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Background: The purpose of this experiment was to investigate the interactions of the local anesthetic lidocaine combined with an agent (serotonin or dopamine) as infiltrative anesthetics., Methods: Cutaneous analgesia was characterized by the blockade of the cutaneous trunci muscle reflex following 6 skin pinpricks on the rat back. Serotonin or dopamine at producing cutaneous analgesia in a dosage-dependent fashion was compared with lidocaine. Drug-drug interactions were calculated using the isobolographic analysis., Results: We revealed that serotonin, dopamine, and lidocaine provoked dose-related cutaneous analgesic effects. On the 50% effective dose basis, the rank of drugs' potency was found to be serotonin (1.70 [1.56-1.85] μmol) > lidocaine (5.18 [4.67-5.75] μmol) > dopamine (43.0 [40.9-45.2] μmol) (P < 0.01). At doses equivalent to their 25%, 50%, and 75% effective doses, serotonin or dopamine elicited a longer duration of action than lidocaine (P < 0.01) on producing cutaneous analgesia. Coadministration of serotonin or dopamine with lidocaine produced a synergistic effect., Conclusions: The preclinical data showed that serotonin and dopamine produce dose-related cutaneous analgesic effects as an infiltrative anesthetic. Serotonin has a better potency with a much longer duration of action compared with lidocaine at provoking cutaneous analgesia. Serotonin or dopamine as an adjuvant increases the quality of lidocaine in cutaneous analgesia.

Background: High blood pressure is related to cardiovascular diseases. We aimed to explore the interactions of methylenetetrahydrofolate reductase (MTHTR) gene C677T and A1298C mutations and folate/homocysteine (Hcy) status on blood pressure in a Chinese hypertensive population., Methods: The clinical data in the present study derived from a previous trial (NCT00520247). Genotypes in Hcy pathway enzymes were detected by PCR-RFLP methods. Supine blood pressure was measured with a mercury sphygmomanometer. Serum Hcy was measured by high-performance liquid chromatography, and serum folate was measured by chemiluminescent immunoassay., Results: This study showed that hyperhomocysteinemia independently elevated diastolic blood pressure (DBP) (β (SE): 2.02 (0.85), p = 0.018). Furthermore, individuals with high Hcy and MTHFR1298AC + CC genotypes showed higher DBP than the normal Hcy and 1298AA carriers (β (SE): 1.81 (0.54), p = 0.001). This correlation was verified by the trend test (p = 0.003). However, polymorphisms of MTHFR C677T, MTR A2756G or MTRR A66G do not affect baseline blood pressure level., Conclusions: The present study demonstrated that the MTHFR A1298C mutation accompanied by hyperhomocysteinemia jointly elevated DBP. Further studies are necessary to confirm the role of these genotypes and Hcy on blood pressure in a larger population.

Background: Gut dysbiosis may contribute to pain and bloating in patients with functional gastrointestinal disease., Aims: To determine if treatment with rifaximin would improve the symptoms of functional dyspepsia in Chinese patients in a double-blinded, randomised, placebo-controlled trial., Methods: Consecutive subjects with a diagnosis of functional dyspepsia as per the Rome III criteria were randomised to receive rifaximin 400 mg or placebo, all taken three times daily for 2 weeks. The investigators and study subjects were blinded to the treatment allocation. Subjects were followed up for 8 weeks. The primary end point was adequate relief of global dyspeptic symptoms (GDS). Secondary endpoints were relief of individual dyspeptic symptoms., Results: Eighty-six subjects were recruited. At week 8, there were significantly more subjects in the rifaximin than in the placebo group who experienced adequate relief of GDS (78% vs. 52%, P = 0.02). A trend favouring rifaximin group was also noted in the preceding 4 weeks. Rifaximin was also superior to placebo in providing adequate relief of belching and post-prandial fullness/bloating (PPF) in subjects at week 4. Subgroup analysis revealed that female subjects had more significant response to rifaximin treatment (adequate relief of GDS at week 4: 76% vs. 42%, P = 0.006; week 8: 79% vs. 47%, P = 0.008), as well as improvements in their belching and PPF at week 4. The incidences of adverse effects were similar in both groups., Conclusions: Treatment with 2 weeks of rifaximin led to adequate relief of global dyspeptic symptoms, belching and post-prandial fullness/bloating in subjects with functional dyspepsia. The difference was more marked in females. (clinicaltrials.org NCT01643083)., (© 2017 John Wiley & Sons Ltd.)

Objectives: Hepatitis B core-related antigen (HBcrAg) is a novel serum marker that correlates with intrahepatic hepatitis B virus (HBV) activity. Its association with HBV reactivation in hepatitis B surface antigen (HBsAg)-negative antibody to hepatitis B core antigen (anti-HBc)-positive patients undergoing high-risk immunosuppressive therapy is undefined., Methods: HBcrAg was measured in HBsAg-negative, anti-HBc-positive Asian patients with undetectable HBV DNA, who participated in two prospective studies investigating HBV reactivation during rituximab-containing chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). Patients were monitored every 4 weeks for up to 2 years, with entecavir started when HBV reactivation, defined as HBV DNA ≥10 IU ml -1 , developed., Results: One hundred and twenty-four HBsAg-negative, anti-HBc-positive patients (rituximab, N=62; allogeneic HSCT, N=62) with a median follow-up of 64 weeks (range: 4-104 weeks) were studied. HBV reactivation occurred in 31 patients, with a 2-year cumulative reactivation rate of 40.4%. Serum HBcrAg was detected in 43 (34.7%) patients. Baseline HBcrAg positivity was significantly associated with HBV reactivation (P=0.004, hazard ratio (HR): 2.94, 95% confidence interval (95% CI): 1.43-6.07). HBcrAg-positive patients had a significantly higher 2-year HBV reactivation rate than HBcrAg-negative patients (71.8 vs. 31%, P=0.002). In the rituximab cohort, the HRs for positive HBcrAg and negative antibody to HBsAg for HBV reactivation were 3.65 and 2.84, respectively (P=0.011, 95% CI: 1.35-9.86 and P=0.032, 95% CI: 1.10-7.37, respectively)., Conclusions: Serum HBcrAg positivity is a significant risk factor of HBV reactivation in HBsAg-negative, anti-HBc-positive patients undergoing high-risk immunosuppressive therapy and can potentially have a role in identifying patients who will best benefit from prophylactic nucleoside analogue treatment.

Size-complementary cyclotriveratrylene (CTV)-based hosts can incarcerate C 76 , C 78 , and C 84 , thus allowing the selective isolation of these higher-order fullerenes from a commercially available mixture of fullerenes. The hemicarceplexes, formed after the encapsulation of the size-complementary fullerenes within the hosts, are isolated by column chromatography and released at elevated temperature, thereby leading to the isolation of C 76 /C 78 and C 84 in good purities (up to 95 and 88 %, respectively)., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Studies have shown that postdischarge care for self-harm patients is effective in reducing repeated suicidal behaviors. Little is known about whether volunteer support can help reduce self-harm repetition and improve psychosocial well-being., Aim: This study investigated the efficacy of volunteer support in preventing repetition of self-harm., Method: This study used a quasi-experimental design by assigning self-harm patients admitted to the emergency departments to an intervention group with volunteer support and treatment as usual (TAU) for 9 months and to a control group of TAU. Outcome measures include repetition of self-harm, suicidal ideation, hopelessness, and level of depressive and anxiety symptoms., Results: A total of 74 cases were recruited (38 participants; 36 controls). There were no significant differences in age, gender, and clinical condition between the two groups at the baseline. The intervention group showed significant improvements in hopelessness and depressive symptoms. However, the number of cases of suicide ideation and of repetition of self-harm episodes was similar for both groups at the postintervention period., Conclusion: Postdischarge care provided by volunteers showed significant improvement in hopelessness and depression. Volunteers have been commonly involved in suicide prevention services. Further research using rigorous methods is recommended for improving service quality in the long term.

