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Context:Ganoderma lucidum(Leyss: Fr) Karst. (Polyporaceae) is an oriental medicinal fungus, commonly used in traditional Chinese medicine (TCM) for treating various condition or diseases such as hypertension, hyperglycaemia, hepatitis and cancer. Objective:The current study examines whether triterpenoids and polysaccharide-enrichedG. lucidum(GL) influence antioxidation and hepatoprotective efficacy by suppressing oxidative stress. Materials and methods:Forty-two healthy subjects (22 male and 20 female) were recruited and segregated into two groups as experimental or placebo and requested to intake GL (n = 21) or placebo (n = 21) capsule (225 mg; after lunch or dinner) for six consecutive months andvice versawith one month washout period in between. The anthropometric analysis and biochemical assays, as well as abdominal ultrasonic examination were performed. Results:Consumption of GL substantially improved (p < 0.05) the total antioxidant capacity (TEAC; 79.33–84.04), total thiols and glutathione content (6–8.05) in plasma as well as significant (p < 0.05) enhanced the activities of antioxidant enzymes. Whereas, the levels of thiobarbituric acid reactive substances (TBARS; 3.37–2.47), 8-hydroxy-deoxy-guanosine (8-OH-dG; 15.99–11.98) and hepatic marker enzymes (glutamic-oxaloacetic transaminase; GOT and glutamic-pyruvic transaminase; GPT) were concomitantly reduced (42 and 27%) on treatment with GL. Furthermore, the abdominal ultrasonic examination in GL subjects displayed a notable alteration on hepatic condition by reversing from mild fatty liver condition (initial) to normal condition. Discussion and Conclusion:The outcome of the present intervention demonstrated the antioxidation, anti-aging and hepatoprotective nature of GL by effectively curbing oxidative stress. [ABSTRACT FROM PUBLISHER]

Purpose: To explore the effect of Paeonia lactiflora Pall. extract on depression in rats. Methods: Various doses (150, 300 and 600 mg/kg) of Paeonia lactiflora Pall. extract (PLPE) were orally administered to three groups of rats of 10 each, respectively, suffering from depression for 14 days. Fluoxetine was used as positive control. Tail suspension, forced swimming and monoamine oxidase (MAO) tests were carried out on the rats. Results: A dose-dependent reduction in rat immobility was observed. The effect of PLPE at the highest dose (600 mg/kg) was more potent than that of the reference antidepressant, fluoxetine. PLPE, at a dose = 150 mg/kg significantly inhibited MAO A activity in rat whole brain in a dose-dependent manner (p < 0.01); however, only oral administration of PLPE at a dose of 600 mg/kg produced observable MAO B inhibitory activity in rat brain (p < 0.01). Only fluoxetine showed a tendency to inhibit both MAO A and B activities in animal brain. Neither PLPE nor fluoxetine, at the doses tested, produced significant effects on locomotor activity. Conclusion: The results suggest that Paeonia lactiflora Pall is a potential agent for the treatment of depression in humans. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in differential diagnosis of gastric cancer and gastritis, with histological results as reference standard. Methods: From September 2011 to August 2014, 82 patients (50 males and 32 females; mean age ± SD, 59.5 ± 15.0 years; range 19-91 years) with gastric cancer or gastritis were included in this Ethics Committee-approved prospective study. Conventional ultrasonography (US) and CEUS were applied to distinguish the two lesions, and both qualitative and quantitative features were evaluated. Results: Of the 82 histopathologic-proven lesions, 58 were cancer and 24 were gastritis. For US, the gastric wall stratification was not preserved in about one-third of cancer (21/58, 36.2%) compared with gastritis (0/24, 0%) ( p < 0.001). Blurred, angular, or spiculated serosa margin and increased echogenicity in perigastric fat appeared only in cancer (10/58, 17.2%), and all of them proved to be pathologic T3 or T4 stage. On CEUS, gastric cancer usually manifested as diffused enhancement without comb-teeth-like vessels (parallel curvilinear structures representing arterial branching within the gastric wall) (56/58, 96.6%), while these vessels presented in most gastritis (19/24, 79.2%, p < 0.001). For quantitative analysis, the malignant lesions showed later and lower enhancement ( p < 0.001), and they also had slower speed to reach the peak intensity ( p < 0.001). On CEUS, the absence of comb-teeth-like vessel is most reliable for diagnosing malignancy, and the sensitivity, specificity, and accuracy were 96.5%, 79.2%, and 91.5%, respectively. Conclusions: Our results demonstrated the usefulness and accuracy of US and CEUS in differential diagnosis of gastric cancer and gastritis. CEUS has the potential to make the diagnosis more accurate. [ABSTRACT FROM AUTHOR]

