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The oxidative-antioxidative status is closely associated with the progression of systemic lupus erythematosus (SLE), and oxidative stress is customarily found in patients with SLE. N-acetylcysteine (NAC), a typical antioxidant, is reliable and often applied for clinical treatment. Lupus nephritis (LN) is a kidney disorder associated with SLE, but the treatment of LN with antioxidants is rarely documented. The present report describes two cases of early-stage LN that were orally treated with 1,200 mg NAC in addition to the standard therapy with hydroxychloroquine and calcitriol. Following the NAC administration, the glutathione level largely increased while the level of the lipid peroxidation biomarker 8-iso-prostaglandin F2α declined in both cases. In addition, the routine blood counts, 24-h urine protein, erythrocyte sedimentation rate and the SLE disease activity index were markedly improved. In conclusion, the present report of two cases has shown that NAC, as an antioxidant, may exert a beneficial effect to modulate the oxidative status in LN; however, the underlying mechanisms require further investigation. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a multifactorial chronic disease primarily characterized by the degeneration of articular cartilage. Currently, there is a lack of effective treatments for OA other than surgery. The exploration of the mechanisms of occurrence is important in exploring other new and effective treatments for OA. The current evidence shows that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays a vital role in cytogenesis and is involved in OA progression. The terms "JAK2", "STAT3", and "Osteoarthritis"were used in a comprehensive literature search in PubMed to further investigate the relationship between the JAK2/STAT3 signaling pathway and OA. This review focuses on the role and mechanism of JAK2/STAT3 signaling in cartilage degradation, subchondral bone dysfunction, and synovial inflammation. In addition, this review summarizes recent evidence of therapeutic approaches to treat OA by targeting the JAK2/STAT3 pathway to accelerate the translation of evidence into the progression of strategies for OA treatment. Aq2kuF8RhmhLRVBTwsgJsc Video abstract [ABSTRACT FROM AUTHOR]

Supraventricular arrhythmias (SVA) may be risk factors of prognosis in patients with pulmonary arterial hypertension. SVA are increasingly reported in patients with pulmonary hypertension, but little is known about their incidence and outcomes for patients with idiopathic pulmonary arterial hypertension (IPAH) in a large cohort. In this 6-year prospective multicenter study, 280 patients with IPAH were enrolled to investigate the incidence of SVA and assess risk factors, clinical manifestation, management, and impact on survival. The cumulative 6-year incidence of SVA was 15.8%. The most common types of SVA were atrial fibrillation (n = 16) and atrial flutter (n = 13), followed by atrial tachycardia (n = 11). Most episodes of SVA were associated with significant clinical deterioration and right-sided cardiac failure. Sinus rhythm was successfully restored in most patients, resulting in clinical recovery. Increased right ventricular diameter, left atrial area, and higher right atrial pressure and pulmonary vascular resistance were associated with increased risk for experiencing SVA. SVA predicted a greater risk for mortality in a stepwise forward Cox analysis (hazard ratio 4.757, 95% confidence interval 2.695 to 8.397, p <0.001). Kaplan-Meier survival curves showed that patients with SVA, mainly permanent SVA, had a lower survival rate than those who did not develop SVA (p = 0.008). In conclusion, SVA often lead to clinical deterioration and may be associated with an increased risk for death in a large cohort of patients with IPAH. Restoration and maintenance of sinus rhythm are important treatment goals in patients with IPAH. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine the efficacy of sorafenib in preventing and treating tumor recurrence after liver transplantation in patients with primary hepatic carcinoma exceeding the Milan criteria. Methods: Thirty patients with primary hepatic carcinoma exceeding the Milan criteria underwent liver transplantation at our hospital between March 2008 and June 2010. Matched for age and gender, the patients were randomized to treatment with sorafenib 400 mg bid or capecitabine (control group, 1500 mg bid, administered for 2 weeks followed by a 2-week rest interval in each cycle). Treatments were discontinued 18 months after transplantation if no recurrence occurred. Patients who experienced tumor recurrence continued their allocated treatment until they were deemed no longer suitable for the medication. Sorafenib and capecitabine were stopped or their dose was reduced in patients with severe adverse reactions. Results: The one-year recurrence rates were 53.3% and 86.6% in patients treated with sorafenib and capecitabine, respectively (χ2 = 3.968, P < 0.05), and the one-year survival rates were 93.3% and 46.6%, respectively (χ2 = 7.777, P < 0.05). Mean survival time was significantly longer in the sorafenib group (24.6 ± 1.7 [range 7-28] months) than in the capecitabine group (16.4 ± 2.7 [range 5-34], months (χ2 = 7.154, P < 0.05). Most treatment-emergent adverse reactions in both treatment groups were of grade 1 or 2 in severity. The incidence of diarrhea and hand-foot syndrome tended to be higher in the sorafenib group. Conclusion: For patients with primary hepatic carcinoma exceeding the Milan criteria, sorafenib may reduce or delay tumor recurrence after liver transplantation and prolong patient survival, with tolerable side effects. [ABSTRACT FROM AUTHOR]

To compare the efficacy and toxicities of pemetrexed plus platinum with other platinum regimens in patients with previously untreated advanced non-small cell lung cancer (NSCLC). Methods: A meta-analysis was performed using trials identified through PubMed, EMBASE, and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included overall survival (OS), progression-free survival (PFS), response rate (RR), and different types of toxicity. Hazard ratios (HRs), odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled using RevMan software. Results: Four trials involving 2,518 patients with previously untreated advanced NSCLC met the inclusion criteria. Pemetrexed plus platinum chemotherapy (PPC) improved survival compared with other platinum-based regimens (PBR) in patients with advanced NSCLC (HR = 0.91, 95% CI: 0.83-1.00, p = 0.04), especially in those with non-squamous histology (HR = 0.87, 95% CI: 0.77-0.98, p = 0.02). No statistically significant improvement in either PFS or RR was found in PPC group as compared with PBR group (HR = 1.03, 95% CI: 0.94-1.13, p = 0.57; OR = 1.15, 95% CI: 0.95-1.39, p = 0.15, respectively). Compared with PBR, PPC led to less grade 3-4 neutropenia and leukopenia but more grade 3-4 nausea. However, hematological toxicity analysis revealed significant heterogeneities. Conclusion: Our results suggest that PPC in the first-line setting leads to a significant survival advantage with acceptable toxicities for advanced NSCLC patients, especially those with non-squamous histology, as compared with other PRB. PPC could be considered as the first-line treatment option for advanced NSCLC patients, especially those with non-squamous histology. [ABSTRACT FROM AUTHOR]

Background and objectives: 1,1′-Dimethyl-4,4′-bipyridinium dichloride (Paraquat) poisoning remains a significant global health problem. Despite noteworthy research and clinical efforts worldwide in the last few decades, little improvement has been made in reducing fatality from Paraquat poisoning with conventional treatment strategies. We herein report a case of successful management of Paraquat poisoning by Xuebijing, a newly developed injection concocted from multiple traditional Chinese medicinal herbs. Settings/location, subjects, and interventions: A 25-year-old male patient was brought to the Emergency Department at the First Affiliated Hospital of Jilin University in Changchun, China approximately 23 hours after ingestion of approximately 50 mL of 20% (w/v) Paraquat in a suicide attempt. On admission, the patient presented with clinical symptoms as well as significantly abnormal results in the liver and kidney function tests that were typical of severe Paraquat poisoning. Following the routine emergency procedures for pesticide poisoning to minimize the poison exposure and relieve the poisoning symptoms, an intravenous drip of Xuebijing together with dexamethasone was given daily to the patient until discharge 10 days after admission. The patient was followed up for 15 months after discharge, during which monthly chest radiography was performed. Treatment outcomes: At the time of discharge, the patient had recovered well: His symptoms of poisoning in the mouth and gastrointestinal tract were all diminishing; his liver and kidney functions were recovering with the major test parameters improving; his chest radiograph was clear, showing no signs of pulmonary fibrosis. During the postdischarge follow-up period, the monthly chest radiographs were all normal. Conclusions: This case report suggests that Xuebijing has great potential as a novel effective alternative to the conventional management of Paraquat poisoning. This potential needs to be further evaluated in a substantially larger number of clinical cases in the future. [ABSTRACT FROM AUTHOR]

