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Fibrolamellar carcinoma is a rare primary hepatocellular malignancy arising in noncirrhotic livers of young individuals. Patients commonly present with a large solitary liver mass and nonspecific symptoms. Characteristic histologic features include large polygonal cells with oncocytic cytoplasm and prominent nucleoli separated into trabeculae and cords by dense parallel bands of collagen. Important differential diagnoses include classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma, which may be distinguished by a judicious panel of immunohistochemical studies, including cytokeratin 7, CD68, and hepatocyte paraffin 1 (HepPar-1). In addition, fibrolamellar carcinomas are characterized by activation of protein kinase A. Prognosis of fibrolamellar carcinoma is similar to classical hepatocellular carcinoma occurring in the absence of liver cirrhosis and is strongly correlated with tumor resectability. Other treatment options include liver transplant, chemotherapy, and hepatic artery embolization. In this article, we review the clinical features, gross and microscopic pathology, molecular genetics, differential diagnosis, treatment, and prognosis of this rare and interesting tumor. [ABSTRACT FROM AUTHOR]

Background Preclinical studies involving animal models are essential for understanding the underlying mechanisms of diabetic neuropathic pain. Methods Rats were divided into four groups: two controls and two experimental. Diabetes mellitus was induced by streptozotocin (STZ) injection in two experimental groups. The first group involved one shamoperation. The second group involved one latex tube encircling the sciatic nerve. The vehicle-injection rats were used as two corresponding control groups: sham operation and encircled nerves. By the third week, STZ-injected rats with encircled nerves were further divided into three subgroups: one involving continuing observation and the other two involving decompression (removal of the latex tube) at different time points (third week and fifth week). Weight and blood glucose were monitored, and behavioral analysis, includingpawwithdrawal threshold(PWT) and latency, was performed every week during the experimental period (7 weeks). Results Hyperglycemia was induced in all STZ-injected rats. A significant increase in weight was observed in the control groups when compared with the experimental groups. By the third week, more STZ-injected rats with encircled nerves developed mechanical allodynia than those without (P < 0.05), while no significant differencewas noted (P > 0.05) on the incidence of thermal hyperalgesia. Mechanical allodynia, but not thermal hyperalgesia, could be ameliorated by the removal of the latex tube at an early stage (third week). Conclusion With the combined use of a latex tube and STZ injection, a stable rat model of painful diabetic peripheral neuropathy (DPN) manifesting both thermal hyperalgesia and mechanical allodynia has been established. [ABSTRACT FROM AUTHOR]

In diabetic patients, left ventricular (LV) remodeling is highly prevalent; however, little is known about the impact of diabetes on right ventricular (RV) structure and function. We recently found that overexpression of angiotensin (ANG)-converting enzyme 2 (ACE2), which metabolizes ANG-II to ANG-(1-7) and ANG-I to ANG-(1-9), may improve LV remodeling in diabetic cardiomyopathy (DCM). Here, we aimed to assess whether LV remodeling and dysfunction are paralleled by RV alterations and the effects of ANG-(1-7) on RV remodeling in DCM. After 12 wk of diabetes induced by a single intraperitoneal injection of streptozotocin, rats were treated with saline, ANG-(1-7), perindopril, ANG-(1-7) plus perindopril, ANG-(1-7) plus Mas receptor antagonist A779, or ANG-(1-7) plus ANG-II type 2 receptor antagonist PD123319 for 4 wk. RV remodeling in diabetic rats was indicated by fibrosis of the RV free wall in the absence of hypertrophy and apoptosis. Treatment with ANG-(1-7) prevented diabetes-induced RV fibrosis and dysfunction. ANG-(1-7) (800 ng·kg-1·min-1) was superior to perindopril in improving RV fibrosis. The major mechanisms involved a complex interaction of ANG-II type 2 and Mas receptors for subsequent downregulation of ACE expression and activity and ANG-II type 1 receptor expression, as well as upregulation of ACE2 expression and activity and the expression of ANG-II type 2 receptor and sarco(endo)plasmic reticulum Ca2+-ATPase. Thus RV fibrosis and dysfunction plays a central role in DCM, and ANG-(1-7) mitigates diabetes-induced RV alterations. [ABSTRACT FROM AUTHOR]