Background: Factors influencing changes in liver stiffness measurements during long-term nucleoside analogue therapy for chronic hepatitis B (CHB) have not been thoroughly investigated., Aim: To identify determinants of on-treatment fibrosis regression in CHB., Methods: We performed follow-up liver stiffness and controlled attenuation parameter measurements on nucleoside analogue-treated CHB patients with severe liver fibrosis, according to EASL-ALEH criteria, diagnosed by transient elastography in 2006-2008. Anthropometric measurements and different metabolic parameters were recorded., Results: Among 257 patients with severe liver fibrosis by initial transient elastography, 123 (47.9%) were recruited for reassessment. Median treatment duration was 87.5 (interquartile range 75.3-102.2) months; 97.5% had undetectable HBV DNA. There was a significant reduction in median liver stiffness from 14.6 to 8.3 kPa (P < 0.001). A total of 29.3% had fibrosis regression, with lower rates of 17.9%, 14.9% and 11.5% noted in patients with body-mass index (BMI) ≥25 kg/m 2 , metabolic syndrome and diabetes, respectively. Absence of BMI ≥25 kg/m 2 , diabetes and metabolic syndrome, when compared with presence of any one of these three factors, was associated with increased fibrosis regression (43.1% vs. 16.9%, P = 0.001). Multivariate analysis found a lower BMI to be the only factor independently associated with fibrosis regression (P = 0.034, odds ratio 0.68, 95% CI 0.48-0.97). No association was noted between controlled attenuation parameter measurements and fibrosis regression (P > 0.05)., Conclusion: An increased BMI hindered fibrosis regression in patients with chronic hepatitis B during nucleoside analogue treatment, suggesting that control of metabolic risk factors, in addition to virologic suppression via antiviral therapy, might be needed to halt the fibrogenic process in chronic hepatitis B., (© 2016 John Wiley & Sons Ltd.)

Tricyclic antidepressants (TCAs) are found to have an analgesic action for relieving cutaneous pain associated with neuropathies. The aim of this study was to assess cutaneous absorption and analgesia of topically applied TCAs. Percutaneous delivery was investigated using nude mouse and pig skin models at both infinite and saturated doses. We evaluated the cutaneous analgesia in nude mice using the pinprick scores. Among five antidepressants tested in the in vitro experiment, mesoridazine, promazine and doxepin showed a superior total absorption percentage. The drug with the lowest total absorption percentage was found to be fluphenazine (<7%) either at an infinite dose or at saturated solubility. The follicular pathway was important for mesoridazine and promazine delivery. Mesoridazine showed stronger skin analgesia than the other TCAs although the in vivo skin absorption of mesoridazine (0.34nmol/mg) was less than that of promazine (0.80nmol/mg) and doxepin (0.74nmol/mg). Mesoridazine had a prolonged duration of pain relief (165min) compared to promazine (83min) and doxepin (17min). The skin irritation test demonstrated an evident barrier function deterioration and cutaneous erythema by promazine and doxepin treatment, whereas mesoridazine caused no obvious adverse effect by topical application for up to 7days., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Hepatitis B surface antigen (HBsAg) seroclearance is the recommended treatment end point for nucleoside analogue (NA) therapy in chronic hepatitis B, yet the underlying kinetics and durability of HBsAg seroclearance in NA-treated patients have not been well described., Methods: We compared the HBsAg kinetics and long-term serologic outcomes of 51 chronic hepatitis B patients achieving HBsAg seroclearance during NA therapy with those of 51 HBsAg-positive controls, matched for age, sex, hepatitis B e antigen status, NA type, and treatment duration. Viral profiles before and after HBsAg seroclearance during and after NA treatment cessation were determined., Results: The median time to HBsAg seroclearance and the median follow-up duration after HBsAg seroclearance were 61.2 and 51.6 months respectively. Patients achieving HBsAg seroclearance maintained high median rates of HBsAg reduction throughout therapy (first 6 months, 0.40 IU/mL/year; after year 1, 0.39 IU/mL/year; p = 0.809). For controls, the median rate of HBsAg reduction was significantly slower with time (first 6 months and after year 1, 0.19 and 0.05 IU/mL/year; p = 0.006). The difference in the median HBsAg reduction rates after year 1 between the two groups was significant (p < 0.001). The cumulative rates of antibody to HBsAg development and HBsAg seroreversion 72 months after HBsAg seroclearance were 68.9 and 8.3% (one patient receiving immunosuppressive therapy; one patient with pre-S/S variant), respectively. Among 22 patients who discontinued therapy after HBsAg seroclearance, 21 remained HBsAg negative with undetectable hepatitis B virus DNA and one patient with reactivation had the pre-S/S variant., Conclusion: NA-treated patients achieving HBsAg seroclearance uniquely maintained high rates of HBsAg reduction throughout treatment, with HBsAg seroclearance durable in most of the patients after treatment cessation.

Background & Aims: Serologic profiles after hepatitis B surface antigen (HBsAg) seroclearance in chronic hepatitis B (CHB) have not been well-studied., Methods: We employed a highly sensitive HBsAg (hs-HBsAg) assay (lower detection limit 0.5 mIU/ml), 100 times more sensitive than conventional HBsAg measurements. CHB patients achieving HBsAg seroclearance defined by conventional assays were followed up for serum hs-HBsAg, HBV DNA and antibody to HBsAg (anti-HBs) levels at 0 months, 6-12 months and 3-5 years after HBsAg seroclearance. Factors associated with hs-HBsAg detectability were determined., Results: One hundred and nine patients were recruited; 94 (86.2%) were followed up to years 3-5; and 25 patients (22.9%) were on nucleoside analogue therapy for a median duration of 6.0 (range 1.5-12.7) years before HBsAg seroclearance. Detectable hs-HBsAg was noted in 88 (80.7%), 60 (55.0%) and 20 (21.3%) patients at 0 months, 6-12 months and 3-5 years respectively. At years 3-5, genotype B patients, when compared to genotype C patients, had a higher anti-HBs positive rate (63.2% and 41.1% respectively, P = 0.036). Serum anti-HBs positivity, when compared to persistent anti-HBs negativity, was associated with a lower rate of hs-HBsAg detection (7.4% and 40% respectively, P < 0.001). Multivariate analysis showed anti-HBs negativity at years 3-5 to be independently associated with persistently positive hs-HBsAg (P = 0.007, odds ratio 7.1, 95% confidence interval 1.7-29.3)., Conclusion: Serum hs-HBsAg could detect HBsAg presence in a substantial proportion of CHB after HBsAg seroclearance defined by conventional assays, especially among anti-HBs negative individuals. Serum hs-HBsAg could potentially assist differentiating HBsAg-negative CHB from individuals with only past HBV exposure without carrier state., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Clonidine prolongs duration of analgesia when used as an adjunct to local anesthetics for infiltrative cutaneous analgesia, and propranolol produces local anesthesia. The purpose of the experiment was to evaluate clonidine as an adjuvant for propranolol on the quality and duration of cutaneous analgesia. A rat model of cutaneous trunci muscle reflex (CTMR) in response to local skin pinprick was employed to evaluate the cutaneous analgesic effect of propranolol combined with clonidine. The long-lasting local anesthetic bupivacaine was used as control. Cutaneous analgesia elicited by propranolol and bupivacaine was dose-dependent, and both propranolol (9.0μmol) and bupivacaine (1.8μmol) produced 100% nociceptive blockade. On an 50% effective dose (ED50) basis, the relative potency was bupivacaine [0.48 (0.42-0.55) μmol] greater than propranolol [2.27 (1.98-2.54) μmol] (p<0.01). Subcutaneous saline and clonidine (0.12μmol) did not produce cutaneous analgesia. The mixture of an ineffective-dose clonidine (0.12μmol) and a drug (propranolol or bupivacaine) at ED50 or ED95 increased the potency and extended the duration at producing cutaneous analgesia. The resulting data demonstrated that propranolol is less potent than bupivacaine as an infiltrative anesthetic. Clonidine as an adjuvant for propranolol or bupivacaine has a significant peripheral action in increasing the depth and duration of action on infiltrative cutaneous analgesia., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Preoperative end-stage renal disease carries a high mortality and morbidity risk after aortic valve replacement (AVR), but the effect of renal insufficiency remains to be clarified. Through propensity score analysis, we compared the preoperative demographics, perioperative profiles, and outcomes between patients with and without renal insufficiency. From August 2005 to November 2014, 770 adult patients underwent AVR in a single institution. Patients were classified according to their estimated glomerular infiltration rate (eGFR) as renal insufficiency (eGFR: 30-89 mL/min/1.73 m) or normal (eGFR, ≥90 mL/min/1.73 m). Propensity scoring was performed with a 1:1 ratio, resulting in a matched cohort of 88 patients per group. Demographics, comorbidities, and surgical procedures were well balanced between the 2 groups, except for diabetes mellitus and eGFR. Patients with renal insufficiency had higher in-hospital mortality (19.3% versus 3.4%, P < 0.001), a greater need for postoperative hemodialysis (14.8% versus 3.1%, P = 0.009), and prolonged intubation times (>72 hour; 25% versus 9.1%, P = .008), intensive care unit stays (8.9 ± 9.9 versus 4.9 ± 7.5 days, P = .046), and hospital stays (35.3 ± 31.7 versus 24.1 ± 20.3 days, P = .008), compared with those with normal renal function. Multivariate analysis confirmed that preoperative renal insufficiency was an in-hospital mortality predictor (odds ratio, 2.33; 95% confidence interval, 1.343-4.043; P = .003), as were prolonged cardiopulmonary bypass time, intraaortic balloon pump support, and postoperative hemodialysis. The 1-year survival significantly differed between the 2 groups including (normal 87.5% versus renal insufficiency 67.9%, P < .001) or excluding in-hospital mortality (normal 90.7% versus renal insufficiency 82.1%, P = .05). Patients with preoperative renal insufficiency who underwent AVR had higher in-hospital mortality rates and increased morbidities, especially those associated with hemodynamic instabilities requiring intraaortic balloon pump support or hemodialysis. Earlier surgical intervention for severe aortic valve disease should be considered in patients who show deteriorating renal function during follow-up.