Pharmacological therapy, botulinum toxin injection, pneumatic dilatation, and surgical myotomy are the primary therapeutic modalities for achalasia, for which laparoscopic myotomy is recommended as state-of-the-art therapy. However, its efficacy and safety remain unclear compared with other approaches in the treatment of achalasia. We searched electronic databases (MEDLINE, EMBASE, Cochrane Central Registry of Controlled Trials, LILACS-Latin American, Caribbean health science literature, and Science Citation Index Expanded) for randomized controlled trials to evaluate which therapeutic measures are temporary and reversible and which measures are definitive and effective by pooling data including remission rate, relapse rate, complications, and adverse effects. Seventeen studies with 761 patients met our inclusion criteria. There was better remission rate in pneumatic dilation than in botulinum toxin injection for initial intervention [relative risk (RR) 2.20, 95% confidence interval (CI) 1.51–3.20], Pneumatic dilation had lower relapse rate than did botulinum toxin injection (RR 0.12, 95% CI 0.04–0.32). Compared with pneumatic dilation, laparoscopic myotomy further increased remission rate (RR 1.48, 95% CI 1.48–1.87), and reduced clinical relapse rate (RR 0.14, 95% CI 0.04–0.58), and there was no difference in complication rate (RR 1.48, 95% CI 0.37–5.99). Based on limited randomized and controlled trials, laparoscopic myotomy is the preferred method for patients with achalasia. Future trials should investigate whether laparoscopic myotomy combined with different modalities of fundoplication is superior to isolated laparoscopic myotomy. [ABSTRACT FROM AUTHOR]

A series of 4-substituted methoxybenzoyl-aryl-thiazoles (SMART) have been discovered and synthesized as a result of structural modifications of the lead compound 2-arylthiazolidine-4-carboxylic acid amides (ATCAA). The antiproliferative activity of the SMART agents against melanoma and prostate cancer cells was improved from μM to low nM range compared with the ATCAA series. The structure−activity relationship was discussed from modifications of “A”, “B”, and “C” rings and the linker. Preliminary mechanism of action studies indicated that these compounds exert their anticancer activity through inhibition of tubulin polymerization. [ABSTRACT FROM AUTHOR]

[Objective] To observe the clinical effects of Zhuang Ethnomedicine "antilipemic and liver protecting decoction" on 78 cases of nonalcoholic fatty liver diseases, and to provide new methods for the clinical treatment of nonalcoholic fatty liver diseases. [Methods] The 78 patients were randomly divided into two groups of treatment group ( antilipemic and liver protecting decoction) and control group ( fenofibrate tablets), with 39 cases in each group. After treatment for 12 weeks, changes of hepatic function, blood lipid and B-ultrasonography were observed. [Results] Alamine aminotransferase (ALT), aspartate transaminase (AST), glutamyltransferase (γ-GT), serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) were all decreased in two groups after treatment. However, treatment group had significant statistical significance with control group (P <0. 05) . Results of B-ultrasonography detection after treatment showed that the fatty liver degrees improved in two groups; and treatment group was superior to control group (P < 0. 05). [Conclusions] Antilipemic and liver protecting decoction showed obvious curative effects on nonalcoholic fatty liver diseases, which should be applied and extended in clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of eradicating Helicobacter pylori on dyspeptic symptoms in patients with functional dyspepsia in China. Data sources: Randomized controlled trials conducted in China and those published between 1989 and April 2007. Review methods: The articles were retrieved from Chinese biomedicine Web database and Chinese scientific Journals database using proper MESH headings and assessed by two independent investigators according to established inclusion criteria. The characteristics of chosen articles were displayed for further analysis, and summary odds ratio were calculated to determine the overall effect of H. pylori eradication. All the data were entered and analyzed usingreview manager 4.1, and p < .05 was defined as statistically significant in all analysis. Results: Seven qualified trials were enrolled, and the summary odds ratio for improvement in dyspeptic symptoms in patients with functional dyspepsia in whom H. pylori was eradicated was 3.61 (95%CI: 2.62, 4.98, p < .00001). The difference in the follow-up period did not influence the final outcomes. Conclusions: An improvement in dyspeptic symptoms occurred among Chinese patients with functional dyspepsia in whom H. pylori was eradicated. [ABSTRACT FROM AUTHOR]

Aim: To determine efficacy and clinical predictors of stone fragmentation when using slow-rate shock wave lithotripsy (SWL). Patients and Methods: In total, 116 patients with radiopaque urinary tract stones were randomized into two groups: 57 patients were treated with SWL at 90 shocks/min, and 59 patients were treated with SWL at 120 shocks/min. The efficacy of SWL was evaluated within 1 month after treatment. Patient characteristics, features of stones, and SWL conditions were reviewed. Success rates relating to individual parameters were assessed by using chi-square and Student t tests. All factors were further entered into multivariate logistic regression analysis. Results: There were no statistically significant differences between the two groups with regard to age, sex, site and size of the stones, renal function, and total number of shock waves. In univariate analysis, the success rate was significantly related to shock wave frequency (p = 0.023), length and width of the stones (p < 0.001), total number of shock waves (p = 0.047), and age (p = 0.049). In multivariate analysis, however, only shock wave rate and stone length remained statistically significant (p = 0.021 and p = 0.046, respectively). The overall success rate was significantly higher in the group treated with 90 shocks/min (p = 0.02). However, this higher success rate was statistically significant only in patients with a stone length ≥10 mm (50.0 vs. 18.5%, p = 0.019). Conclusion: SWL at 90 shocks/min yielded better outcomes than SWL at 120 shocks/min, particularly in patients with stone lengths ≥10 mm. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors, and effective therapeutic interventions for PDAC are limited. While Corynoxine (Cory) and its isomer Cory B have been identified as autophagy inducers in neuronal cells, it remains unclear whether they exert a therapeutic effect on PDAC. Here, we performed cell counting kit-8 (CCK8), colony formation, 5-Ethynyl-2'-deoxyuridine (EDU) staining, TUNEL, and flow cytometry assays to evaluate the effects of Cory on PDAC. Western blotting was conducted to analyze the protein expression levels. We showed that Cory and Cory B enhanced cell growth arrest and pro-apoptotic effects of gemcitabine (Gem) on Gem-resistant Panc-1 cells. Mechanistic studies revealed that increased production of reactive oxygen species (ROS) and p38 activation were closely associated with Cory and Cory B-induced cell death. Pretreatment with ROS scavenger N-acetylcysteine blocked Cory and Cory B-induced cell death. Moreover, p38 inhibitor SB203580 prevented cell death induced by Cory and Cory B. Overall, Cory and Cory B increase the sensitivity of Gem-resistant Panc-1 cells to Gem through the activation of ROS-dependent p38 signaling pathway. Our results indicate that Cory and Cory B might be potential approaches for PDAC therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Most patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) fail to complete bacillus Calmette-Guérin (BCG) instillation due to toxicity or shortage. Our retrospective study aimed to assess the efficacy of intravesical chemotherapy replacement at the time of BCG interruption. We confirmed the chemotherapy replacement group had a better three-year bladder recurrence-free survival (RFS) than the BCG discontinuation group. Chemotherapy replacement is then a helpful strategy in patients with NMIBC facing BCG treatment stoppage. Background: To evaluate the efficacy of intravesical chemotherapy replacement in patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), who underwent bacillus Calmette-Guérin (BCG) instillation but discontinued due to global shortages or toxicity of BCG. Methods: This retrospective study included patients with intermediate- and high-risk NMIBC who received BCG intravesical instillation. Those who discontinued the treatment were divided into the pure BCG group and chemotherapy replacement group. Comparisons between these groups were performed. The primary endpoint was bladder recurrence-free survival (RFS). Results: A total of 480 patients were included. Baseline characteristics were similar between groups, but the total instillation times were higher in the chemotherapy replacement group than in the pure BCG group (n = 14.9 vs. 10.5). The chemotherapy replacement group had a better three-year RFS (p = 0.022). On multivariate analysis, the pure BCG group had significantly increased all-time and 3-year recurrences (hazard ratio 2.015 and 2.148) compared to the chemotherapy replacement group. Conclusions: Chemotherapy replacement has a better three-year RFS than no instillation in patients with intermediate- and high-risk NMIBC who received BCG instillation but facing treatment stoppage. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to investigate the clinical effectiveness of staging radioactive particle implantation guided by computed tomography (CT) and fiber-optic bronchoscopy in treating cancerous large airway stenosis. Methods: A total of 102 patients were included; 57 had undergone staging radioactive particle implantation guided by CT and fiber bronchoscopy and 45 did not. Patients were evaluated by CT and fiber-optic bronchoscopy to determine the feasibility of the implantation of radioactive seeds for the treatment of cancerous large airway stenosis. The treatment planning system (TPS) was used to plan the doses. Radioactive seeds were implanted using fiber-optic bronchoscopy. One week later, CT-guided implantation of radioactive seeds was performed. Results: The clinical evaluation showed complete, partial, slight, and non-response in 38, 14, 5, and 0 patients, respectively. None of the patients were found with serious complications. The diameter of the affected airway, Karnofsky score, dyspnea index, survival, and quality of life of the patients in both groups was significantly higher and significantly different after the treatment (P < 0.05). The dyspnea index was significantly lower in the treatment group as compared with the control group (P < 0.001). Conclusion: CT- and fiber bronchoscopy-guided staging radioactive particle implantation has definite treatment effectiveness in treating cancerous large airway stenosis. It should be widely used in clinical practices. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Acupuncture for Chronic Knee Pain: A Randomized Clinical Trial," R. S. Hinman et al. in a 2014 issue of "JAMA".