Background/Aims DA-9701 significantly improved gastric accommodation by increasing the postprandial gastric volume. In this study, we investigated how DA-9701 affects the rat gastric fundus relaxation. Methods Gastric fundus muscle strips (9 longitudinal and 7 circular muscles) were obtained from rats. Electrical field stimulation (EFS) was performed at various frequencies (1, 5, 10 and 20 Hz) and train durations (1, 5, 10 and 20 seconds) to select optimal condition for experiments. Isometric force measurements were performed in response to EFS. Peak and nadir were observed during the first 1 minute after initiation of EFS in control state and after sequential addition of atropine (1 µM), DA-9701 (0.5, 5, 25 and 50 µg), N-nitro-L-arginine (L-NNA, 100 µM), MRS2500 (1 µM) and tetrodotoxin (TTX, 1 µM) to the organ bath. Results The optimal frequency and duration of EFS to evoke nerve-mediated relaxation was determined as 5 Hz for 10 seconds. Addition of L-NNA in the presence of atropine and DA-9701 (50 µg) decreased nadir by inhibiting relaxation from -0.054 ± 0.021 g to -0.022 ± 0.015 g (P = 0.026) in longitudinal muscles. However, subsequent application of MRS2500 in the presence of atropine, DA-9701 (50 µg) and L-NNA did not affect nadir. In circular muscles, subsequent addition of L-NNA and MRS2500 in the presence of atropine and DA-9701 (50 µg) did not show significant change of nadir. Conclusions Our data suggest that the effect of DA-9701 on the rat gastric fundus relaxation is mainly mediated by nitrergic rather than purinergic pathway. [ABSTRACT FROM AUTHOR]

Although the accepted standard of care during the induction treatment of active lupus nephritis (LN) has been cyclophosphamide (CYC), recent trials suggest that calcineurin inhibitors (CNIs), which include cyclosporine A (CsA) and tacrolimus (TAC), may be just as, or even more, effective and less toxic than CYC. A systematic review and meta-analysis were performed to evaluate the clinical effects of CNIs on active LN compared with those of CYC. In the present study, clinical trials that compared CNIs with CYC in the induction therapy of active LN were searched in the Cochrane Library, Ovid and PubMed databases. The clinical data on renal remission and side-effects were collected and analyzed. The relative risk (RR) and 95% confidence intervals (CIs) were calculated. As a result, six controlled trials involving 265 patients were included in the meta-analysis, four of which compared TAC (treatment group) with CYC (control group), and the other two compared CsA (treatment group) with CYC (control group). CNIs were superior to CYC for higher complete remission (RR=1.56, 95% CI 1.14-2.15, Z=2.74, P=0.006) and better overall response/total remission (RR=1.23, 95% CI 1.07-1.42, Z=2.87, P=0.004) and had fewer side-effects. Among the CNIs, TAC demonstrated more favorable results than CsA. Therefore, it was concluded that CNIs may be a reasonable alternative to CYC in the induction treatment of active LN. However, large-scale, multicenter, well-designed clinical trials should be adopted to further confirm this conclusion. [ABSTRACT FROM AUTHOR]

Pemetrexed (PEM), a multi-targeted antifolate, has promising clinical activity in non-squamous non-small cell lung cancer. However, the majority of patients eventually acquire resistance to PEM. To evaluate the resistant mechanisms, the A549 lung adenocarcinoma cell line was exposed to stepwise increasing PEM concentrations of 1.6, 6.4 and 16 µM to establish three PEM-resistant lung cancer cell lines, A549/PEM-1.6, -6.4 and -16. Growth inhibition was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assay. Expression of the genes encoding thymidylate synthase (TS), reduced folate carrier (RFC) and folypoly-γ-glutamate synthetase (FPGS) were analyzed by quantitative real-time reverse transcription polymerase chain reaction. The three A549 cell lines showed more resistance to PEM (3.7-, 17.3- and38.0-fold, respectively) compared with that of the parental cell line, which also showed cross-resistance to cisplatin, but not to docetaxel, vinorelbine and 5-Fluorouracil (5-FU). TS gene expression was significantly increased in three PEM-resistant cells, relative to that of the parental cells, in a PEM dose-dependent manner. Knockdown of TS expression with siRNA enhanced the cytotoxicity of PEM in A549/PEM-16 cells. By contrast, the levels of RFC and FPGS gene expression in A549/PEM-1.6 and -6.4 cells were significantly decreased, whereas the levels of the two genes were restored in A549/PEM-16 cells. In summary, PEM-resistant A549 cells remained sensitive to docetaxel, vinorelbine and 5-FU. TS expression appeared to be associated with resistance to PEM, which may be a predictive marker for PEM sensitivity in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

