(-) grafts and 57 months in those with anti-HBc(+) grafts. Active immunization is an effective method to prevent de novo HBV infection. It can result in high levels of anti-HBs titer (>1000 IU/L) which may prevent de novo HBV infection in pediatric patients with efficient primary vaccination undergoing LDLT.