Background: Aconiti brachypodi Radix (Xue-shang-yi-zhi-hao) has been prescribed to manage chronic pain, arthritis, and traumatic injuries. Bullatine A, a C20-diterpenoid alkaloid, is one of its principle effective compounds. This study aimed to investigate the anti-hypersensitivity of bullatine A in a variety of rat pain models and explore its mechanisms of action.Methods: Rat neuropathic pain, inflammatory pain, diabetic neuropathic pain, and bone cancer pain models were used. Dynorphin A and pro-inflammatory cytokines were measured in the spinal cord and cultured primary microglia. Double immunofluorescence staining of dynorphin A and glial and neuronal cellular markers was also measured in the spinal cord.Results: Subcutaneous and intrathecal injection of bullatine A dose-dependently attenuated spinal nerve ligation-, complete Freud's adjuvant-, diabetes-, and bone cancer-induced mechanical allodynia and thermal hyperalgesia, with the efficacies of 45-70 % inhibition, and half-effective doses of 0.9-1.9 mg/kg for subcutaneous injection. However, bullatine A was not effective in blocking acute nociceptive response in the normal condition. Bullatine A specifically stimulated dynorphin A expression in microglia in the spinal cord in vivo and cultured primary microglia in vitro; the stimulatory effects were completely inhibited by the microglial inhibitor minocycline. In contrast, bullatine A did not have an inhibitory effect on peripheral nerve injury- or lipopolysaccharide-induced pro-inflammatory cytokine expression. The spinal anti-allodynic effects of bullatine A were entirely blocked by intrathecal injection of minocycline, the specific dynorphin A antiserum, and the selective k-opioid receptor antagonist.Conclusions: We, for the first time, demonstrate that bullatine A specifically attenuates pain hypersensitivity, regardless of the pain models employed. The results also suggest that stimulation of spinal microglial dynorphin A expression mediates bullatine A anti-nociception in pain hypersensitivity conditions. [ABSTRACT FROM AUTHOR]

Eupatilin, one of the major flavonoids in Artemisia asiatica Nakai (Asteraceae), has been reported to possess antitumor properties. However, thus far there have been no reports regarding the effects of eupatilin on glioma. Therefore, in the current study the effects of eupatilin on glioma and the underlying molecular mechanism were explored. The effect of eupatilin on cell viability was detected by the MTT assay. Cell invasion and migration were performed with Transwell assays and cell apoptosis was determined by flow cytometric analysis. Notch-1 knockdown cells were established by transfection with Notch-1 small interfering RNA (siRNA). The expression levels of Notch-1 were detected by quantitative reverse transcription-polymerase chain reaction and western blotting. The results of the present study indicated that eupatilin exhibits an anticancer effect on glioma cells. Eupatilin inhibited proliferation, reduced cell invasion and migration, and promoted the apoptosis of glioma cells. Additionally, it suppressed Notch-1 expression. Knockdown of Notch-1 by siRNA contributed to the inhibitory effect of eupatilin on proliferation and invasion of glioma cells. In conclusion, eupatilin had an inhibitory effect on proliferation, invasion and migration, and promoted apoptosis of glioma cells through suppression of the Notch-1 signaling pathway. Therefore, eupatilin may have potential as an effective agent for the treatment of glioma. [ABSTRACT FROM AUTHOR]

Objective To explore the relationship of phosphatase and tensin homolog (PTEN) with cell proliferation in cervical cancer cells so as to further analyze the role of PTEN and its underlying mechanisms in the pathogenesis and progression of cervical cancer cells. Methods The expression of PTEN was detected in different cervical cancer cell lines by Western blotting. Then the overexpression vector of PTEN was constructed and transfected into cervical cancer cells with Lipofectemine 2000. The proliferative index was estimated by cell counting and MTT. The contents of glucose, glutamine and lactic acid were detected by the BioProfile FLEX analyzer to evaluate the effect of PTEN on the cell metabolism. The proteins related to cell metabolism were measured by Western blotting. Results The expression of PTEN was down-regulated in cervical cancer cell lines compared to that of normal cervical epithelium cells. The overexpression PTEN vector was transfected into HeLa and C33A cells, resulting in the up-regulation of PTEN. Enforced expression of PTEN inhibited the proliferation of cervical cancer cells, which was confirmed by cell counting and MTT (P<0.05). We also found that glucose and glutamine contents in the medium with PTEN-overexpressing cells were increased, but lactic acid content was decreased. Moreover, PTEN suppressed the expression of pAKT, PFKFB3, PKM2 and GLS in these cells. Conclusion PTEN regulates the proliferation of cervical cancer cells by AKT mediated cell metabolism, providing new insights into novel molecular target for the diagnosis and therapy of cervical cancer. [ABSTRACT FROM AUTHOR]

Anemone flaccida Fr. Schmidt, a family of ancient hopanoids, have been used as traditional Asian herbs for the treatments of inflammation and convulsant diseases. Previous study on HeLa cells suggested that triterpenoid saponins from Anemone flaccida Fr. Schmidt may have potential antitumor effect due to their apoptotic activities. Here, we confirmed the apoptotic activities of the following five triterpenoid saponins: glycoside St-I4a (1), glycoside St-J (2), anhuienoside E (3), hedera saponin B (4), and flaccidoside II (5) on human BEL-7402 and HepG2 hepatoma cell lines, as well as the model of HeLa cells treated with lipopolysaccharide (LPS). We found that COX-2/PGE2 signaling pathway, which plays key roles in the development of cancer, is involved in the antitumor activities of these saponins. These data provide the evidence that triterpenoid saponins can induce apoptosis via COX-2/PGE2 pathway, implying a preventive role of saponins from Anemone flaccida in tumor. [ABSTRACT FROM AUTHOR]

Background Pacing has been proposed as a treatment for patients with hypertrophic obstructive cardiomyopathy (HOCM), but there are few studies with long-term follow-up. We evaluated the long-term effects of dual-chamber pacing therapy for patients with HOCM, and to identify the most prognosis-specific factors for predicting outcome in such treating methods. Methods A total of 37 HOCM patients implanted with dual-chamber pacemakers were enrolled consecutively and followed-up. Thirty-seven cases were followed for 1 year, 26 cases for 2 years, 10 cases for 3 years, and eight cases for 4 years. At each annual point of follow-up after pacemaker implantation, the pacing frequency, pacing threshold, impedance, atrioventricular delay, and cumulative percentage of atrial and ventricular pacing were tested, respectively. In addition, left atrial dimension (LAD), left ventricular end diastolic dimension (LVEDd), left ventricular posterior wall thickness (LVPW), interventricular septum thickness (IVS), left ventricular outflow tract dimension (LVOTd), peak velocity of left ventricular outflow tract (VLVOT), left ventricular outflow tract pressure gradient (LVOTPG), left ventricular ejection fraction (LVEF), and pulmonary artery systolic pressure (PASP) were measured. Mitral valve systolic anterior motion (SAM) was also observed. Pacing parameters and echocardiography indexes before and after pacemaker implantation were dynamically compared. Results Pacing frequency and atrioventricular delay were adjusted to 60-70 beats per minute and 90-180 ms, respectively, in order to ensure the ratio of ventricular pacing was more than 98%. Pacing threshold and pacing impedance were kept in normal ranges. The differences of various pacing parameters were of no statistical significance within the 4 years of follow-up (P > 0.05). Compared with prior to pacing, it was observed that the IVS, VLVOT, and LVOTPG declined significantly (P < 0.01), the LVOTd widened significantly (P < 0.01), and the SAM phenomenon improved obviously (P < 0.01) at 1, 2, 3, and 4 years after pacemaker implantation. Additionally, the changes in LAD, LVEDd, LVPW, LVEF, and PASP were statistically insignificant (P > 0.05). Conclusions The cardiac structural reconstruction in patients with HOCM can be chronically improved by dual-chamber pacing therapy. The IVS, LVOTd, VLVOT, and LVOTPG can be used as sensitive and specific factors in evaluating the long-term effects of dual-chamber pacing therapy for HOCM. (PACE 2013; 36:86-93) [ABSTRACT FROM AUTHOR]