The common predisposing risk factors for perioperative stroke include: previous stroke, atrial fibrillation, old age (> 75 years), carotid stenosis, and diabetes mellitus. An endoscopic sinus surgery was performed in a 49-year-old male with chronic paranasal sinusitis and nasal polyps. The vital signs, physical and laboratory examinations, and electrocardiography on admission were within the normal limit. Anesthesia was maintained with nitrous oxide in oxygen and 6% desflurane. The operation and anesthesia were uneventful with the exception of transient intraoperative hypotension. The patient recovered fully from the anesthesia (modified Aldrete score: 10) in the recovery room. However, he developed right arm weakness and dysarthria in the general ward 7 hours after the operation. We report a rare case of multifocal acute cerebral infarctions found on the postoperative magnetic resonance imaging in a noncardiac surgical patient. [ABSTRACT FROM AUTHOR]

Background: Nonampullary sporadic duodenal adenomas (NSDAs) are uncommon mucosal neoplasms with malignant potential. Recently, endoscopic treatment is used for NSDA with increasing frequency. Aims: This study therefore aimed to evaluate the efficacy and safety of endoscopic treatment for NSDA. Methods: A total of 36 NSDAs in 35 consecutive patients were endoscopically eradicated at Samsung Medical Center between October 1994 and May 2011. Data on patient demographics, tumor characteristics, and endoscopic treatment outcomes were obtained and retrospectively analyzed. Results: Of all patients, 19 (52.8 %) were male. The mean age was 56.0 ± 12.2 (SD) years. Of the 36 NSDAs, 23 lesions were removed by endoscopic resection (ER) including endoscopic mucosal resection (EMR, n = 20) and snare polypectomy ( n = 3). In the 23 cases treated with ER, en bloc resection was achieved in 20 (87.0 %). All cases undergoing en bloc resection showed tumor-free resection margins. Thirteen lesions were ablated by argon plasma coagulation (APC). During EMR, bleeding occurred in two cases and perforation occurred in one case. One patient bled during APC. All complications were successfully managed with endoscopic treatment without surgical intervention. During a median follow-up period of 11.4 months (range, 1.8-182.4 months), local recurrence occurred in one patient treated with APC (1/10, 10.0 %). Among patients undergoing ER, no local recurrence occurred but one patient treated with EMR experienced metachronous recurrence. Conclusions: Endoscopic treatment, including EMR, snare polypectomy, and APC, was an effective and safe treatment for NSDA. Further multi-center large prospective studies are warranted to establish appropriate treatment guidelines for NSDA. [ABSTRACT FROM AUTHOR]

The globo-series glycosphingolipids (GSLs) SSEA3, SSEA4, and Globo-H specifically expressed on cancer cells are found to correlate with tumor progression and metastasis, but the functional roles of these GSLs and the key enzyme β1,3-galactosyltransferase V (β3GalT5) that converts Gb4 to SSEA3 remain largely unclear. Here we show that the expression of β3GalT5 significantly correlates with tumor progression and poor survival in patients, and the globo-series GSLs in breast cancer cells form a complex in membrane lipid raft with caveolin-1 (CAV1) and focal adhesion kinase (FAK) which then interact with AKT and receptor-interacting protein kinase (RIP), respectively. Knockdown of β3GalT5 disrupts the complex and induces apoptosis through dissociation of RIP from the complex to interact with the Fas death domain (FADD) and trigger the Fas-dependent pathway. This finding provides a link between SSEA3/SSEA4/Globo-H and the FAK/CAV1/AKT/RIP complex in tumor progression and apoptosis and suggests a direction for the treatment of breast cancer, as demonstrated by the combined use of antibodies against Globo-H and SSEA4. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 55-year-old man who was hospitalized for upper abdominal pain, and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed, which revealed the white blood cell count of 6020 that later developed into gastric wall abscess.