Nucleus pulposus (NP) has been suggested to trigger an autoimmune response if exposed to the immune system, which plays a key role in neuropathic pain. Therefore, appropriate suppression of inflammation is a key factor for treating the radiculopathy caused by intervertebral disk (IVD) degeneration. Resveratrol, a key component of red wine, has been suggested to exhibit anti-inflammatory properties in vitro and in vivo. However, the effects of resveratrol on NP-mediated pain in vivo have not been studied. The aim of the present study was to investigate whether resveratrol may be useful in treating NP-mediated pain in an autologous NP model of radiculopathy. A total of 36 adult male Sprague-Dawley rats were allocated randomly into sham (group I), saline-treated (group II) and resveratrol-treated (group III) groups. Animal behavior in response to non-noxious mechanical stimulation with von Frey filaments was compared at days 0 (baseline), 3, 7, 14 and 21 following surgery. The expression of proinflammatory cytokines such as tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1) were assessed at days 7 and 14. The data showed that resveratrol exhibited an anti-inflammatory effect on the expression of proinflammatory cytokines. Compared with group II, the expression of TNF-α and IL-1 was significantly decreased at each time point in group III. In addition, resveratrol significantly reduced pain behavior triggered by the application of NP tissue on the dorsal root ganglion for up to 14 days. These data suggest that resveratrol has potential for the treatment of NP-mediated pain, indicating a potential clinical application. [ABSTRACT FROM AUTHOR]

Background: A prospective cohort study was performed to evaluate the clinical and radiological outcomes following posterior lumbar interbody fusion (PLIF) in patients treated with a PEEK cage compared to those treated with an autologous cage using the lumbar spinous process and laminae (ACSP).Methods: Sixty-nine consecutive patients with lumbar degenerative disc disease were randomly assigned to either a PEEK cage (group A, n = 34) or an ACSP (group B, n = 35). Monosegmental PLIF was performed in all patients. Mean lumbar lordosis, mean disc height, visual analog scale (VAS) scores, functional outcomes, fusion rates and complication rates were recorded and compared. The patients were followed postoperatively for a minimum of 2 years.Results: Successful radiographic fusion was documented in all patients. No flexion-extension hypermobility or pedicle screw loosening or breakage occurred during the follow-up period. No significant difference existed between the 2 groups when comparing the mean lumbar lordosis, mean disc height, visual analog scale (VAS) scores, functional outcomes, fusion rates or complication rates. Overall satisfactory results were achieved in both groups.Conclusions: The results suggest that the ACSP appears to be equally as safe and effective as the PEEK cage.Trial Registration: ISRCTN25558534 . Retrospectively registered 16/02/2016. [ABSTRACT FROM AUTHOR]

Aim of the study: Recent studies have suggested that k-RAS mutations are related to the response to epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitions (TKIs) in advanced non-small cell lung cancer (NSCLC) treatment. The aim of this meta-analysis was to assess the relationship between smoking history and k-RAS mutations in NSCLC treated with TKIs. Material and methods: We searched MEDLINE and Web of Science up to 15 March 2014. The pooled relative risk (RR) was estimated by using fixed effect model or random effect model, according to heterogeneity between studies. We also carried out power analyses. Results: We identified 12 studies with 1193 patients, including 196 patients (16.4%) with k-RAS mutations. The pooled k-RAS mutations incidence was 22.8% (174/764) in patients with smoke expose vs. 5.4% (23/429) in those with no smoke exposure. The pooled RR was 2.991 (95% CI: 1.884- 4.746; Z = 4.65, p = 0.000). No publication bias was found (Begg's test: z = 1.09, p = 0.274 and Egger's test: t = 1.38, p = 0.201). In subgroup analyses, the pooled RR was 3.336 (95% CI: 1.925-5.779; Z = 4.30, p = 0.000) in the Caucasian subgroup, while in the Asian subgroup the pooled RR was 2.093 (95% CI: 0.909-4.822; Z = 1.73, p = 0.083), but the sample size was underpowered (0.465). Conclusions: The current meta-analysis found that smoking was related to increased incidence of k-RAS mutations in non-small cell lung cancer treated with TKIs. This may be further evidence that smoking will lead to a worse prognosis in NSCLC patients treated with TKIs. [ABSTRACT FROM AUTHOR]