APOBEC3G (A3G) is an antiviral protein that binds RNA and single-stranded DNA (ssDNA). The oligomerization state of A3G is likely to be influenced by these nucleic acid interac- tions. We applied the power of nanoimaging atomic force mi- croscopy technology to characterize the role of ssDNA in A3G oligomerization. We used recombinant human A3G prepared from HEK-293 cells and specially designed DNA substrates that enable free A3G to be distinguished unambiguously from DNA-bound protein complexes. This DNA substrate can be likened to a molecular ruler because it consists of a 235-bp double-stranded DNA visual tag spliced to a 69-nucleotide ssDNA substrate. This hybrid substrate enabled us to use volume measurements to determine A3G stoichiometry in both free and ssDNA-bound states. We observed that free A3G is primarily monomeric, whereas ssDNA-complexed A3G is mostly dimeric. A3G stoichiometry increased slightly with the addition of Mg2+, but dimers still predominated when Mg2+ was depleted. A His-248/His-250 Zn2+-mediated intermolecular bridge was observed in a catalytic domain crystal structure (Protein Data Bank code 31R2); however, atomic force micros- copy analyses showed that the stoichiometry of the A3G- ssDNA complexes changed insignificantly when these residues were mutated to Ala. We conclude that A3G exchanges between oligomeric forms in solution with monomers predominating and that this equilibrium shifts toward dimerization upon binding ssDNA. [ABSTRACT FROM AUTHOR]

The article presents the 2010 guidelines in diagnosing and managing nonalcoholic fatty liver disease (NAFLD). It explains the prevalence of NAFLD in terms of countries and population as well as its risk factors. It mentions that diagnostic criteria include liver biopsy's histological results, mixed hepatocellular steatosis, and vascular blurring seen in abdominal ultrasonography. Furthermore, NAFLD treatment measures include health education, weight gain control, and anti-inflammatory drugs.

Objective: To investigate the role of a functional polymorphism consisting of an aspartic acid (D) repeat located in the asporin gene (ASPN) gene in the susceptibility to and clinical outcome of ankylosing spondylitis (AS). Methods: A total of 374 Chinese patients with ankylosing spondylitis and 421 controls of the same ethnic origin matched for age and sex were included in the study. The asporin D repeat polymorphism was genotyped by polymerase chain reaction with a fluorescent primer. Results: Significant differences between AS patients and controls were detected in the distribution of the 7 alleles found in our population. D14 and D16 alleles were significantly over-represented in AS patients (D14, P=0.001, odds ratio (OR)=1.857, 95% confidence interval(CI) 1.27-2.715; and D16, P< 0.0001, OR=2.605, 95% CI 1.75-3.879). D16 over-representation was more common in early-onset patients than in late-onset patients, although the difference did not reach significance (P= 0.071). Conclusion: The results support a role for an asporin D repeat polymorphism in the susceptibility to AS and an influence of this gene on the outcome of the disease. D14 and D16 allele variants of ASPN might be the susceptibility alleles for AS in the Han Chinese population, whereas the D13 allele variant may have a protective effect on the onset of AS. [ABSTRACT FROM AUTHOR]

Here we report a genetically modified bacteria strain, Salmonella typhimurium Al, selected for anticancer activity in vivo. The strain grows in tumor xenografts. In sharp contrast, normal tissue is cleared of these bacteria even in immunodeficient athymic mice. S. typhimurium Al is auxotrophic (Leu/Arg-dependent) but apparently receives sufficient support from the neoplastic tissue to grow locally. Whether additional genetic lesions are present is not known. In in vitro infection, the GFP-expressing bacteria grew in the cytoplasm of PC-3 human prostate cancer cells and caused nuclear destruction. These effects were visualized in cells labeled with GFP in the nucleus and red fluorescent protein in the cytoplasm. In vivo, the bacteria caused tumor inhibition and regression of xenografts visualized by whole-body imaging. The bacteria, introduced i.v. or intratumorally, invaded and replicated intracellularly in PC-3 prostate cancer cells labeled with red fluorescent protein grafted into nude mice. By day 15, S. typhimurium Al was undetectable in the liver, lung, spleen, and kidney, but it continued to proliferate in the PC-3 tumor, which stopped growing. When the bacteria were injected intratumorally, the tumor completely regressed by day 20. There were no obvious adverse effects on the host when the bacteria were injected by either route. The S. typhimurium Al strain grew throughout the tumor, including viable malignant tissue. This result is in marked contrast to bacteria previously tried for cancer therapy that were confined to necrotic areas of the tumor, which may account in part, for the strain's unique antitumor efficacy. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the treatment of portal cavernous transformation (PVCT). The surgical treatment of 18 patients with PVCT was studied retrospectively. Eight patients underwent mesocaval shunt with artificial grafts, two patients had splenectomy and disconnection, three patients had a central splenorenal shunt, and six patients had a distal splenorenal shunt. There were no deaths or hepatic encephalopathy after operation. Bleeding recurred in two patients (disconnection in one, mesocaval shunt in one). The individualized choice of shunt is ideal for treating PVCT, and the combined procedures of shunt and disconnection are useful. The Rex shunt will be the focus of PVCT surgery in the future. [ABSTRACT FROM AUTHOR]

Delisheng is a widely used antineoplastic agent in China. Although previous studies revealed that Delisheng exhibits numerous pharmacological effects including the inhibition of cancer cell differentiation and enhancement of immune function with the lowest toxicity, the precise anticancer mechanisms of Delisheng in human hepatocellular carcinoma (HCC) cells remains largely unknown. The present study investigated the potential mechanisms underlying the anticancer properties of Delisheng on Hep3B cells. Delisheng demonstrated a strong anti‑proliferation effect on Hep3B cells compared with normal liver HL‑7702 cells, as detected by MTT assays. In addition, Delisheng arrested the cells in G/G1 phase. Furthermore, it exhibited a pro‑apoptotic effect on Hep3B cells, as detected by flow cytometry. When exposed to Delisheng, Hep3B cells demonstrated decreased vascular endothelial growth factor (VEGF) and osteopontin (OPN) and increased endostatin (ES) protein expressions, as detected using immunocytochemistry staining and western blotting. These data suggest that Delisheng induces antiproliferation and apoptosis of Hep3B cells via modulation of VEGF, OPN and ES protein expression. It is hypothesized that Delisheng may be used as a novel anticancer therapeutic in HCC. [ABSTRACT FROM AUTHOR]

In this study, we explored the effects of mesenchymal stem cells (MSCs) from bone marrow overexpressing heme oxygenase-1 (HO-1) on the damaged human intestinal epithelial barrier in vitro. Rat MSCs were isolated from bone marrow and transduced with rat HO-1 recombinant adenovirus (HO-MSCs) for stable expression of HO-1. Colorectal adenocarinoma 2 (Caco2) cells were treated with tumor necrosis factor-α (TNF-α) to establish a damaged colon epithelial model. Damaged Caco2 were cocultured with MSCs, Ad-MSCs, Ad-HO + MSCs or HO-MSCs. mRNA and protein expression of Zona occludens-1 (ZO-1) and human HO-1 and the release of cytokines were measured. ZO-1 and human HO-1 in Caco2 were significantly decreased after treatment with TNF-α; and this effect was reduced when coculture with MSCs from bone marrow. Expression of ZO-1 was not significantly affected by Caco2 treatment with TNF-α, Ad-HO, and MSCs. In contrast, ZO-1 and human HO-1 increased significantly when the damaged Caco2 was treated with HO-MSCs. HO-MSCs showed the strongest effect on the expression of ZO-1 in colon epithelial cells. Coculture with HO-MSCs showed the most significant effects on reducing the expression of IL-2, IL-6, IFN-γ and increasing the expression of IL-10. HO-MSCs protected the intestinal epithelial barrier, in which endogenous HO-1 was involved. HO-MSCs play an important role in the repair process by reducing the release of inflammatory cytokines and increasing the release of anti-inflammatory factors. These results suggested that HO-MSCs from bone marrow were more effective in repairing the damaged intestinal epithelial barrier, and the effectiveness of MSCs was improved by HO-1 gene transduction, which provides favorable support for the application of stem cell therapy in the intestinal diseases. [ABSTRACT FROM AUTHOR]