Background: The immunogenomic changes triggered by concurrent chemoradiation therapy (CCRT), a standard neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma (ESCC), are unknown. We aimed to analyze the early immunogenomic changes in ESCC induced by CCRT and to correlate them with clinical outcomes. Methods: We collected biopsy samples from 40 patients with ESCC and the surgical candidates were treated with 5-fluorouracil (5-FU)/Cisplatin and concurrent radiation therapy. Endoscopic biopsy was performed before and after one treatment cycle of 5-FU/Cisplatin and 5 to 18 fractions of radiation. We analyzed immunogenomic changes using paired whole-exome sequencing (n = 29) and paired whole-transcriptome sequencing (WTS, n = 23). Multiplex immunohistochemistry (IHC) was conducted in four representative pair samples. Results: Fourteen out of 23 WTS samples (60.8%) showed increased immune scores after CCRT, as calculated by ESTIMATE. The rate of progression-free survival was higher in patients with increased immune scores compared with the remaining patients (83.1% vs. 57.1%, p = 0.25). Tumor mutation burden and neoantigen load were significantly reduced after CCRT (p < 0.001). We observed no specific correlation with non-synonymous mutations and no changes in the single-nucleotide variant spectrum after CCRT. Post-CCRT samples were enriched in gene sets related to immune signaling pathways, such as interferon gamma signaling and CD28 co-stimulation. Multiplex IHC showed an incremental trend in the proportion of CD4 positive cells in cytokeratin positive region after CCRT. However, CD8, CD20, FOXP1, PD-L1 showed no definitive trend. Proportion of immune cells calculated by CIBERSORT, showed that significant increase in neutrophils after CCRT. Conclusions: We have comprehensively analyzed the early immunogenomic changes induced in ESCC by CCRT and correlated them with clinical outcomes. Our results provide a potential basis for combining immunotherapy with CCRT for the treatment of ESCC. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid (BP), a common autoimmune skin disease, is associated with IgG autoantibodies against the hemidesmosomal proteins, BP180 and BP230. In addition to IgG, IgE has been shown to play a role in the disease. However, the association between disease activity and IgE specific to the NC16A domain of BP180 in blister fluid remains unclear. Our objective was to evaluate the correlation between BP disease activity and BP180 NC16A-specific IgE sera and blister fluid titers, and to analyze changes during treatment. We evaluated the levels of anti-BP180 IgE autoantibodies in the sera and blister fluids of 37 BP patients using an Enzyme-linked immunosorbent assay. We also observed changes in the levels of these antibodies in 2 BP patients at 4 or 5 different time points (day 0 when the patient first visited our hospital, day 5, day 14, day 39 and day 62 for patient 1; day 0, day 4, day 8 and day 17 for patient 2). We also collected extra serum samples from the 2 patients when the disease was controlled (blister disappeared) (day 85, day 104 and day 146 for patient 1 and day 123, day 158 and day 189 for the other patient). IgE anti-BP180 antibodies were detected in the serum of 72.97 % of the patients. There was no correlation between disease activity scores and BP180 NC16A IgE titers in serum ( r = −0.077, p > 0.05) or in blister fluid ( r = 0.262, p > 0.05). The levels of the autoantibody in serum were positively correlated with that in blister fluid ( r = 0.6651, p < 0.001); however, the levels continued to rise despite effective control of the disease in the initial two to 6 weeks of diagnosis. The level of this autoantibody reached a peak on day 39 for patient 1 and on day 17 for patient 2 although the systemic and topical medication of steroid had controlled the disease process effectively. We conclude that levels of anti-BP180 NC16A IgE are higher in the sera than blister fluids. These levels could generally reflect disease severity throughout the course of the disease, but not in the early stages of medication. [ABSTRACT FROM AUTHOR]