Proteins synthesized in the endoplasmic reticulum (ER) are properly folded with the assistance of ER chaperones. Accumulation of misfolded protein in the ER triggers an adaptive ER stress (ERS) response termed the unfolded protein response. Recent interest has focused on the possibility that the accumulation of misfolded proteins can also contribute to reproductive response, including preimplantation embryos, testicular germ cell, placenta, and unexplained intrauterine growth restriction (IUGR). The major ERS pathway constituents are present at all stages of preimplantation development and that the activation of ERS pathways can be induced at the 8-cell, morula and blastocyst stage. This review mainly introduced the research progress of ERS induced apoptosis of reproductive cells, providing a new direction for the research of reproductive disease therapy., (Copyright © 2016 The Editorial Board of Journal of Reproduction and Contraception. Published by Elsevier (Singapore) Pte Ltd. All rights reserved.)

Purpose: This study reviews our 17-year experience of managing blunt traumatic aortic injury (BTAI)., Methods: We analyzed information collected retrospectively from a tertiary trauma center., Results: Between October 1995 and June 2012, 88 patients (74 male and 14 female) with a mean age of 39.9 ± 17.9 years (range 15-79 years) with proven BTAI were enrolled in this study. Their GCS, ISS, and RTS scores were 12.9 ± 3.7, 29.2 ± 9.8, and 6.9 ± 1.4, respectively. Twenty-one (23.8 %) patients were managed non-operatively, 49 (55.7 %) with open surgical repair, and 18 (20.5 %) with endovascular repair. The in-hospital mortality rate was 17.1 % (15/81) and there were no deaths in the endovascular repair group. The mean follow-up period was 39.9 ± 44.2 months. The survivors of blunt aortic injury had lower ISS, RTS, TRISS, and serum creatinine level and lower rate of massive blood transfusion, shock, and intubation than the patients who died, despite higher rates of endovascular repair, hemoglobin, and GCS on presentation. The degree of aortic injury, different therapeutic options, GCS, shock presentation, and intubation on arrival all had significant impacts on outcome., Conclusions: Shock, aortic injury severity, coexisting trauma severity, and different surgical approaches impact survival. Endovascular repair achieves a superior mid-term result and is a reasonable option for treating BTAI.

Gastric cancer (GC) is one of the leading causes of cancer related death in the world, particularly in East Asia. According to the Correa's cancer cascade, non-cardia GC is usually developed through a series of mucosal changes from non-atrophic gastritis to atrophic gastritis (AG), intestinal metaplasia (IM), dysplasia and adenocarcinoma. Atrophic gastritis and IM are therefore generally considered to be pre-neoplastic gastric lesions. Helicobacter pylori (H. pylori) infection is an important initiating and promoting step of this gastric carcinogenesis cascade. Emerging long-term data showed that eradication of H. pylori reduced the risk of subsequent cancer development. It however remains confusing whether eradication of the bacterium in individuals with pre-neoplastic gastric lesions could regress these changes as well as in preventing cancer. Whilst H. pylori eradication could likely regress AG, the presence of IM may be a point of no return in this cascade. Hence, surveillance by endoscopy may be indicated in those with extensive IM or those with incomplete IM, particularly in populations with high GC risk. The optimal interval and the best tool of surveillance endoscopy remains to be determined in future studies.

Surgery for aortic dissections or aneurysms can be extended into the aortic arch by hemiarch replacement (HAR) or total arch replacement (TAR). Although cardiovascular surgeons have been performing HAR and TAR for decades, the mechanical properties of HAR and TAR are not well understood. This study investigates the mechanical behaviors and stress distributions in HAR and TAR using a hybrid fluid-structure interaction analysis that combines computational fluid dynamics and structural static analysis. Geometrical information on the aortas of 11 subjects was extracted from contrast-enhanced computed tomography (CT) scan data. The CT images were imported into medical image processing software to reconstruct 3D models of the aortas. A 3D finite element model was employed to simulate aortas that receive HAR or TAR. The deformation of the great vessels and the stress distributions at both the vessels and the aortic grafts were calculated. The numerical results revealed that the aortas following TAR exhibited a lower level of stress than those following HAR. Higher stresses may cause arterial wall injury and increase the risk of rupture. Finite element analysis of the aortas and the aortic grafts provides useful information that helps physicians better understand the potential problems that may arise after various surgical procedures.

Although memantine blocks sodium currents and produces local skin anesthesia, spinal anesthesia with memantine is unknown. The purpose of the study was to evaluate the local anesthetic effect of memantine in spinal anesthesia and its comparison with a widely used local anesthetic lidocaine. After intrathecally injecting the rats with five doses of each drug, the dose-response curves of memantine and lidocaine were constructed. The potencies of the drugs and durations of spinal anesthetic effects on motor function, proprioception, and nociception were compared with those of lidocaine. We showed that memantine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED50 ) basis, the rank of potency was lidocaine greater than memantine (P < 0.05 for the differences). At the equipotent doses (ED25 , ED50 , ED75 ), the block duration produced by memantine was longer than that produced by lidocaine (P < 0.05 for the differences). Memantine, but not lidocaine, displayed more sensory/nociceptive block than motor block. The preclinical data demonstrated that memantine is less potent than lidocaine, whereas memantine produces longer duration of spinal anesthesia than lidocaine. Memantine shows a more sensory-selective action over motor blockade., (© 2015 Société Française de Pharmacologie et de Thérapeutique.)

Background: Thoracic endovascular aortic repair (TEVAR) is a rapidly evolving therapy in treating blunt traumatic aortic injury (TAI). However, currently there is no consensus among literature regarding the repair timing of TAI. Our experiences to manage TAI with comparison between open surgical and endovascular repair in repair timing and short-term outcomes are reported. Risk factors for postoperative mortality and morbidity are stratified., Methods: Between January 2003 and February 2014, 63 consecutive patients who have suffered from TAI and underwent conventional open surgical or endovascular aortic repair were retrospectively reviewed in this study. The primary outcomes were in-hospital mortality, postoperative complication, and operation timing. All medical records regarding trauma mechanisms, concomitant injuries, intervention detail, and postoperative outcomes were reviewed and analyzed., Results: Among the 63 patients (mean age, 37.9 years; 57 male), 23 underwent open repair (OR) and 40 underwent TEVAR for blunt TAI. The TEVAR group had more urgent operation (injury to repair <24 hr; 57.5% vs. 30.4%, P = 0.038) and shorter operative time (136.25 ± 54.48 min vs. 414.78 ± 212.24 min, P = 0.00) than the respective open surgical repair group. Postoperative mortality and morbidity analysis showed that the OR group had higher in-hospital mortality (30.4% vs. 7.5%; P = 0.029), more patients with acute renal failure in need of hemodialysis (17.4% vs. 2.3%; P = 0.038), and more post-operation infection (30.4% vs. 5%; P = 0.005) than the respective TEVAR group. The Multivariate analysis, of the 10 (15.88%) patients that died after the surgery, showed that the risk factors of hospital mortality were grade IV TAI (frank rupture)., Conclusions: For treating TAI, TEVAR has emerged as a quicker and safer treatment option than OR. The findings of this study support the use of TEVAR over OR for patients who suffered from TAI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The nanofibrous biodegradable drug-loaded membranes that sustainably released recombinant human platelet-derived growth factor (rhPDGF-BB) to repair diabetic wounds were developed in this work.rhPDGF-BB and poly(lactic-co-glycolic acid) (PLGA) were mixed in hexafluoroisopropyl alcohol, followed by the electrospinning of the solutions into biodegradable membranes to equip the nanofibrous membranes. An elution technique and an enzyme-linked immunosorbent assay kit were used to determine the rhPDGF-BB release rates in vitro and in vivo from this membrane. Eighteen Sprague-Dawley streptozotocin-induced diabetic rats were randomized into 3 groups: rhPDGF-BB-loaded nanofibrous membrane group, PLGA only membrane group, and conventional gauze sponge group for the wound associated with diabetes of rat in each group.The nanofibrous biodegradable membranes released effective concentrations of rhPDGF-BB for over 21 days. The nanofibrous rhPDGF-BB-loaded PLGA membranes contained more water and were further hydrophilic than PLGA only fibers. The rhPDGF-BB-loaded PLGA membranes considerably helped the diabetic wounds repairing. Furthermore, the proliferative cells and angiogenesis of rats associated with diabetes by rhPDGF-BB-loaded nanofibrous membranes were greater than those of other groups, owing to the increased matrix metalloproteinase 9.These biodegradable rhPDGF-BB-loaded membranes were effective in treating diabetic wounds as very advanced accelerators during the initial phases of wound-healing process., Competing Interests: The authors have no conflicts of interest to disclose.