A new chromene derivative, 2-(4',8'-dimethylnona-3'E,7'-dienyl)-8-hydroxy-2,6-dimethyl-2H-chromene (1) together with four known natural products, methylfarnesylquinone (2), isololiolide (3), pheophytin a (4), and β-carotene (5) were isolated from the brown alga Homoeostrichus formosana. The structure of 1 was determined by extensive 1D and 2D spectroscopic analyses. Acetylation of 1 yielded the monoacetylated derivative 2-(4',8'-dimethylnona-3'E,7'-dienyl)-8-acetyl-2,6-dimethyl-2H-chromene (6). Compounds 1-6 exhibited various levels of cytotoxic, antibacterial, and anti-inflammatory activities. Compound 2 was found to display potent in vitro anti-inflammatory activity by inhibiting the generation of superoxide anion (IC50 0.22 ± 0.03 μg/mL) and elastase release (IC50 0.48 ± 0.11 μg/mL) in FMLP/CB-induced human neutrophils. [ABSTRACT FROM AUTHOR]

Background This nationwide population-based study investigated the risk of Parkinson's disease (PD) after zolpidem use in patients with sleep disturbance using the National Health Insurance Research Database (NHIRD) in Taiwan. Material and methods In total, 59,548 adult patients newly diagnosed with sleep disturbance and who used zolpidem were recruited as the study cohort, along with 42,171 subjects who did not use zolpidem as a comparison cohort from 2002 to 2009. Each patient was monitored for 5 years, and those who subsequently had PD were identified. A Cox proportional hazards model was used to compare the risk of PD between the study and comparison cohorts after adjusting for possible confounding risk factors. Results The patients who received zolpidem had a higher cumulative rate of PD than those who did not receive zolpidem during the 5-year follow-up period (1.2% vs. 0.5%, P < 0.001). The adjusted hazard ratios were 1.10 (95% CI, 0.88-1.37), 1.41 (95% CI, 1.17-1.72), and 1.27 (95% CI, 1.05-1.55) for zolpidem use with 28-90, 91-365, and more than 365 cumulative defined daily doses (cDDDs), respectively, compared to those who did not use zolpidem. Conclusions Among the patients with sleep disturbance, zolpidem use increased the risk of PD after 5 years of follow-up. Further mechanistic research of zolpidem effect in PD is needed. [ABSTRACT FROM AUTHOR]

T cell functional exhaustion during chronic hepatitis B virus (HBV) infection may contribute to the failed viral clearance; however, the underlying molecular mechanisms remain largely unknown. Here we demonstrate that jumonji domain-containing protein 6 (JMJD6) is a potential regulator of T cell proliferation during chronic HBV infection. The expression of JMJD6 was reduced in T lymphocytes in chronic hepatitis B (CHB) patients, and this reduction in JMJD6 expression was associated with impaired T cell proliferation. Moreover, silencing JMJD6 expression in primary human T cells impaired T cell proliferation. We found that JMJD6 promotes T cell proliferation by suppressing the mRNA expression of CDKN3. Furthermore, we have identified platelet derived growth factor-BB (PDGF-BB) as a regulator of JMJD6 expression. PDGF-BB downregulates JMJD6 expression and inhibits the proliferation of human primary T cells. Importantly, the expression levels of JMJD6 and PDGF-BB in lymphocytes from CHB patients were correlated with the degree of liver damage and the outcome of chronic HBV infection treatment. Our results demonstrate that PDGF-BB and JMJD6 regulate T cell function during chronic HBV infection and may provide insights for the treatment strategies for CHB patients. [ABSTRACT FROM AUTHOR]