Arginine-specific mono-ADP-ribosyltransferase 1 (ART1) is an important enzyme that catalyzes arginine-specific mono-ADP-ribosylation. There is evidence that arginine-specific mono-ADP-ribosylation may affect the proliferation of smooth muscle cells via the Rho-dependent signaling pathway. Previous studies have demonstrated that ART1 may have a role in the proliferation, invasion and apoptosis of colon carcinoma in vitro. However, the effect of ART1 on the proliferation and invasion of colon carcinoma in vivo has yet to be elucidated. In the present study, mouse colon carcinoma CT26 cells were infected with a lentivirus to produce ART1 gene silencing or overexpression, and were then subcutaneously transplanted. To observe the effect of ART1 on tumor growth or liver metastasis in vivo, a spleen transplant tumor model of CT26 cells in BALB/c mice was successfully constructed. Expression levels of focal adhesion kinase (FAK), Ras homolog gene family member A (RhoA) and the downstream factors, c-myc, c-fos and cyclooxygenase-2 (COX-2) proteins, were measured in vivo. The results demonstrated that ART1 gene silencing inhibited the growth of the spleen transplanted tumor and its ability to spread to the liver via metastasis. There was also an accompanying increase in expression of FAK, RhoA, c-myc, c-fos and COX-2, whereas CT26 cells with ART1 overexpression demonstrated the opposite effect. These results suggest a potential role for ART1 in the proliferation and invasion of CT26 cells and a possible mechanism in vivo. [ABSTRACT FROM AUTHOR]

Here we explore the T-lymphocyte suppressive and immunomodulatory effects of bone marrow mesenchymal stem cells (BMMSCs) overexpressing heme oxygenase-1 (HO-1) on acute rejection following reduced-size liver transplantation (RLT) in a rat model. The proliferation activity, cell cycle progression, secretion of proinflammatory cytokines, expression of CD25 and CD71 in lymphocytes, and activity of NK cells were found to be significantly lowered, and the proportion of regulatory T cells (Tregs) was found to be increased relative to BMMSCs when Adv-HO-1/BMMSCs were co-cultured with Con A ex vivo; secretion of anti-inflammatory cytokines was significantly higher. When treated with saline, BMMSCs or Adv-HO-1/BMMSCs, post-transplantation rats receiving Adv-HO-1/BMMSCs showed better median survival time, lower rejection activity index, higher anti-inflammatory cytokine levels, lower proinflammatory cytokine levels, more peripheral Tregs, and lower natural killer cell viability. These results suggest that HO-1 enhanced and prolonged the effects of BMMSCs on acute rejection following RLT, with immunomodulatory effects in which adaptive and innate immunity, as well as paracrine signaling, may play important roles. [ABSTRACT FROM AUTHOR]

Steroid receptor coactivator 3 (SRC-3) is a transcriptional coactivator that interacts with nuclear receptors and some other transcription factors to enhance their effects on target gene transcription. We reported previously that SRC-3-deficient (SRC-3-/-) mice are extremely susceptible to Escherichia coli-induced septic peritonitis as a result of uncontrolled inflammation and a defect in bacterial clearance. In this study, we observed significant upregulation of SRC-3 in colonic epithelial cells in response to Citrobacter rodentium infection. Based on these findings, we hypothesized that SRC-3 is involved in host defense against attaching and effacing bacterial infection. We compared the responses of SRC-3-/- and wild-type mice to intestinal C. rodentium infection. We found that SRC-3-/- mice exhibited delayed clearance of C. rodentium and more severe tissue pathology after oral infection with C. rodentium compared with wild-type mice. SRC-3-/- mice expressed normal antimicrobial peptides in the colons but exhibited delayed recruitment of neutrophils into the colonic mucosa. Accordingly, SRC-3-/- mice showed a delayed induction of CXCL2 and CXCL5 in colonic epithelial cells, which are responsible for neutrophil recruitment. At the molecular level, we found that SRC-3 can activate the NF-kB signaling pathway to promote CXCL2 expression at the transcriptional level. Collectively, we show that SRC-3 contributes to host defense against enteric bacteria, at least in part via upregulating CXCL2 expression to recruit neutrophils. [ABSTRACT FROM AUTHOR]

Background: Rectal indometacin decreases the occurrence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). However, the population most at risk and the optimal timing of administration require further investigation. We aimed to assess whether pre-procedural administration of rectal indometacin in all patients is more effective than post-procedural use in only high-risk patients to prevent post-ERCP pancreatitis.Methods: We did a multicentre, single-blinded, randomised controlled trial at six centres in China. Eligible patients with native papilla undergoing ERCP were randomly assigned in a 1:1 ratio (with a computer-generated list) to universal pre-procedural indometacin or post-procedural indometacin in only high-risk patients, with stratification by trial centres and block size of ten. In the universal indometacin group, all patients received a single dose (100 mg) of rectal indometacin within 30 min before ERCP. In the risk-stratified, post-procedural indometacin group, only patients at predicted high risk received rectal indometacin, immediately after ERCP. Investigators, but not patients, were masked to group allocation. The primary outcome was overall ocurrence of post-ERCP pancreatitis. The analysis followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT02002650.Findings: Between Dec 15, 2013, and Sept 21, 2015, 2600 patients were randomly assigned to universal, pre-procedural indometacin (n=1297) or risk-stratified, post-procedural indometacin (n=1303). Overall, post-ERCP pancreatitis occurred in 47 (4%) of 1297 patients assigned to universal indometacin and 100 (8%) of 1303 patients assigned to risk-stratified indometacin (relative risk 0·47; 95% CI 0·34-0·66; p<0·0001). Post-ERCP pancreatitis occurred in 18 (6%) of 305 high-risk patients in the universal group and 35 (12%) of 281 high-risk patients in the risk-stratified group (p=0·0057). Post-ERCP pancreatitis was also less frequent in average-risk patients in the universal group (3% [29/992]), in which they received indometacin, than in the risk-stratified group (6% [65/1022]), in which they did not receive the drug (p=0·0003). Other than pancreatitis, adverse events occurred in 41 (3%; two severe) patients in the universal indometacin group and 48 (4%; one severe) patients in the risk-stratified group. The most common adverse events were biliary infection (22 [2%] patients vs 33 [3%] patients) and gastrointestinal bleeding (13 [1%] vs ten [1%]).Interpretation: Compared with a risk-stratified, post-procedural strategy, pre-procedural administration of rectal indometacin in unselected patients reduced the overall occurrence of post-ERCP pancreatitis without increasing risk of bleeding. Our results favour the routine use of rectal indometacin in patients without contraindications before ERCP.Funding: National Key Technology R&D Program, National Natural Science Foundation of China. [ABSTRACT FROM AUTHOR]