The purpose of the study was to estimate the ability of L-tyrosine to induce cutaneous analgesia and to investigate the interaction between L-tyrosine and the local anesthetic lidocaine. After subcutaneously injecting the rats with L-tyrosine and lidocaine in a dose-dependent manner, cutaneous analgesia (by blocking the cutaneous trunci muscle reflex-CTMR) was evaluated in response to the local pinprick. The drug-drug interaction was analyzed by using an isobolographic method. We showed that both L-tyrosine and lidocaine produced dose-dependent cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was lidocaine (5.09 [4.88-5.38] μmol)>L-tyrosine (39.1 [36.5-41.8] μmol) (P<0.05). At the equipotent doses (ED25, ED50, and ED75), the duration of cutaneous analgesia caused by L-tyrosine lasted longer than that caused by lidocaine (P<0.01). Lidocaine co-administered with L-tyrosine exhibited an additive effect on infiltrative cutaneous analgesia. Our pre-clinical study demonstrated that L-tyrosine elicits the local/cutaneous analgesia, and the interaction between L-tyrosine and lidocaine is additive. L-tyrosine has a lower potency but much greater duration of cutaneous analgesia than lidocaine. Adding L-tyrosine to lidocaine preparations showed greater duration of cutaneous analgesia compared with lidocaine alone., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Biofilm-forming bacteria are highly resistant to antibiotics, host immune defenses, and other external conditions. The formation of biofilms plays a key role in colonization and infection. To explore the mechanism of biofilm formation, mutant strains of Proteus vulgaris XC 2 were generated by Tn5 random transposon insertion. Only one biofilm defective bacterial species was identified from among 500 mutants. Inactivation of the glpC gene coding an anaerobic glycerol-3-phosphate dehydrogenase subunit C was identified by sequence analysis of the biofilm defective strain. Differences were detected in the growth phenotypes of the wild-type and mutant strains under pH, antibiotic, and organic solvent stress conditions. Furthermore, we observed an increase in the phagocytosis of the biofilm defective strain by the mouse macrophage RAW264.7 cell line compared to the wild-type strain. This study shows that the glpC gene plays an important role in biofilm formation, in addition to imparting pH, organic solvent, and antibiotic tolerance, and defense against phagocytosis to Proteus sp. The results further clarified the mechanism of biofilm formation at the genomic level, and indicated the importance of the glpC gene in this process. This data may provide innovative therapeutic measures against P. vulgaris infections; furthermore, as an important crocodile pathogen, this study also has important significance in the protection of Chinese alligators.

The physiological role of cystic fibrosis transmembrane conductance regulator (CFTR) in keratinocytes and skin wound healing is completely unknown. The present study shows that CFTR is expressed in the multiple layers of keratinocytes in mouse epidermis and exhibits a dynamic expression pattern in a dorsal skin wound healing model, with diminishing levels observed from day 3 to day 5 and re-appearing from day 7 to day 10 after wounding. Knockdown of CFTR in cultured human keratinocytes promotes cell migration but inhibits differentiation, while overexpression of CFTR suppresses migration but enhances differentiation, indicating an important role of CFTR in regulating keratinocyte behavior. In addition, we have demonstrated a direct association of CFTR with epithelial junction formation as knockdown of CFTR downregulates the expression of adhesion molecules, such as E-cadherin, ZO-1 and β-catenin, and disrupts the formation of cell junction, while overexpression of CFTR enhances cell junction formation. More importantly, we have shown that ΔF508cftr-/- mice with defective CFTR exhibit delayed wound healing as compared to wild type mice, indicating that normal function of CFTR is critical for wound repair. Taken together, the present study has revealed a previously undefined role of CFTR in regulating skin wound healing processes, which may have implications in injury repair of other epithelial tissues., (© 2015 Wiley Periodicals, Inc.)

Background: The purposes of this study were to evaluate the co-administration of clonidine with memantine and to determine whether it has a peripheral action in intensifying cutaneous analgesia., Methods: Cutaneous analgesia was examined through inhibition of the cutaneous trunci muscle reflex in response to the local noxious pinprick in rats. Effect of the added subcutaneous clonidine to memantine on infiltrative cutaneous analgesia was assessed and compared with the local anesthetic lidocaine., Results: On the 50% effective dose (ED50) basis, the rank of drug potency was memantine [4.05 (3.95-4.18) μmol]>lidocaine [5.81 (5.70-5.98) μmol] (p<0.01). Clonidine at a dose of 0.12 μmol did not elicit cutaneous analgesia. Mixtures of clonidine (0.12 μmol) with drug (memantine or lidocaine) at ED50 or ED95 prolonged the duration of action and enhanced the potency as infiltrative cutaneous analgesia. Clonidine enhanced the lidocaine cutaneous analgesia in which had a better effect than added to memantine., Conclusions: Our resulting data showed that memantine displayed more potent cutaneous analgesia than lidocaine. Co-administration of memantine or lidocaine with clonidine increased the potency and duration of the cutaneous analgesia. Clonidine intensified the effects of lidocaine promoting cutaneous analgesia than added to memantine., (Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

The purpose of this study is to develop biodegradable drug-eluting pellets to provide a sustainable delivery of cisplatin intrapleurally. Poly(d,l)-lactide-co-glycolide (PLGA) (LA:GA=50:50) copolymer and cisplatin were mixed, compressed, and sintered to construct biodegradable pellets and placed in phosphate-buffered saline to test the characteristics of in vitro release. In vivo, equal amounts of cisplatin (10mg/kg) were introduced into rabbit pleural cavities either by free form (Gr1) or pellets form (Gr2). Cisplatin concentrations in the collected pleural effusion and blood were measured and compared by repeated measurement ANOVA. In vitro, approximately 5% of the cisplatin was released in the first day while the rest was gradually released in the following 50 days. In vivo, the cisplatin level in the pleural fluid was equally high during the first 2 days but dropped quickly in Gr1 while remaining high in Gr2 for 18 days, the difference was statistically significant (P<0.001) In contrast, the plasma cisplatin level was 10 times significantly higher in Gr1 than in Gr2 (P<0.001), which resulted in two early deaths of rabbits. Thus we concluded that our biodegradable pellets could achieve high and steady cisplatin release in the pleural cavity. This novel drug delivery system may have the potential to serve as an adjuvant treatment for malignant pleural lesion., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background and Objective: The off-treatment durability of nucleos(t)ide analogue therapy in Asian hepatitis B e antigen (HBeAg) negative chronic hepatitis B (CHB) and the role of hepatitis B surface antigen (HBsAg) levels in predicting off-treatment durability has not been well investigated., Methods: Following Asia-Pacific Association for the Study of the Liver guidelines, entecavir was stopped in Asian HBeAg negative patients treated for ≥ 2 years with undetectable HBV DNA levels on ≥ 3 separate occasions 6 months apart before treatment cessation. HBsAg and HBV DNA levels were prospectively monitored every 6-12 weeks for 48 weeks. Entecavir was restarted if there was virologic relapse (defined as HBV DNA >2000IU/mL)., Result: 184 patients (mean age 53.9 years, 67.9% male) were recruited. The cumulative rate of virologic relapse at 24 and 48 weeks was 74.2% and 91.4%, respectively. The median HBV DNA level at virologic relapse was 11000 (range 2115 to >1.98×10(8)) IU/mL. 42 (25.8%) patients had elevated alanine aminotransferase (median level 97 U/L, range 37-1058 U/L) during virologic relapse. Mean rate of off-treatment HBsAg decline was 0.018 (± 0.456) log IU/mL/year. No patients cleared HBsAg. There was no correlation between off-treatment serial HBsAg and HBV DNA levels (r=-0.026, p=0.541). HBsAg levels at the time of entecavir commencement, entecavir cessation and the subsequent rate of HBsAg reduction were not associated with virologic relapse (all p>0.05)., Conclusions: Entecavir cessation in Asian HBeAg negative CHB resulted in high rates of virologic relapse, suggesting nucleos(t)ide analogue therapy should be continued indefinitely until the recognised treatment endpoint of HBsAg seroclearance., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: Patterns of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg) -negative, antihepatitis B core antigen antibody (anti-HBc) -positive patients with lymphoma receiving rituximab-containing chemotherapy have not been well described., Patients and Methods: HBsAg-negative, anti-HBc-positive Chinese patients with undetectable serum HBV DNA (< 10 IU/mL), diagnosed with hematologic malignancies and receiving rituximab-containing chemotherapy, were prospectively monitored every 4 weeks for up to 2 years. Entecavir was started when HBV reactivation (defined as detectable HBV DNA) was encountered., Results: Among 260 patients receiving rituximab-containing chemotherapy, 63 patients (24.2%) who were HBsAg negative and anti-HBc positive underwent follow-up for a median of 70 weeks (range, 6 to 104 weeks). The 2-year cumulative rate of HBV reactivation was 41.5%, occurring at a median of 23 weeks (range, 4 to 100 weeks) after rituximab treatment. The median HBV DNA level at reactivation was 43 IU/mL (range, 14 to 920 IU/mL). A baseline undetectable antibody to HBsAg (anti-HBs; < 10 mIU/mL) was the only significant risk factor that was positively associated with HBV reactivation (hazard ratio, 3.51; 95% CI, 1.37 to 8.98; P = .009). Patients with negative baseline anti-HBs, compared with those with positive anti-HBs, had a significantly higher 2-year cumulative rate of HBV reactivation (68.3% v 34.4%; P = .012). At HBV reactivation, all patients had normal ALT, and all patients but one were HBsAg negative. Entecavir successfully controlled HBV reactivation in all patients., Conclusion: A high rate of HBV reactivation was observed in HBsAg-negative, anti-HBc-positive patients undergoing rituximab-containing chemotherapy, with the risk of reactivation significantly higher in anti-HBs-negative patients. Periodic HBV DNA monitoring was an effective strategy in preventing HBV-related complications., (© 2014 by American Society of Clinical Oncology.)