Background: The top 3% of frequent attendance in primary care is associated with 15% of all appointments in primary care, a fivefold increase in hospital expenditure, and more mental disorder and functional somatic symptoms compared to normal attendance. Although often temporary if these rates of attendance last more than two years, they may become persistent (persistent frequent or regular attendance). However, there is no long-term study of the economic impact or clinical characteristics of regular attendance in primary care. Cognitive behaviour formulation and treatment (CBT) for regular attendance as a motivated behaviour may offer an understanding of the development, maintenance and treatment of regular attendance in the context of their health problems,cognitive processes and social context.Methods/design: A case control design will compare the clinical characteristics, patterns of health care use and economic costs over the last 10 years of 100 regular attenders (≥30 appointments with general practitioner [GP]over 2 years) with 100 normal attenders (6.22 appointments with GP over 2 years), from purposefully selected primary care practices with differing organisation of care and patient demographics. Qualitative interviews with regular attending patients and practice staff will explore patient barriers, drivers and experiences of consultation,and organisation of care by practices with its challenges. Cognitive behaviour formulation analysed thematically will explore the development, maintenance and therapeutic opportunities for management in regular attenders. The feasibility, acceptability and utility of CBT for regular attendance will be examined.Discussion: The health care costs, clinical needs, patient motivation for consultation and organisation of care for persistent frequent or regular attendance in primary care will be explored to develop training and policies for service providers. CBT for regular attendance will be piloted with a view to developing this approach as part of a multifaceted intervention. [ABSTRACT FROM AUTHOR]

SUMMARY Aims: To investigate the anticerebral ischemic properties of YGY-E (apigenin-7-O-β- d-glucopyranosy l-4′-O-α-L-rhamnopy-ranosid, a flavonoid glycoside extracted from plant phoenix-tail fern), focusing on its effects on neuronal apoptosis. Methods: In vitro YGY-E treatment was examined in primary cultured rat hippocampal neurons subjected to hypoxia-reoxygenation (H-R) injury. In addition, in vivo effects of YGY-E on neuronal apoptosis were measured by Hoechst staining and in situ DNA end labeling (TUNEL). Finally, B cell lymphoma/lewkmia-2 (Bcl-2) level in ischemic rat brain tissue was evaluated with immunohistochemistry and western blot analyses. Results: In vitro YGY-E (50-100 μg/mL) treatment increased the survival rate compared to that of the vehicle-treated group ( P < 0.05 and P < 0.01, respectively). In in vivo experiments, YGY-E (2.5-10 mg/kg) decreased the percentage of apoptotic neurons ( P < 0.01), increased Bcl-2 ( P < 0.01) in ischemic rat brain tissue. These effects were dose dependent. Conclusions: Our findings indicate that YGY-E's neuroprotective effects may be because of its inhibition of neuronal apoptosis by increasing Bcl-2 expression. [ABSTRACT FROM AUTHOR]

Targeting cellular function as a system rather than on the level of the single target significantly increases therapeutic potency. In the present study, we detect the target pathway of salvianolic acid B (SalB) in vivo. Acute myocardial infarction (AMI) was induced in rats followed by the treatment with 10 mg/kg SalB. Hemodynamic detection and pathological stain, 2- dimensional electrophoresis, MALDI-TOF MS/MS, Western blot, pathway identification, apoptosis assay and transmission electron microscope were used to elucidate the effects and mechanism of SalB on cardioprotection. Higher SalB concentration was found in ischemic area compared to no-ischemic area of heart, correlating with improved heart function and histological structure. Thirty-three proteins regulated by SalB in AMI rats were identified by biochemical analysis and were classified as the components of metabolism and apoptosis networks. SalB protected cardiomyocytes from apoptosis, inhibited poly (ADP-ribose) polymerase-1 pathway, and improved the integrity of mitochondrial and nucleus of heart tissue during AMI. Furthermore, the protective effects of SalB against apoptosis were verified in H9c2 cells. Our results provide evidence that SalB regulates multi-targets involved in the apoptosis pathway during AMI and therefore may be a candidate for novel therapeutics of heart diseases. [ABSTRACT FROM AUTHOR]