Context • In the October 2014 issue of the Journal of the American Medical Association (JAMA), Hinman et al published the results of an Australian clinical trial on acupuncture in a paper entitled “Acupuncture for Chronic Knee Pain: A Randomized Clinical Trial” (JAMA report), in which they concluded that neither acupuncture nor laser acupuncture had any greater effects than sham laser acupuncture for pain or function for patients aged 50 y and older with moderate-to-severe knee pain. That study has been criticized extensively by international scholars for its validity because serious methodological flaws existed throughout the study’s design, implementation, and conclusions. Objective • The current study intended to re-examine the prior study’s conclusions about the efficacy of acupuncture for chronic knee pain. Design • The current research team performed a reanalysis of relevant data from the JAMA report. Intervention • The original study included 4 groups: (1) an acupuncture group, which received needle acupuncture, inferred by the current authors to have been set up to be a positive control in the original study; (2) a laser acupuncture group, which received laser acupuncture; (3) a sham laser acupuncture group, which received sham laser acupuncture and acted as the negative controls for the laser acupuncture intervention; and (4) a control group, which received conventional care but no acupuncture or laser treatments. The study lasted 12 wk. Outcome Measures • The measures included evaluations in the following areas: (1) poststudy modifications—an evaluation of the consistency of the JAMA report with the study’s intentions as identified for a grant that was originally approved and funded by the Australian National Health and Medical Research Council (NHMRC) in 2009, as indicated in the study’s trial registration, and as compared with the published protocols and to the study’s originally stated objectives; (2) high heterogeneity—an assessment of the heterogeneity among the 4 groups for the overall outcome related to pain; (3) ineffectiveness of laser acupuncture—an analysis of laser acupuncture’s efficacy for chronic knee pain as stated in the JAMA report, using effect size (ES); (4) effectiveness of acupuncture—a reanalysis of acupuncture’s efficacy for chronic knee pain in comparison with the original analysis in the JAMA report, using ES; and (5) acupuncture after data adjustment—a new analysis of acupuncture’s efficacy for chronic knee pain using data from the original study that was discussed in the JAMA report, using ES, with an estimation after data adjustment and elimination of the dilution effect of the Zelen design. Results • Contrary to a general impression that acupuncture was the focus, laser acupuncture was the primary intervention tested in the actual study, “Laser Acupuncture in Patients With Chronic Knee Pain: A Randomized, Placebo Controlled Trial.” The study discussed in the JAMA report was neither a truly randomized, controlled trial (RCT) for acupuncture nor was it an appropriately designed, randomized study in general. High heterogeneity was found among its groups in the evaluation of overall pain in patients. Both the ES of 0.60 that had been set by Hinman et al for the minimal clinically important difference (MCID) and the resulting interpretation of results in the JAMA report were not appropriate. Using the original study’s criteria of efficacy, the reanalysis has confirmed that the laser acupuncture was not effective, whereas the acupuncture was found to be moderately effective for chronic knee pain (P < .05) for both overall pain and function at 12 wk, with an ES of 0.58, or after the adjustment of the data, with an ES of 0.67. Conclusions • The JAMA study was neither a conventional RCT nor an appropriately randomized trial, and its results are probably invalid. The ES of 0.60 for the MCID that was used in the JAMA study and the resulting explanation were not appropriate. Even with an ES of 0.60 for the MCID, acupuncture remained effective after data adjustment. Consequently, compared with conventional care, acupuncture treatment was found to be moderately effective for chronic knee pain in patients aged 50 y and older. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective study.Objective: The aim of this study was to detect risk factors for Adding-on after posterior correction surgery in patients with Lenke 1 or 2 AIS, and to explore whether Adding-on Index could be used to predict Adding-on effectively.Summary Of Background Data: Adding-on phenomenon is a common complication in Lenke 1 or 2 AIS patients after correction surgery. However, whether it can be predicted after surgery remains unknown.Methods: Lenke 1 or 2 AIS patients receiving correction surgery in our center from January 2009 to July 2013 were analyzed. Antero-posterior and lateral films were evaluated before surgery, at 2 weeks' and 2 years' follow-up. Patients were divided into 2 groups according to whether Adding-on occurred at the 2 years' follow-up. Risk factors of Adding-on were analyzed, and Adding-on Index was proposed and verified.Results: Sixteen patients (16.3%) suffered from distal Adding-on at 2-year follow-up. Several parameters were found to be significantly different between 2 groups, including Risser's sign, postoperative Cobb angle of main thoracic, postoperative Cobb angle of main thoracic curve at 2-year follow-up, preoperative and postoperative Cobb angle of lumbar curve, postoperative Cobb angle of lumbar curve at 2-year follow-up, LIV-EV, LIV-SV, LIV-CSVL, LAV-CSVL, LAV-LIV, DnfS, and postoperative TJK. No significant differences in SRS-22 scores were observed. Binary logistic regression analysis showed that DnfS and postoperative residual Cobb angle of lumbar curve were primary factors for occurrence of Adding-on. According to the regression equation, Adding-on Index was defined as 4 × DnfS-postoperative lumbar curves Cobb angle. On the basis of ROC curve, if Adding-on Index was more than 12, the occurrence rate of Adding-on was 88%. On the contrary, the rate of no Adding-on phenomenon was 80%.Conclusion: DnfS and posterior Cobb angle of lumbar curve were 2 important factors for Adding-on in Lenke 1, 2 AIS patients. Adding-on Index can be used to predict the occurrence of Adding-on effectively.Level Of Evidence: 4. [ABSTRACT FROM AUTHOR]

Bone marrow mesenchymal stem cells (BMMSCs) exert immunosuppressive activity in transplantation, and heme oxygenase-1 (HO-1) enhances their immunomodulatory effects. The aim of this study was to determine whether HO-1-transduced BMMSCs (HO-1/MSCs) improve rat liver transplantation (LTx) outcomes. Orthotopic LTx rejection models were treated with HO-1/MSCs, BMMSCs, HO-1, or normal saline, respectively. Our results showed a significant improvement in survival rates in the HO-1/BMMSCs group compared to the control groups. At all time points, liver function marker levels in the HO-1/MSCs group were significantly lower than in the other three groups; on POD 1, 7, and 14, the degree of rejection and apoptotic cells was significantly less in the HO-1/MSCs group than in the other three groups. Interleukin- (IL-) 10 and transforming growth factor-β levels were significantly increased, while IL-2, IL-6, IL-17, IL-23, tumor necrosis factor-α, and interferon-γ levels were significantly decreased in the HO-1/MSCs group when compared to the other groups. Splenocyte Tregs were significantly increased by HO-1/MSCs compared with controls on POD 3, 5, 7, 10, 14, and 28. Summarily, we provide evidence that HO-1/MSCs improved allogeneic LTx outcomes by attenuating inflammatory responses and acute cellular rejection, as well as enhanced immunomodulatory effects compared with BMMSCs. [ABSTRACT FROM AUTHOR]

Objective: To clarify the full range of benefits and adverse consequences of Helicobacter pylori eradication as a strategy for gastric cancer prevention, the community-based intervention trial was launched in Linqu County, China. Design: A total of 184 786 residents aged 25-54 years were enrolled in this trial and received 13C-urea breath test. H. pylori positive participants were assigned into two groups, either receiving a 10-day quadruple anti- H. pylori treatment or lookalike placebos together with a single dosage of omeprazole and bismuth. Results: The prevalence of H. pylori in trial participants was 57.6%. A total of 94 101 subjects completed the treatment. The overall H. pylori eradication rate was 72.9% in the active group. Gender, body mass index, history of stomach disease, baseline delta over baselinevalue of 13C-urea breath test, missed medication doses, smoking and drinking were independent predictors of eradication failure. The missed doses and high baseline delta over baseline-value were important contributors in men and women (all Ptrend<0.001). However, a doseresponse relationship between failure rate and smoking or drinking index was found in men (all Ptrend<0.001), while high body mass index (Ptrend<0.001) and history of stomach disease were significant predictors in women. The treatment failure rate increased up to 48.8% (OR 2.87, 95% CI 2.24 to 3.68) in men and 39.4% (OR 2.67, 95% CI 1.61 to 4.42) in women with multiple factors combined. Conclusions: This large community-based intervention trial to eradicate H. pylori is feasible and acceptable. The findings of this trial lead to a distinct evaluation of factors influencing eradication that should be generally considered for future eradication therapies. [ABSTRACT FROM AUTHOR]

Background: Sensitive assays are needed for detection of residual human immunodeficiency virus (HIV) in patients with undetectable plasma viral loads to determine whether eradication strategies are effective. The gold standard quantitative viral outgrowth assay (QVOA) underestimates the magnitude of the viral reservoir. We sought to determine whether xenograft of leukocytes from HIV type 1 (HIV)-infected patients with undetectable plasma viral loads into immunocompromised mice would result in viral amplification.Methods: Peripheral blood mononuclear cells or purified CD4(+) T cells from HIV or simian immunodeficiency virus (SIV)-infected subjects with undetectable plasma viral loads were adoptively transferred into NOD.Cg-Prkdc(scid)Il2rg(tm1Wjl)/SzJ (NSG) mice. The mice were monitored for viremia following depletion of human CD8(+) T cells to minimize antiviral activity. In some cases, humanized mice were also treated with activating anti-CD3 antibody.Results: With this murine viral outgrowth assay (MVOA), we successfully amplified replication-competent HIV or SIV from all subjects tested, including 5 HIV-positive patients receiving suppressive antiretroviral therapy (ART) and 6 elite controllers or suppressors who were maintaining undetectable viral loads without ART, including an elite suppressor from whom we were unable to recover virus by QVOA.Conclusions: Our results suggest that the MVOA has the potential to serve as a powerful tool to identify residual HIV in patients with undetectable viral loads. [ABSTRACT FROM AUTHOR]

Background: Bioartificial liver support system (BALSS) based on culturing hepatocytes is an important research field for the treatment of acute liver failure. It is necessary to monitor the state of liver cell functions during the treatment of BALSS in order to guide clinical treatment.Objective: To design a micro-channel chip to achieve flash mixing for timely detection of liver cell status in bioreactors and improving liver cells growth environment to ensure the efficacy of the bio-artificial liver support system.Methods: Alanine aminotransferase (ALT) and Urea are chosen as detection indicators to reflect the degree of liver cell injury and the detoxification function. A diamond tandem structure micro-channel is designed and optimized to achieve the efficient mixing of serum and ALT or Urea reagent.Results: The simulation and experimental results show that the diamond tandem structure micro-channel can significantly improve the mixing efficiency and meet the online detecting requirements.Conclusion: The easily controllable diamond tandem structure micro-channel combines the advantages of active and passive mixer and can effectively mix the serum and ALT or Urea reagent. It lays the foundation for online monitoring of liver cells and will help to improve the viability of liver cell in the bioreactor. [ABSTRACT FROM AUTHOR]