Changes in two novel HBV serological markers, linearized hepatitis B surface antigen (HQ-HBsAg) and hepatitis B core-related antigen (HBcrAg), in the natural history of chronic hepatitis B (CHB) have not been well characterized. Serum HQ-HBsAg and HBcrAg levels of 404 Asian treatment-naïve CHB patients were analysed in a cross-sectional manner. Patients were categorized into five groups: immune tolerant (IT group, n=52), immune clearance (IC group, n=105), hepatitis B e antigen (HBeAg)-negative hepatitis (ENH group, n=97), HBeAg-negative quiescent group (ENQ group, n=95) and CHB with hepatitis B surface antigen (HBsAg) seroclearance (SC group, n=55). HQ-HBsAg and HBcrAg were measured and correlated with HBV DNA, HBsAg, HBV genotype and clinical parameters. HQ-HBsAg showed good correlation with HBsAg, especially in the ENQ group (r=0.874, p<0.001). Correlation of HQ-HBsAg with HBV DNA was less prominent and weakest in the ENH group (r=0.268, p 0.008). HBcrAg correlated best with HBV DNA in the ENQ group (r=0.537, p<0.001). In the ENQ group, 42.1% of patients had undetectable HBcrAg; this subgroup of patients, when compared with those with detectable HBcrAg, had significantly lower median HBV DNA (3.17/4.48 log IU/mL, p<0.001) and HBsAg (5.05/5.96 log mIU/mL, p<0.001) levels. Forty per cent of the SC group patients had detectable HQ-HBsAg and/or HBcrAg up to 42 months after HBsAg seroclearance. When comparing anti-HBs positivity and median time after HBsAg seroclearance in the SC group with and without detectable HQ-HBsAg/HBcrAg, there was no significant difference (22.7% and 36.4%, respectively, p 0.284, and 76.5 and 93.2 months, respectively, p 0.245). HQ-HBsAg and HBcrAg showed unique patterns of distribution throughout the five disease phases of CHB, including high detectability rates after HBsAg seroclearance, opening up different possibilities for their applicability., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

The aim of this study was to evaluate the effect of epinephrine as additive for propranolol as an infiltrative anesthetic. Using a rat model of cutaneous trunci muscle reflex (CTMR), we tested the effect of co-administration of epinephrine with propranolol on infiltrative cutaneous analgesia. Bupivacaine, a long-lasting local anesthetic, was used as control. Subcutaneous propranolol and bupivacaine elicited a dose-dependent local anesthetic effect on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the relative potency was bupivacaine [2.05 (1.95-2.21) μmol/kg]>propranolol [9.21 (9.08-9.42) μmol/kg] (P<0.01 for each comparison). Subcutaneous epinephrine (0.012 μmol/kg) did not produce cutaneous analgesia. Mixtures of epinephrine (0.012 μmol/kg) with drugs (propranolol or bupivacaine) at ED50 or ED95, respectively, intensified and prolonged drug action on infiltrative cutaneous analgesia. Intraperitoneal injection of combined drugs (propranolol or bupivacaine) at ED95 with epinephrine (0.012 μmol/kg) exhibited no cutaneous analgesia. We concluded that propranolol was less potent but produced a similar duration of action when compared to bupivacaine on infiltrative cutaneous analgesia. Epinephrine as adjuvant for propranolol or bupivacaine enhanced the potency and extended the duration of action on infiltrative cutaneous analgesia., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Aim: The aim of this study was to screen miRNAs related to different subtypes of breast cancer and their target genes to identify new markers of tumor subtype., Materials and Methods: The miRNA expression profiles of breast cancer GSE38867 including 7 ductal carcinoma in situ breast (DCIS) cancer samples, 7 invasive breast cancer samples, 7 metastatic breast cancer samples, and 7 normal breast samples) were downloaded from Gene Expression Omnibus (GEO) database. Limma package in R software was applied to identify specific differentially expressed miRNAs of different subtypes of breast cancer. MicroRNA.org database source was used to predict the target genes of the identified differentially expressed miRNAs. We integrated the target genes and their interacted genes (predicted by STRING) into DAVID to perform the GO function and KEGG pathway analyses., Results: Compared to the normal control, a total of 21, 47, and 107 differentially expressed miRNAs were screened in DCIS, invasive and metastatic breast cancer, respectively. Specific differentially expressed miRNAs of the three subtypes were identified, including hsa-miR-99a and hsa-miR-151-3p for DCIS breast cancer, hsa-miR-145 and hsa-miR-210 for invasive breast cancer, and has-miR-205 and has-miR-361-5p metastatic breast cancer. Furthermore, 220, 43, 446, 307, 587 and 328 interaction pairs of the specific miRNA targets were predicted. Multiple GO functions and KEGG pathways were enriched with the miRNA targets and their interacted genes., Conclusions: We screened the most representative miRNAs of the three different subtypes of breast cancer, which may act as the putative markers in the diagnosis of different subtypes of breast cancer.

Objective: Treatments with sequential therapy (SEQ) or bismuth quadruple (QUAD) therapy have been proposed as empirical firstline regimens for Helicobacter pylori. We compared the efficacy and tolerability of 10 day SEQ with 10 day modified QUAD as both firstline and secondline treatments for H pylori in a randomised crossover study., Design: H pylori positive and treatment naïve patients were randomly assigned to receive either 10 day SEQ (esomeprazole for 10 days, amoxicillin for an initial 5 days, followed by clarithromycin and metronidazole for a subsequent 5 days) or modified QUAD (esomeprazole, bismuth subcitrate, tetracycline and metronidazole). H pylori eradication was confirmed by urea breath test at 8 weeks. Patients who failed the initial assigned treatment were crossed over to receive the alternate regimen. The primary outcome was eradication rates of firstline treatment by intention to treat (ITT) and per protocol (PP) analyses., Results: 357 patients were randomised to receive either SEQ or QUAD. The PP eradication rates of the SEQ and QUAD groups were 95.2% and 98.8%, respectively (p=0.10). Based on ITT analysis, the corresponding eradication rates were 89.4% and 92.7%, respectively (p=0.36). Eight (4.8%) patients in the SEQ and two (1.2%) patients in the QUAD who failed the firstline treatment were crossed over to the alternate regimen with 100% retreatment success. The overall incidence of adverse events was higher in the QUAD (16.7%) than in the SEQ (8.1%; p=0.032) group., Conclusions: Ten day sequential and modified bismuth quadruple therapies are both highly effective as empirical firstline therapies for H pylori in Chinese patients., Clinicaltrialsgov: NCT 01760824., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: The relationship between lipids and coronary artery disease has been well established. However, this is not the case between lipids and heart failure. Ironically, high lipid levels are associated with better outcomes in heart failure, but the mechanisms underlying the phenomenon are not fully understood. This study was performed to test the hypothesis that reduced intestinal lipid absorption due to venous congestion may lead to low lipid levels., Methods: We collected data of clinical characteristics, echocardiograph, and lipid profile in 442 unselected patients with congestive heart failure. Correlations between lipid levels [including total cholesterol (TCL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)] and right ventricle end diastolic diameter (RVEDD), left ventricle end diastolic diameter (LVEDD), right atrium diameter (RA), left atrium diameter (LA), or left ventricle ejection fraction (LVEF) were analyzed using Pearson correlation and partial correlation. RVEDD, LVEDD, RA, and LA were indexed to the body surface area., Results: There was a significantly inverse correlation between TCL levels and RVEDD (r = -0.34, P < 0.001) and RA (r = -0.36, P < 0.001). Other lipids such as LDL-C, HDL-C, and TG had a similar inverse correlation with RVEDD and RA. All these correlations remained unchanged after adjusting for age, gender, smoking status, physical activity levels, comorbidities, and medication use., Conclusions: Lipid levels were inversely correlated to RVEDD in patients with congestive heart failure; however, because this was an observational study, further investigation is needed to verify our results as well as identify a causal relationship, if any.