Pulmonary embolism (PE) is associated with atrial fibrillation (AF). This study sought to explore if the CHADS2 score could predict the prognosis of PE in patients with AF. In a tertiary hospital, 4,288 consecutive patients with diagnosis of PE were screened. In total, 305 patients with PE had AF and were included in this retrospective study. In-hospital outcome was defined as at least one of the following: death from any cause, need for intravenous catecholamine administration, endotracheal intubation, cardiopulmonary resuscitation, or thrombolytic therapy. The in-hospital outcome occurred in 10.2% of the patients. Patients with adverse outcome had higher CHADS2 score, CHA2DS2-VASc score, and simplified pulmonary embolism severity index (sPESI) score. The area under the receiver operating characteristics curve was 0.66, 0.62, and 0.71 for CHADS2 score, CHA2DS2-VASc score, and sPESI score, respectively, in predicting in-hospital outcome. The incidence of in-hospital outcome was 3.4 and 14.4% in sPESI = 0 and sPESI ⩾1 groups (p < 0.01). CHADS2 also had good predictive value with the incidence of in-hospital outcome, being 4.6% in CHADS2 < 2 and 14.3% in CHADS2 ⩾ 2 groups (p < 0.01). The incidences of in-hospital outcome were 2.6, 4.8, 7.4, and 17.3% in patients with sPESI = 0 and CHADS2 < 2, sPESI = 0 and CHADS2 ⩾ 2, sPESI ⩾ 1 and CHADS2 < 2, and sPESI ⩾ 1 and CHADS2 ⩾ 2 (p < 0.01), respectively. In multivariable analysis, CHADS2 (odds ratio: 1.50; 95% confidence interval: 1.11-2.02; p < 0.01) was an independent predictor of inhospital adverse outcome. High CHADS2 score could predict worse in-hospital outcome in patients with PE and AF. [ABSTRACT FROM AUTHOR]

Background: Due to improvements in imaging and radiological techniques as well as the use of chemotherapy, distant metastasis has become the predominant mode of treatment failure in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Platinum-based systemic chemotherapy has shown survival benefits and is now the standard strategy for systemic therapy in patients with LA-NPC. Notably, the third-generation platinum reagent lobaplatin has shown anti-tumor effects in several solid tumors with lower incidences of gastrointestinal, hepatic and renal toxicity relative to other platinum drugs. However, the safety and efficacy of lobaplatin as a first-line regimen in patients with LA-NPC are undetermined.Methods: Patients with stage III-IVa-b NPC received lobaplatin at a dose of 30 mg/m2 on days 1 and 22 combined with a continuous 120-h intravenous injection of 5-fluorouracil at a dose of 4 g/m2 followed by lobaplatin at a dose of 50 mg/m2 on days 43 and 64 concomitant with intensity-modulated radiation therapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.3.0, respectively. Kaplan-Meier analysis was used to calculate survival rates.Results: Fifty-nine patients were enrolled, and 44 patients (74.6%) received allocated cycles of chemotherapy. The objective response rates were 88.1% (95% confidence interval [CI], 0.77 to 0.95) and 100% after induction chemotherapy (ICT) and concurrent chemoradiotherapy (CRT), respectively. With a median follow-up period of 44 months, the 3-year estimated progression-free survival and overall survival were 86.4% (95% CI, 69.8 to 98.8) and 94.9% (95% CI, 89.5 to 100), respectively. The most common grade 3-4 toxicities were neutropenia (8.5%) and thrombocytopenia (40.7%) after ICT and CRT, respectively.Conclusion: Lobaplatin combined with 5-fluorouracil followed by lobaplatin-RT treatment showed encouraging anti-tumor effects with tolerable toxicities in patients with LA-NPC. Randomized controlled trials of lobaplatin in patients with LA-NPC are warranted.Trial Registration: This trial was registered with the Chinese Clinical Trials Registry and approved on March 31st, 2012, number ChiCTR-ONC-12002060 . [ABSTRACT FROM AUTHOR]