Increased expression of the cytokine interferon (IFN)-γ plays a pivotal role in vitiligo-induced depigmentation. However, the major source of IFN-γ in vitiligo patients and the mechanisms underlying melanocyte destruction are unknown. In this study, a large number of skin infiltrating IFN-γ+ cells and CD8+ T cells were detected in progressive vitiligo. Among the peripheral blood mononuclear cells (PBMCs) of vitiligo patients, CD8+ cytotoxic T lymphocytes (CTLs) that express IFN-γ exhibited significant expansion, which suggests that activated CTLs are the main source of increased IFN-γ in progressive vitiligo. An in vitro analysis demonstrated that IFN-γ inhibits melanogenesis in primary cultured human melanocytes by altering melanogenic enzyme mRNA expression and, more importantly, that IFN-γ directly induces melanocyte apoptosis. Our data indicate that vitiligo pathophysiology may be linked to globally activated CD8+ CTL subpopulations, which produce increased IFN-γ and induce melanocyte dysfunction and apoptosis. [ABSTRACT FROM AUTHOR]

Study Design. Bioinformatics analysis of published microarray data. Objective. This study aimed to reveal the possible genes and pathways related to the pathogenesis of disc degeneration (DD) by analyzing the microarray data. Summary of Background Data. DD is one of the main causes of low back pain, which has become an enormous economic burden for society. Methods. Gene expression data of annulus cells and nucleus pulposus cells from patients with DD and controls subjects were downloaded from Gene Expression Omnibus. T test and enrichment analysis were used to identify differentially expressed genes (DEGs) and DEGs-associated functions and pathways in DD, respectively. Protein-protein interaction network and module were constructed to analyze the key nodes associated with this disease. Results. A total of 326 DEGs and 35 DEGs were obtained from the annulus cells and nucleus pulposus cells, respectively. The DEGs of DD in annulus cells were mainly involved in translation, cell adhesion, cell death regulation, and skeletal system development whereas the DEGs in nucleus pulposus cells were mainly related to the biological processes of vascular system development, skeletal system development, and enzyme-linked receptor protein signaling pathway. COL3A1 was the common DEG in both annulus cells and nucleus pulposus cells. The genes encode ribosomal proteins (RPL8, RPS16, and RPS23) in module were enriched in biological processes of translation, translation elongation, and RNA processing. Conclusion. The results revealed the involvement of COL3A1 in skeletal system process and RPL8, RPS16, and RPS23 in the protein synthesis processes in the progression of DD, suggesting their potential use in the diagnosis and therapy of DD. [ABSTRACT FROM AUTHOR]

We investigated the possiblepathogenic role of a microRNA (miR-155) in primary immune thrombocytopenia (ITP). We used quantitative real-time PCR to determine the relative expression of miR-155 and SOCS1 (suppressor of cytokine signaling) mRNA in peripheral blood mononuclear cells (PBMCs) from 28 ITP patients and 28 healthy controls. Cytokine plasma levels were determined by ELISA. Possible associations between miR-155 levels and serum cytokine concentrations were assessed using Spearman or Pearson correlation analysis. Seven naive ITP patients were followed and the effects of medical treatment on miR-155 levels were assessed. Compared to healthy controls, ITP patients had increased miR-155 and decreased SOCS1 mRNA levels. ITP patients also had increased plasma IL-17A and decreased IL-4, IL-10 and TGF-β1 levels. miR-155 levels were negatively correlated with platelet counts, SOCS1 mRNA levels, and the plasma levels of IL-4, IL-10 and TGF-β1, but positively correlated with plasma IL-17A levels. Medical treatment for ITP decreased miR-155 levels. Thus, our results suggest that miR-155 might be involved in the pathogenesis of ITP by regulating cytokine profiles, which may be mediated by miR-155 targeting SOCS1. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Candida albicans is considered to be an obligate diploid fungus. Here, we describe an approach to isolate aneuploids or haploids induced by the short-term (12–16 h) exposure of diploid reference strains SC5314 and CAI4 to the most commonly used antifungal drug, fluconazole, followed by repeated single-cell separation among small morphologically distinct colonies in the inhibition zone. The isolated strains had altered cell morphology and LOH events in the MTL and other marker alleles of the analyzed loci at 8 chromosomes of C. albicans with decreased DNA content. The present study employed next-generation sequencing (NGS) combined flow cytometry analysis of the DNA content to analyze the haploid, autodiploid, and aneuploid strains that arose from the fluconazole treatment instead of using the conventional single nucleotide polymorphism/comparative genome hybridization (SNP/CGH) method. A multiple-alignment tool was also developed based on sequenced data from NGS to establish haplotype mapping for each chromosome of the selected strains. These findings revealed that C. albicans experiences ‘concerted chromosome loss’ to form strains with homozygous alleles and that it even has a haploid status after short-term exposure to fluconazole. Additionally, we developed a new platform to analyze chromosome copy number using NGS. [ABSTRACT FROM AUTHOR]

The present study identified prognostic factors for successful varicocelectomy for the treatment of varicocele-induced male infertility. All varicoceles were diagnosed and graded by physical examination and ultrasound. Pre- and postoperative analysis of semen specimens measured sperm density, morphology and motility. 'Responder' and 'non-responder' status was determined by semen analyses at 3, 6 and 12 months postoperatively. Varicocele Grades 1, 2 and 3 were found in 16, 36 and 28 patients, respectively; 49 patients (61.3%) were responders based on improved seminograms. Significant postoperative increases were noted in sperm density (from 18.20 ± 14.76 x 106 to 32.36 ± 24.81 x 106 mL-1; P < 0.001), sperm morphology (from 57.21 ± 17.35% to 62.66 ± 15.18%; P = 0.006) and percentage motility (from 29.89 ± 14.71% to 50.92 ± 19.30%; P < 0.001). Multivariate logistic regression indicated that age (odds ratio (OR) 0.56; P < 0.001) and preoperative sperm density (OR 1.22; P = 0.001) had significant unfavourable and favourable associations, respectively, with the likelihood of successful varicocelectomy. Furthermore, a preoperative sperm density of 12 x 106 mL-1 as a cut-off point was able to predict successful varicocelectomy with a sensitivity of 77.6% and specificity of 77.4% (area under the curve = 0.85; P < 0.001; 95% confidence interval 0.76-0.92). Age and preoperative sperm density are prognostic factors for successful varicocelectomy. The results of the present study may allow clinicians to predict surgical improvement in fertility in patients with varicocele. Controversy exists in determining the extent of negative impact of varicocele on male fertility and the value of varicocele surgery in correcting infertility. The study aimed to identify predictive factors of successful varicocele surgery for treating male infertility induced by varicocele, and found that age and preoperative sperm density are the predictive factors. Our results may allow clinicians to predict surgical improvement in fertility of male patients with varicocele. [ABSTRACT FROM AUTHOR]

Recent studies have shown that the tonicity-responsive enhancer binding protein (TonEBP)/vascular endothelial growth factor-C (VEGF-C) signaling pathway-induced lymphangiogenesis provides a buffering mechanism for high salt (HS) intake-induced elevation of blood pressure (BP). Moreover, blocking of TonEBP/VEGF-C signaling by mononuclear phagocyte depletion can induce salt-sensitive hypertension in rats. We hypothesized that HS intake could have an impact on cardiac lymphangiogenesis, and regulation of VEGF-C bioactivity, which is largely through the main receptor for VEGFR-3, may modulate HS intake-induced left ventricular remodeling. We demonstrated upregulation of TonEBP, increased macrophage infiltration, and enhanced lymphangiogenesis in the left ventricles of spontaneously hypertensive rats (SHR) that were fed a HS diet (8.0% NaCl). Then, retrovirus vectors capable of overexpression (△N△C/VEGF-C/Cys152Ser, used for overexpressing VEGF-C) and blocking (VEGFR-3-Rg, used for trapping of bioactive VEGF-C) of VEGF-C and control vector (pLPCX) were intravenously administered to SHR from week 9 of a 12-wk HS loading period. At the end of the HS challenge, overexpression of VEGF-C led to enhanced cardiac lymphangiogenesis, decreased myocardial fibrosis, and macrophage infiltration, preserved left ventricular functions, as well as decreased blood pressure level compared with the HS group and the control vector-treated HS group. In contrast, systemic blocking of VEGF-C was associated with elevation of blood pressure level and an exacerbation of hypertensive left ventricular remodeling, as indicated by increased fibrosis and macrophage infiltration, and diminished lymphangiogenesis. Hence, our findings highlight that VEGF-C/VEGFR-3 is a promising therapeutic target to attenuate hypertensive left ventricular remodeling induced by HS intake, presumably via blood pressure-dependent and -independent mechanisms. [ABSTRACT FROM AUTHOR]