Objective: One of the major concerns regarding the preclose technique is its influence on the diameter of the accessed common femoral artery (CFA). The aim of our study was to evaluate the CFA diameter change after percutaneous endovascular aortic repair (PEVAR) with the use of the preclose technique., Methods: From February 2012 to September 2013, 192 patients who underwent PEVAR with the preclose technique were reviewed. The patients were followed postoperatively with computed tomographic angiography 1, 6, and 12 months after PEVAR, and only those with complete computed tomography studies were included. For each access site, the inner diameter (ID) and outer diameter (OD) of the CFA were measured, and the diameters at various time periods were compared. In addition, the patient cohort was divided into four subgroups according to two parameters: the sheath size (12-16F and 18-24F) and the number of closure devices used for the preclose technique (two devices, more than two devices). The differences in diameter change between the subgroups were analyzed. The significance of the diameter change and the influences of the two parameters were analyzed statistically with the use of the paired t-test, one-way analysis of variance, and two-way analysis of variance., Results: Fifty-eight patients fulfilled the study criteria. No significant influence on the ID of the accessed CFAs was observed at baseline and 1, 6, and 12 months (9.0 ± 1.75 mm, 9.1 ± 1.70 mm, 8.9 ± 1.72 mm, and 9.0 ± 1.68 mm, respectively). By contrast, a significant increase in initial OD occurred 1 month after PEVAR but gradually decreased in size in the following 11 months (13.0 ± 2.37 mm, 16.4 ± 3.44 mm, 14.2 ± 3.06 mm, and 13.5 ± 2.42 mm, respectively). Both the sheath size and the number of closure devices significantly affected the OD change (P < .001 and P = .037, respectively). The effect produced by the number of closure devices extended to 6 months after PEVAR, but the effect of the sheath size ceased before that time., Conclusions: This study demonstrates that PEVAR with the use of the preclose technique does not influence the ID of the accessed CFA, whereas the OD changes gradually over 1 year. These results may indicate that future endovascular interventions can be performed with the use of the same access without the risk of vascular narrowing., (Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Background/purpose: After community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was identified, new community-onset, healthcare-associated MRSA (HA-MRSA-CO) infections have been noticed as MRSA infection in patients with community-onset infection who have underlying conditions resulting in frequent exposure to the healthcare system. However, previous studies have not thoroughly investigated whether HA-MRSA-CO has characteristics resembling those of CA-MRSA or hospital-onset, healthcare-associated MRSA (HA-MRSA-HO) infection., Methods: A multicenter, retrospective study was conducted to analyze the clinical and microbiological data of patients with clinical isolates of MRSA from nine hospitals in Taiwan., Results: In total, 203 patients with MRSA isolates, including 27 patients with CA-MRSA (13.3%), 59 with HA-MRSA-CO (29.1%), and 117 with HA-MRSA-HO (57.6%), were studied. Compared to HA-MRSA-HO isolates, the CA-MRSA and HA-MRSA-CO isolates were associated with a higher proportion of skin and soft tissue infections (81.8% and 65.3% vs. 40.5%, p=0.001 and p=0.002) as well as lesser rate of resistance to ciprofloxacin (33.3% and 50.9% vs. 74.4%, p<0.001 and p=0.002), gentamicin (44.4% and 64.4% vs. 84.6%, p<0.001 and p=0.002), and trimethoprim/sulfamethoxazole (33.3% and 42.4% vs. 58.1%, p=0.02 and p=0.048), and a lower 30-day all-cause mortality rate (7.4% and 0% vs. 20.9%, p<0.001). Most of the CA-MRSA isolates were classified as staphylococcal cassette chromosome mec (SCCmec) type VT (11/27, 40.7%), whereas most HA-MRSA-HO isolates were classified as SCCmec type III (66/117, 56.4%)., Conclusion: The CA-MRSA, HA-MRSA-CO, and HA-MRSA-HO clinical isolates significantly differed in their clinical presentations and molecular characteristics., (Copyright © 2012. Published by Elsevier B.V.)

Objectives: The benefits of narrow band imaging (NBI) on enhancing colorectal adenoma detection remain questionable. We tested whether the new generation of NBI (190-NBI), which is twice as bright as the previous version, would improve adenoma detection when compared with high-definition white light (HD-WL) colonoscopy., Methods: It was a randomized controlled trial with tandem colonoscopy. We recruited patients who underwent colonoscopy for symptoms, screening, or surveillance. Patients were randomized for the use of either 190-NBI or HD-WL on withdrawal. Tandem colonoscopy was performed by using the same assigned colonoscope and withdrawal method. Lesions detected on first-pass and second-pass examination were used for adenoma detection and miss rates, respectively. The primary outcomes were adenoma and polyp detection rates., Results: A total of 360 patients were randomized to undergo either 190-NBI or HD-WL colonoscopy. Both the adenoma and polyp detection rates were significantly higher in the 190-NBI group compared with the HD-WL group (adenoma: 48.3% vs. 34.4%, P=0.01; polyps: 61.1% vs. 48.3%, P=0.02). The mean number of polyps detected per patient was higher in the 190-NBI group (1.49% vs. 1.13, P=0.07). There was no significant difference in the adenoma miss rates between the two groups (21.8% vs. 21.2%). Multivariate analysis showed that the use of 190-NBI (odds ratio (OR) 1.85; 95% confidence interval (CI) 1.10-3.12), withdrawal time (OR 1.29; CI 1.19-1.38), patient's age (OR 1.04; CI 1.01-1.06), and male gender (OR 2.38; CI 1.42-3.99) were associated with adenoma detection., Conclusions: 190-NBI colonoscopy was superior to the conventional HD-WL in detecting colorectal adenomas or polyps, but there was no significant difference in adenoma miss rates.

This study investigates the helical secondary flows in the aortic arch using finite element analysis. The relationship between helical flow and the configuration of the aorta in patients of whose three-dimensional images constructed from computed tomography scans was examined. A finite element model of the pressurized root, arch, and supra-aortic vessels was developed to simulate the pattern of helical secondary flows. Calculations indicate that most of the helical secondary flow was formed in the ascending aorta. Angle α between the zero reference point and the aortic ostium (correlation coefficient (r) = -0.851, P = 0.001), the dispersion index of the cross section of the ascending (r = 0.683, P = 0.021) and descending aorta (r = 0.732, P = 0.010), all correlated closely with the presence of helical flow (P < 0.05). Stepwise multiple linear regression analysis confirmed angel α to be independently associated with the helical flow pattern in therein (standardized coefficients = -0.721, P = 0.023). The presence of helical fluid motion based on the atherosclerotic risks of patients, including those associated with diabetes, hypertension, hyperlipidemia, or renal insufficiency, was also evaluated. Numerical simulation of the flow patterns in aortas incorporating the atherosclerotic risks may better explain the mechanism of formation of helical flows and provide insight into causative factors that underlie them.