Background: A nonsurgical intervention, interventional microadhesiolysis, was developed to release adhesions in joints and soft tissues. This paper introduces the procedure and evaluates the efficacy of the intervention for adhesive capsulitis of the shoulder. Methods: Ten patients (five men and five women) with primary adhesive capsulitis of the shoulder were treated at a chronic pain management center in Korea. Three specially made needles are used in interventional microadhesiolysis: the Round, Flexed Round, and Ahn's needles. A Round Needle is inserted on the skin over middle of supraspinatus and advanced under the acromion and acromioclavicular joint (subacromial release). A Flexed Round Needle is inserted two-fingers caudal to the inferior border of the scapular spine and advanced over the capsule sliding on the surface of infraspinatus muscle-tendon fascia. The capsule is released while an assistant simultaneously passively abducts the shoulder to full abduction (posteroinferior capsule release). An Ahn's Needle is inserted on the skin over the lesser tubercle and advanced under the coracoid process sliding on the surface of the subscapularis muscle (subcoracoid release). Results: After the patients underwent interventional microadhesiolysis, the self-rated pain score or severity declined significantly (p < .01), the shoulder range of motion increased significantly (p < .01), and joint effusion in the affected shoulder decreased or disappeared in nine of ten patients on magnetic resonance imaging compared to their initial status. Conclusion: Our findings suggest that interventional microadhesiolysis is effective for managing adhesive capsulitis of the shoulder. [ABSTRACT FROM AUTHOR]

Analyzes the effectiveness of antibiotics with bacterial susceptibility. Characteristics of the patients; Factors that led to orbital cellulitis; Bactericidal action of aminoglycosides; Comparison of the bactericidal actions between penicillins and cephalosporins.

Background: The survival following transarterial chemoembolization (TACE) alone is still low in unresectable hepatocellular carcinoma (HCC) with almost patients developing disease progression after treatment. There is need to investigate additional therapeutic options that would intensify the initial response to TACE. The present study was to retrospectively compare the outcome and evaluate the prognostic factors of stereotactic body radiation therapy (SBRT) alone or as an adjunct to transarterial embolization (TAE) or TACE in the treatment of HCC >5 cm.Methods: From January 2011 to April 2015, 77 patients received SBRT followed by TAE or TACE (TAE/TACE + SBRT group) and 50 patients received SBRT alone (SBRT group). The dose of SBRT was 30-50 Gy which was prescribed in 3-5 fractions. Eligibility criteria were: a longest tumor diameter >5.0 cm and Child-Turcotte-Pugh (CTP) Class A or B. Exclusion criteria included tumor thrombus, lymph node involvement and extrahepatic metastasis.Results: The median follow-up period was 20.5 months. Median tumor size was 8.5 cm (range, 5.1-21.0 cm). Median overall survival (OS) in the TAE/TACE + SBRT group was 42.0 months versus 21.0 months in the SBRT group. The 1-, 3- and 5-year OS was 75.5, 50.8, and 46.9 % in the TAE/TACE + SBRT group and was 62.4, 32.9, and 32.9 % in the SBRT group, respectively (P = 0.047). The 1-, 3- and 5-year distant metastasis-free survival (DMFS) was 66.3, 44.3, and 40.6 % in the TAE/TACE + SBRT group and was 56.8, 26.1, and 17.4 % in the SBRT group, respectively (P = 0.049). The progression-free survival (PFS) and local relapse-free survival (LRFS) were not significantly different between the two groups. In the entire patient population, a biologically effective dose (BED10) ≥100 Gy and an equivalent dose in 2 Gy fractions (EQD2) ≥74 Gy were significant prognostic factors for OS, PFS, LRFS and DMFS.Conclusions: SBRT combined with TAE/TACE may be an effective complementary treatment approach for HCC >5 cm in diameter. BED10 ≥100 Gy and EQD2 ≥74 Gy should receive more attention when the SBRT plan is designed. [ABSTRACT FROM AUTHOR]