Introduction. Hepatic inflammation underlies the pathogenesis of chronic diseases such as insulin resistance and type 2 diabetes mellitus. S- [6] -Gingerol has been shown to have anti-inflammatory properties. Important inflammatory mediators of interleukins include nuclear factor kB (NFkB) and cyclo oxygenase 2 (COX2). We now explore the mechanism of anti-inflammatory effects of S-[6]-gingerol in liver cells. Methods. HuH7 cells were stimulated with ILβ to establish an in vitro hepatic inflammatory model. Results. S- [6] -Gingerol attenuated ILlβ-induced inflammation and oxidative stress in HuH7 cells, as evidenced by decreasing mRNA levels of inflammatory factor IL6, IL8, and SAAI, suppression of ROS generation, and increasing mRNA levels of DHCR24. In addition, S- [6] -gingerol reduced ILβ-induced COX2 upregulation as well as NF/cB activity. Similar to the protective effects of S-[6] -gingerol, both NS-398 (a selective COX2 inhibitor) and PDTC (a selective NF/cB inhibitor) suppressed mRNA levels of IL6, IL8, andSAAl. Importantly, PDTC attenuated ILlβ-induced overexpression of COX2. Of particular note, the protective effect of S- [6]-gingerol against the ILlβ-induced inflammatory response was similar to that of BHT, an ROS scavenger. Conclusions. The findings of this study demonstrate that S- [6] -gingerol protects HuH7 cells against ILlβ-induced inflammatory insults through inhibition of the ROS/NFκB/COX2 pathway. [ABSTRACT FROM AUTHOR]

Calcium signals in hepatocytes control cell growth, proliferation, and death. Members of the transient receptor potential (TRP) cation channel superfamily are candidate calcium influx channels. NFκB activation strictly depends on calcium influx and often induces antiapoptotic genes favouring cell survival. Previously, we reported that S-[6]-gingerol is an efficacious agonist of the transient receptor potential cation channel subfamily V member 1 (TRPV1) in neurones. In this study, we tested the effect of S-[6] -gingerol on HuH-7 cells using the Fluo-4 calcium assay, RT-qPCR, transient cell transfection, and luciferase measurements. We found that S- [6] -gingerol induced a transient rise in [Ca2+]i in HuH-7 cells. The increase in [Ca2+]i induced by S-[6]-gingerol was abolished by preincubation with EGTA and was also inhibited by the TRPV1 channel antagonist capsazepine. Expression of TRPV1 in HuH-7 cells was confirmed by mRNA analysis as well as a test for increase of [Ca2+]i by TRPV1 agonist capsaicin and its inhibition by capsazepine. We found that S- [6] -gingerol induced rapid NFκB activation through TRPV1 in HuH-7 cells. Furthermore, S- [6] -gingerol-induced NFκB activation was dependent on the calcium gradient and TRPV1. The rapid NFκB activation by S- [6] -gingerol was associated with an increase in mRNA levels of NFκB-target genes: cIAP-2, XIAP, and Bcl-2 that encode antiapoptotic proteins. [ABSTRACT FROM AUTHOR]

Background: Esophageal Squamous Cell Carcinoma (ESCC) is a major subtype of esophageal cancer causing significant morbility and mortality in Asia. Mechanism of initiation and progression of this disease is unclear. Tumor initiating cells (TICs) are the subpopulation of cells which have the ability to self-renew, as well as, to drive initiation and progression of cancer. Increasing evidence has shown that TICs exist in a variety of tumors. However, the identification and characterization of TICs in esophageal carcinoma has remained elusive. Methodology/Principal Findings: to identify TICs in ESCC, ESCC cell lines including two primary cells were used for screening suitable surface marker. Then colony formation assay, drug resistant assay and tumorigenicity assay in immune deficient mice were used to characterize TICs in ESCC. We found that just the CD44 expression correlated with tumorigenicity in ESCC cell lines. And then induced differentiation of ESCC cells by all-trans retinoic acid treatment led to decreased expression of CD44. The FACS isolated cell subpopulations with high CD44 expression showed increased colony formation and drug resistance in vitro, as well as significantly enhanced tumorigenicity in NOD/SICD mice, as compared to the low expressing CD44 ESCC cells. Conclusions/Significance: our study has discovered a novel TIC surface marker, CD44, which can be utilized to enrich efficiently the TICs in ESCC. These findings will be useful for further studies of these cells and exploring therapeutic approaches. [ABSTRACT FROM AUTHOR]

TH17 cells have been implicated in a growing list of inflammatory disorders. Antagonism of TH17 cells can be used for the treatment of inflammatory injury. Currently, very little is known about the natural compound controlling the differentiation of TH17 cells. Here, we showed that Baicalin, a compound isolated from a Chinese herb, inhibited TH17 cell differentiation both in vitro and in vivo. Baicalin might inhibit newly generated TH17 cells via reducing RORct expression, and together with up-regulating Foxp3 expression to suppress RORct-mediated IL-17 expression in established TH17 cells. In vivo treatment with Baicalin could inhibit TH17 cell differentiation, restrain TH17 cells infiltration into kidney, and protect MRL/lpr mice against nephritis. Our findings not only demonstrate that Baicalin could control TH17 cell differentiation but also suggest that Baicalin might be a promising therapeutic agent for the treatment of TH17 cells-mediated inflammatory diseases. [ABSTRACT FROM AUTHOR]

NSCs (neural stem cells) provide a powerful research tool for the design and discovery of new approaches to cell replacement therapy during brain repair. However, the usefulness of this tool has been particulaly obstructed by limited neuronal differentiation of NSCs. Brn-4, a member of the POU domain family of transcription factors, has been previously implicated in the development of neurons by expression analysis. Here, we directly investigated the effects of Brn-4 on the neuronal differentiation and development of NSCs derived from the E13 rat midbrain. We found that Brn-4 knockdown in NSCs resulted in a significant decrease of MAP-2-positive neurons with immature morphology. Overexpression of Brn-4 in NSCs markedly increased the production and maturation of newborn neurons. These results suggest that Brn-4 has a critical role in the neuronal differentiation of mesencephalic NSCs and the maturation of newborn neurons. Brn-4 may be utilized to manipulate NSCs for gene and cell therapy of several neurological diseases. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the molecular epidemiology and OXA-type carbapenemase genes of 83 imipenem-resistant Acinetobacter spp. collected from 2 university hospitals (hospitals A and B) and a regional hospital (hospital C) during 2007 in Taiwan. Genotyping by pulsed-field gel electrophoresis identified 51 pulsotypes. None of the pulsotypes established predominance throughout the 3 hospitals. Multiplex polymerase chain reaction of blaOXA genes showed that 100% (18/18), 91%(31/34), and 100% (31/31) of the Acinetobacter spp. collected from hospital A, B, and C, respectively, possessed blaOXA-51–like genes. None of the strains carrying blaOXA-23–like and blaOXA-24–like genes were found in hospital A. The coexistences of blaOXA-51–like/blaOXA-23–like and blaOXA-51–like/blaOXA-24–like genes detected in hospitals B and C were 26% (9/34) and 12% (4/34) and 58% (18/31) and 3% (1/31), respectively. Among blaOXA-23–like gene-carrying isolates collected from hospitals, clonal spread of strains carrying the blaOXA-23 gene was detected in the regional hospital but not the other 2 university hospitals. The results suggest that interhospital dissemination of imipenem-resistant Acinetobacter spp. was not found in these hospitals. The increasing percentage of OXA-23 in OXA-type carbapenemases in Acinetobacter spp. from the regional hospitals to medical centers deserves further attention in Taiwan. [Copyright &y& Elsevier]

Objective: To exclude possible psychological effects of qigong therapy in the treatment of addiction effectively, morphine-dependence models need to be established in mice and rats. Method: The effects of external qi on withdrawal syndrome were examined in naloxone-precipitated mice and rats in three randomized control experiments: naloxone-precipitated test in morphine-dependent mice (n = 100 in 5 groups, 20 mice each group); conditioned position preference test in morphine-abstinent mice (n = 30 for 3 groups, 10 each); and naloxone-precipitated test with paired box in morphine-dependent rats (n = 40 for 4 groups, 10 each). Results: These experiments showed that morphine-dependent mice, after external qigong (EQ) therapy, had decreased incidence of jumping and lower jumping frequencies, and attenuated loss of body weight. After EQ therapy, morphine-dependent rats had reduced withdrawal scores and body weight loss was inhibited. In the conditioned place preference test, the time spent in the drug-paired box was significantly shorter for the qigong group than for the morphine group. Conclusion: These results suggest that qigong might have an inhibitory effect on withdrawal syndrome, and reduce the dependence potential in mice. Three different designs confirm that the impact of qigong therapy on morphine-abstinent mice and rats is reliable and substantial. Further research on the effectiveness and the mechanism of qigong therapy on addiction is warranted. [ABSTRACT FROM AUTHOR]