Different types of ketorolac ester prodrugs incorporating tert-butyl (KT), benzyl (KB), heptyl (KH), and diketorolac heptyl (DKH) promoieties were synthesized for the comparison of percutaneous penetration. The prodrugs were characterized according to their melting point, capacity factor, lipophilicity, solubility in 30% ethanol/buffer, enzymatic hydrolysis, in vitro skin permeation, hair follicle accumulation, and in vivo skin tolerance. Interactions between the prodrugs and esterases were predicted by molecular docking. Both equimolar suspensions and saturated solutions in 30% ethanol/pH 7.4 buffer were employed as the applied dose. All of the prodrugs exhibited a lower melting point than ketorolac. The lipophilicity increased in the following order: ketorolac < KT < KB < KH < DKH. The prodrugs were rapidly hydrolyzed to the parent drug in esterase medium, skin homogenate, and plasma, with KT and KB exhibiting higher degradation rates. KT exhibited the highest skin permeation, followed by KB. The flux of KT and KB exceeded that of ketorolac by 2.5-fold and twofold, respectively. KH and DKH did not improve ketorolac permeation but exhibited a sustained release behavior. KT and KH revealed selective absorption into follicles and a threefold greater follicular uptake compared with ketorolac. KB, KH, and DKH slightly but significantly increased transepidermal water loss (TEWL) after consecutive administration for 7 days, whereas ketorolac and KT exhibited no influence on TEWL. According to the experimental results, it can be concluded that an optimal balance between lipophilicity and aqueous solubility is important in the design of a successful prodrug. The acceptable skin tolerance for safe application is also an important consideration., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)

Introduction: Rapidly growing mycobacteria (RGM) can cause a broad spectrum of both community and healthcare-associated infections in humans. The aim of this study was to report the clinical management and outcomes of successive patients following cesarean delivery with healthcare-associated surgical site infections (SSIs) caused by RGM., Methodology: Patients who were admitted to Chung Shan Medical University Hospital, Taichung, Taiwan, between September 2006 and July 2008, and who developed SSIs following cesarean delivery at an obstetrics hospital and were then referred to our hospital, were enrolled. Demographic characteristics of the patients and clinical isolates were obtained retrospectively and an environmental investigation was performed. PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of the hsp65gene and pulsed-field gel electrophoresis (PFGE) of large genomic DNA restriction fragments were applied to differentiate Mycobacterium species., Results: Seventeen patients were diagnosed with RGM infections by microbiology and/or histopathology. Mycobacterial isolates by PCR-RFLP analysis from 15 patients revealed Mycobacterium abscessus (M. abscessus) and M. lentiflavum. Most of the patients received surgical debridement and combination antimicrobial therapy and were eventually cured., Conclusions: Our study demonstrates the potential that RGM infections have in causing healthcare-associated SSIs. Surgery plus prolonged combination antimicrobial therapy seemed to be an effective option for the management of M. abscessus infections.

The current study aimed to investigate the rejection and survival time of grafted skin, and the changes of Treg cells, interleukin 10 (IL-10) and transforming growth factor-β (TGF-β) in peripheral blood following skin transplantation with recombinant human interleukin-10 (rhIL-10) or cyclosporin A (CsA), as well as the role of IL-10 in immunological rejection mechanisms. A total of 36 rabbits were divided into two groups. The skin of a donor rabbit was transplanted onto the back of one receptor rabbit. Receptors were randomly divided into six groups, including rhIL-10 low-dose (5 µg/kg/d), rhIL-10 high-dose (10 µg/kg/d), CsA low-dose (5 mg/kg/d), CsA high-dose (10 mg/kg/d), rhIL-10 (5 µg/kg/d) and CsA (5 mg/kg/d) and negative control normal saline (NS; 1 ml/d). All groups received intramuscular drug injection for ten days, beginning one day prior to skin transplantation surgery. Following transplantation, each rabbit's peripheral blood was collected at different times. The changes of CD4+CD25+ regulatory T cells, IL-10 and TGF-β were determined by flow cytometry and enzyme-linked immunosorbent assay. When compared with the control group, the rejection and survival times of the experimental groups were longer following skin graft. Compared with the two CsA groups and the control group, the proportion of CD4+CD25+ regulatory T cells of rhIL-10 groups was significantly upregulated on the 4th and 7th days following surgery. However, TGF-β levels were not significantly different. Data suggested that the concentration of IL-10 was positively correlated with the proportion of CD4+CD25+ regulatory T cells. In addition, IL-10 may delay the rejection time of rabbit skin transplantation and prolong the survival time. Thus, the role of IL-10 in inhibited allograft rejection may be associated with CD4+CD25+ regulatory T cells and IL-10, and may be independent of TGF-β.

Age-dependent memory impairment is known to occur in several organisms, including Drosophila, mouse and human. However, the fundamental cellular mechanisms that underlie these impairments are still poorly understood, effectively hampering the development of pharmacological strategies to treat the condition. Polyamines are among the substances found to decrease with age in the human brain. We found that levels of polyamines (spermidine, putrescine) decreased in aging fruit flies, concomitant with declining memory abilities. Simple spermidine feeding not only restored juvenile polyamine levels, but also suppressed age-induced memory impairment. Ornithine decarboxylase-1, the rate-limiting enzyme for de novo polyamine synthesis, also protected olfactory memories in aged flies when expressed specifically in Kenyon cells, which are crucial for olfactory memory formation. Spermidine-fed flies showed enhanced autophagy (a form of cellular self-digestion), and genetic deficits in the autophagic machinery prevented spermidine-mediated rescue of memory impairments. Our findings indicate that autophagy is critical for suppression of memory impairments by spermidine and that polyamines, which are endogenously present, are candidates for pharmacological intervention.

Two new dihydrothiophene-condensed chromones and a new natural chromone, namely oxalicumones A-C (1-3), respectively, were isolated from a culture broth of a marine-derived fungus, Penicillium oxalicum. The structures of 1-3 and acetylated derivatives of 1 (4-7) were elucidated on the basis of spectroscopic methods and chemical reactions. The absolute configuration of 1 and 2 were established by using the modified Mosher ester method and circular dichroism data of an in situ formed [Rh2(OCOCF3)4] and [Mo2(OAc)4] complex. (R)-MTPA ester of 1 showed cytotoxicity against A375, SW-620, and HeLa carcinoma cell lines with IC50 values of 8.9, 7.8, and 18.4 µM, respectively. Compound 1 displayed cytotoxicity against A375 and SW-620 cell lines with IC50 values of 11.7 and 22.6 µM, respectively. The structure-biological activity relationship of 1 was discussed., (Georg Thieme Verlag KG Stuttgart · New York.)

Diphenidol has been shown to block voltage-gated Na(+) channels, which are associated with specific types of pain. Here, we evaluated the effects of diphenidol on chronic constriction injury (CCI)-evoked allodynia and expression of tumor necrosis factor-α (TNF-α). A peripheral nerve injury was elicited in rats by placing four loosely constrictive ligatures around the sciatic nerve. After intraperitoneal injection of diphenidol, rats were tested for evidence of mechanical allodynia prior to surgery, and on postoperative days 3, 6, 7, 11, 13 and 14. We showed that CCI rats received diphenidol caused dose-dependent increases in mechanical withdrawal threshold. Both diphenidol 2 and 10 μmol/kg groups, but not 0.4 μmol/kg diphenidol, displayed lower TNF-α level in the sciatic nerve than the CCI group (P<0.05) on day 7 after CCI. Our results support the conclusion that systemic diphenidol produced a dose-related inhibition of mechanical allodynia following chronic constriction injury of the sciatic nerve. This antiallodynic effect is related to the decrease of TNF-α expression in the sciatic nerve of CCI rats., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes, public health decision making, and primary prevention synthesis. Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies. Biomarkers are generally classified into three groups: biomarkers of exposure, effect, and susceptibility.The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurological disorders, such as brain damage, mental retardation, behavioral problems, nerve damage, and possibly Alzheimer's disease, Parkinsons disease, and schizophrenia. This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.

Background: Prenatal lead and cadmium exposure will not only influence the mother' organ systems, but also will provide an environment that may influence the fetus and neonate in a harmful way.In the present study, we detected the blood lead levels (BLLS) and cadmium levels for the duration of pregnancy and 6-12 weeks after delivery and to analyze the influencing factors of BLLs in healthy pregnant women., Methods: A cohort study survey was carried out. We recruited 174 healthy pregnant women without pregnancy or obstetric complications or abnormal pregnancy outcomes as the gravida group, and 120 healthy non-pregnant women as the control group., Results: The lead concentrations in the three pregnancy trimesters and in the postpartum period were: (5.98 ± 2.43), (5.54 ± 2.01), (5.59 ± 1.97), and (6.76 ± 1.74) µg/dl; and (6.75 ± 2.13) µg/dl in the control group. The cadmium concentrations in the three pregnancy trimesters and postpartum period were 1.61 ± 0.45, 1.63 ± 0.46, 1.64 ± 0.49, and 1.67 ± 0.57. We found that the BLLs in the gravida group were lower than in the control group during all three trimesters. Occupations, supplement nutritional elements (dietary supplements and nutritional (food) elements), and the time of house painting could affect BLLs in pregnant women. Lead-related occupations, using cosmetics, and living in a house painted more recently than one year previously are risk factors of high BLLs among pregnant women, while calcium, iron, zinc, and milk supplements are protective factors., Conclusions: These findings may help people, especially pregnant women, to reduce lead exposure via supplements of calcium, iron, zinc, and milk or avoiding contacting risk factors.