Browning of white adipose tissue (WAT) has been highlighted as a new possible therapeutic target for obesity, diabetes and lipid metabolic disorders, because WAT browning could increase energy expenditure and reduce adiposity. The new clusters of adipocytes that emerge with WAT browning have been named ‘beige’ or ‘brite’ adipocytes. Recent reports have indicated that the renin-angiotensin system (RAS) plays a role in various aspects of adipose tissue physiology and dysfunction. The biological effects of angiotensin II, a major component of RAS, are mediated by two receptor subtypes, angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R). However, the functional roles of angiotensin II receptor subtypes in WAT browning have not been defined. Therefore, we examined whether deletion of angiotensin II receptor subtypes (AT1aR and AT2R) may affect white-to-beige fat conversion in vivo. AT1a receptor knockout (AT1aKO) mice exhibited increased appearance of multilocular lipid droplets and upregulation of thermogenic gene expression in inguinal white adipose tissue (iWAT) compared to wild-type (WT) mice. AT2 receptor-deleted mice did not show miniaturization of lipid droplets or alteration of thermogenic gene expression levels in iWAT. An in vitro experiment using adipose tissue-derived stem cells showed that deletion of the AT1a receptor resulted in suppression of adipocyte differentiation, with reduction in expression of thermogenic genes. These results indicate that deletion of the AT1a receptor might have some effects on the process of browning of WAT and that blockade of the AT1 receptor could be a therapeutic target for the treatment of metabolic disorders. [ABSTRACT FROM AUTHOR]

Objective: Platinum-based chemotherapy in combination with radiotherapy is a standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma (NPC). This study aimed to investigate the long-term efficacy and tolerability of inductive chemotherapy with docetaxel plus carboplatin (TC) or 5-fluorouracil plus carboplatin (FC) followed by concurrent radiation therapy in patients with NPC. Methods: Patients (N=88) were randomized to receive TC or FC as inductive therapy followed by concurrent radiotherapy (60-70 Gy) with two cycles of carboplatin (area under the curve =5 mg·h/L). Patients were followed up for 8 years. Primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), toxicity, tumor response, distant metastasis-free survival, and local recurrence-free survival. Results: At the end of the follow-up period, 31 patients died, 32 had disease progression, eleven had cancer recurrence, and 25 had distant metastasis. Overall, there was no difference between treatment groups with regard to response or survival. We found that following induction and concurrent chemoradiotherapy, the majority of patients showed a complete response (~96%-98% for induction therapy and 82%-84% for comprehensive therapy) to both therapies. PFS and OS were also similar between groups. The rate of PFS was 63.6% for both FC and TC and that of OS was 65.9% and 63.5%, respectively. The overall incidence of grade 3-4 adverse events in the TC group (20.5%) was higher than in the FC group (10.7%). Neutropenia and leukopenia were the most common grade 3-4 adverse events in the TC group, and mucositis was the most common in the FC group. Conclusion: These data indicate that TC and FC therapies have similar efficacy in treating locally advanced NPC and both are well tolerated. [ABSTRACT FROM AUTHOR]

Chronic cerebral hypoperfusion is considered to be a pivotal contributing factor of cognitive impairments that occur in vascular dementia and Alzheimer's disease, and ideal drug treatment for these diseases is unavailable. Hence, this study was designed to investigate the protective effects of icariin, a major constituent of flavonoids from the Chinese medicinal herb Epimedium brevicornum , on cognitive impairments and neuronal morphological damage induced by permanent occlusion of bilateral common carotid arteries (BCCAO) in rats, and further explore the potential mechanisms. This study found that BCCAO could induce cognitive deficits and neuronal morphological damage, along with deposition of beta-amyloid (Aβ) in rat hippocampus. However, oral administration of icariin twice per day for 23 days might attenuate cognitive deficits and neuronal morphological damage induced by BCCAO. Subsequently, icariin decreased the level of Aβ in rat hippocampus subjected to BCCAO. Administration of icariin reduced the expressions of amyloid precursor protein (APP), beta-secretase 1 (BACE1), and increased the expressions of insulin-degrading enzyme (IDE) and a disintegrin and metalloproteinase domain 10 (ADAM10) in rat hippocampus. Furthermore, icariin afforded beneficial actions in suppressing transforming growth factor-β 1 (TGF-β 1 ) signaling via inhibition of Smad2/3 phosphorylation. In summary, icariin is effective in improving cognitive deficits and hippocampus morphological alterations subjected to BCCAO. This protection appears to be due to the decreased expressions of both APP and BACE1, and the increased expressions of both IDE and ADAM10, resulting in a decrease in the level of insoluble Aβ fragments in rat hippocampus. Inhibitions of TGF-β 1 signaling and Smad2/3 phosphorylation are involved in the course. [ABSTRACT FROM AUTHOR]