Background: Self-expandable metallic stents (SEMSs) are effective in the palliation of malignant airway obstruction. Tumor ingrowth, however, frequently occurs because of a shortage of effective local therapy. Additionally, SEMSs are frequently associated with problems of fracture, migration, and difficult removals. Our goal was to develop a novel bioabsorbable stent with cisplatin elution to circumvent such problems., Methods: Biodegradable stents made of polycaprolactone were fabricated by a laboratory-made, microinjection molding machine. In vitro mechanical strength of the stents was compared with the strength of Ultraflex SEMSs. Polylactide-polyglycolide copolymer and cisplatin were coated onto the surfaces of the stents. Elution method and high-performance liquid chromatography (HPLC) analysis were used to examine the in vitro cisplatin release characteristics. In vivo, the stents were surgically implanted into the cervical trachea of 15 New Zealand white rabbits. Bronchoscopic examination was performed weekly (1 to approximately 5 weeks) before killing. Cisplatin concentrations in trachea, lung, and blood were analyzed by HPLC. Histologic examination was also performed., Results: The biodegradable stent exhibited mechanical strength comparable to the strength of Ultraflex SEMSs and provided a steady release of cisplatin for >4 weeks in vitro. The in vivo study showed sustained cisplatin levels in rabbit trachea for >5 weeks with a minimum drug level in blood. Histologic examination showed an intact ciliated epithelium and marked leukocyte infiltration in the submucosa of the stented area., Conclusions: Our study demonstrated that the biodegradable stents provided physical properties comparable to the properties of SEMSs and a sustained release of cisplatin for >5 weeks, which showed great potential in the treatment of malignant airway obstruction.

Objective: To investigate the blood lead levels (BLLs) in the duration of pregnancy and 6-12 weeks after delivery, and analyze the influencing factors of BLLs in healthy pregnant women., Methods: Pregnant women were recruited from September 2009 to February 2010 at the prenatal clinic in Nanjing Maternity and Child Health Care Hospital. Altogether 174 healthy pregnant women without pregnant or obstetric complications or abnormal pregnancy outcomes were enrolled as the gravida group, and 120 healthy non-pregnant women as the control group. BLLs during pregnancy were determined by flame atomic absorption spectroscopy., Results: BLLs in all the three pregnancy trimesters and postpartum were 59.8±24.3, 55.4±20.1, 55.9±19.7, and 67.6±17.4 μg/L, respectively, and the mean BLL in control group was 67.5±21.3 μg/L. BLLs during all the three trimesters were lower in the gravida group than in the control group (P=0.043, 0.021, and 0.028). Furthermore, occupations, nutrients supplementation, and time of house/apartment painted were associated with BLLs in pregnant women. Lead-related occupations, cosmetics use, and living in a house painted less than 1 year before are risk factors of high BLLs among pregnant women, while calcium, iron, zinc, and milk supplements are protective factors., Conclusion: Supplementing calcium, iron, zinc, and milk, or avoiding contact with risk factors may help people, especially pregnant women, to reduce lead exposure.

Background/purpose: Urinary tract infection (UTI) is the most common type of infectious complication among kidney transplant patients. However, the antibiotic susceptibility of causative microorganisms and risk factors for concomitant bacteremia and recurrent infection are rarely discussed., Methods: This was a retrospective cohort review of kidney transplant recipients who had received follow-up in the past 10 years at the Chung-Shan Medical University (Taichung, Taiwan). Only community-acquired and symptomatic UTIs were included in this study., Results: During the 53 ± 22 months of follow-up, 99 patients developed 167 episodes of UTI. Forty-two (25%) episodes had concomitant bacteremia. Escherichia coli was the most common causative microorganism, and strains with resistance to multiple commonly used empirical antibiotics began to emerge. The independent risk factors for UTI with concomitant bacteremia in multivariate analysis were immunosuppression with tacrolimus (adjusted odds ratio [AOR] 3.17; 95% confidence interval [CI] 1.29-7.75; P = 0.011) and baseline serum creatinine level >1.3 mg/dL before first UTI (AOR 2.55; 95% CI 1.02-6.36; P = 0.045). However, there were no factors that were significantly associated with recurrent infection., Conclusion: From this study, we found that E coli tends to have resistance to commonly used empirical antibiotics in this modern era and that patients who use the immunosuppressant tacrolimus and have baseline serum creatinine level >1.3 mg/dL before their first UTI have a tendency to suffer from concomitant bacteremia and even sepsis., (Copyright © 2012. Published by Elsevier B.V.)

Background: Acute detoxification may lead to withdrawal syndrome. The syndrome is sufficiently aversive in those who are morphine-dependents and thus it hinders abstinence. The opioids are most often used clinically to lighten this syndrome. Here, we evaluated the effects of tricyclic antidepressants (TCAs) in treating physical dependence to opioids upon acute detoxification in mice., Materials and Methods: Adult NRL mice were rendered physically dependent on morphine by increasing daily doses of subcutaneous morphine for 3 days and precipitated withdrawal jumping by subcutaneous naloxone on Day 4. The mice were then assigned to receive intramuscular saline or one of the five TCAs 1 hour prior to creating naloxone-precipitated withdrawal. The withdrawal jumping frequency in 30 minutes was counted after naloxone-precipitated withdrawal., Results: Our results (the newest findings) based on the equimolar dose (30 μmol/kg), showed that the severity of physical dependence on morphine could be attenuated with less intramuscular TCAs [percent maximal possible effect (MPE) < 50). Amoxapine, protriptyline, amitriptyline, clomipramine, and trimipramine produced a mean percent MPE (43, 18, 37, 45, and 36, respectively); amoxapine, protriptyline, amitriptyline, and clomipramine, also produced a dose-related effect on attenuating the severity of morphine dependence, but not trimipramine. A higher dose had a stronger effect., Conclusion: Amoxapine, trimipramine, protriptyline, amitriptyline, and clomipramine could have a lightening effect on physical dependence on morphine., (Copyright © 2013. Published by Elsevier B.V.)

Objective: To evaluate levels of lead (Pb) and cadmium (Cd) in the breast milk in the second postpartum month, to investigate the relationship between Pb/Cd levels in breast milk and some sociodemographic parameters, and to explore whether these levels affect the infants' physical status or the mothers' psychological status (postpartum depression)., Methods: A cross-sectional study was conducted between November 2009 and December 2010. Altogether 170 healthy mothers were enrolled from Nanjing Maternity and Child Health Care Hospital. The inclusion criteria were: voluntary to participate in this study, healthy, with no chronic disease, breastfeeding in the second postpartum month, living in a suburban but not non-industrial area of Nanjing, and not occupationally exposed to toxic metals. All the mothers completed a questionnaire and were evaluated based on the Edinburgh Postpartum Depression Scale (EPDS) to identify the risk of postpartum depression. Pb and Cd levels in breast milk were determined by inductively coupled plasma mass spectroscopy. The infants of these mothers were examined for their z scores of weight for age, length for age, head circumference for age, and body mass index for age., Results: The median breast milk levels of Pb and Cd were 40.6 μg/L and 0.67 μg/L, respectively. In 164 (96.5%) of the 170 samples, Pb levels were higher than the limit reported by the World Health Organization (> 5 μg/L). Breast milk Cd level was > 1 μg/L in 54 (31.8%) mothers. The mothers with a history of anemia had a higher breast milk Pb level than those without a history of anemia (41.1 μg/L vs. 37.9 μg/L, P = 0.050). The median breast milk Cd level in those who were active and passive smokers during pregnancy was significantly higher than that in non-smokers (0.88 μg/L vs. 0.00 μg/L, P = 0.025). The breast milk Cd level in the mothers not taking iron and vitamin supplements for 2 months postpartum was higher than in those taking the supplements (iron supplement: 0.74 μg/L vs. 0.00 μg/L, P = 0.025; vitamin supplement: 0.78 μg/L vs. 0.00 μg/L, P = 0.005). Breast milk Cd level at the second postpartum month was negatively correlated with the z scores of head circumference (r = - 0.248, P = 0.042) and weight for age at birth (r =- 0.241, P = 0.024) in girls. No correlation was found between the breast milk Pb/Cd levels and the EPDS scores., Conclusion: Considering the high levels of Pb and Cd in breast milk in this study, breast milk monitoring programs are necessary.