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The NLRP3 inflammasome plays a critical role in mediating the innate immune defense against pathogenic infections, but aberrant activation of NLRP3 inflammasome has been linked to a variety of inflammatory diseases. Thus targeting the NLRP3 inflammasome represents a promising therapeutic for the treatment of such diseases. Scutellarin is a flavonoid isolated from Erigeron breviscapus (Vant.) Hand.-Mazz. and has been reported to exhibit potent anti-inflammatory activities, but the underlying mechanism is only partly understood. In this study, we aimed to investigate whether scutellarin could affect the activation of NLRP3 inflammasome in macrophages. The results showed that scutellarin dose-dependently reduced caspase-1 activation and decreased mature interleukin-1β (IL-1β) release in lipopolysaccharide (LPS)-primed macrophages upon ATP or nigericin stimulation, indicating that scutellarin inhibited NLRP3 inflammasome activation in macrophages. Consistent with this, scutellarin also suppressed pyroptotic cell death in LPS-primed macrophages treated with ATP or nigericin. ATP or nigericin-induced ASC speck formation and its oligomerization were blocked by scutellarin pre-treatment. Intriguingly, scutellarin augmented PKA-specific phosphorylation of NLRP3 in LPS-primed macrophages, which was completely blocked by selective PKA inhibitor H89, suggesting that PKA signaling had been involved in the action of scutellarin to suppress NLRP3 inflammasome activation. Supporting this, the inhibitory effect of scutellarin on NLRP3 inflammasome activation was completely counteracted by H89 or adenyl cyclase inhibitor MDL12330A. As NLRP3-dependent release of IL-1β has a critical role in sepsis, the in vivo activity of scutellarin was assayed in a mouse model of bacterial sepsis, which was established by intraperitoneally injection of a lethal dose of viable Escherichia coli . Oral administration of scutellarin significantly improved the survival of mice with bacterial sepsis. In line with this, scutellarin treatment significantly reduced serum IL-1β levels and attenuated the infiltration of inflammatory cells in the liver of E. coli -infected mice. These data indicated that scutellarin suppressed NLRP3 inflammasome activation in macrophages by augmenting PKA signaling, highlighting its potential therapeutic application for treating NLRP3-related inflammatory diseases.

Objective: To compare the safety and immunogenicity of two different sequential schedules of inactivated poliomyelitis vaccine made from Sabin strain (sIPV) followed by typeⅠ+Ⅲ bivalent oral poliovirus vaccine (bOPV) in Drug Candy (DC) form or liquid dosage form). Methods: This randomized, blinded, single center, parallel-group controlled trial was done from September 2015 to June 2016 in Liuzhou, Guangxi province. Healthy infants aged ≥2 months were eligible for enrollment and divided into 1sIPV+2bOPV or 2sIPV+1bOPV sequential schedules. According to the bOPV dosage form each sequential schedules, the subjects again were divided into drug candy(DC) form or liquid dosage form group, being 1sIPV+bOPV (DC)/1sIPV+2bOPV(liquid)/2sIPV+1bOPV(DC)/2sIPV+1bOPV(liquid). According to 0, 28, 56 d immunization schedule, Each group were given 3 doses. We recorded adverse events during the clinical trial (399 participants who receive at least one dose). 28 days post-Dose 3, we receive a total of 350 blood samples (excluding the quitters or subjects against trial plan), using cell culture trace against polio virus neutralization test Ⅰ, Ⅱ, Ⅲ neutralizing antibody (GMT), calculating the antibody positive rate.PolioⅠ,Ⅱand Ⅲ antibody titers were assessed by virus-neutralizing antibody assay and the seroconversion (4-fold increase in titer) from pre-Dose 1 to 28 days post-Dose 3 was calculated (total 350 samples) . Results: During the vaccination, the incidence of AEs in 1sIPV+2bOPV(DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV(DC), 2sIPV+1bOPV (liquid) group were 79%, 76%, 80% and 74% (χ(2)=1.23, P= 0.747) , respectively. The severe AEs in groups were 6%, 5%, 6% and 4% (χ(2)=0.57, P= 0.903) , respectively, and none was considered to be vaccination related. 28 days after 3(rd) vaccination, the seroconversion rates in 1sIPV+2bOPV (DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV (DC), 2sIPV+1bOPV (liquid) group, were 99%, 100%, 99% and 99% (χ(2)=0.94, P= 0.815) , respectively, for type Ⅰ poliovirus; and 47%, 57%, 80%, 79% (χ(2)=31.56, P< 0.001) , respectively, for type Ⅱ; and were 100%, 99%, 100%, 99% (χ(2)=2.02, P= 0.568) , respectively, for type Ⅲ. In each group, the GMT of antibody against poliovirus typeⅠ were 4 539.68, 6 243.43, 6 819.53 and 7 916.29 ( F= 25.87, P< 0.001) , respectively; Type Ⅱ were 12.98, 10.54, 63.75 and 84.21 ( F= 8.68, P= 0.034) , respectively; Type Ⅲ were 1 172.55, 1 416.03, 2 648.89 and 3 250.75 ( F= 14.50, P= 0.002) , respectively. Conclusion: On the same sequential schedules, there was no significant difference between the dosage forms, all of them showed good safety and immunogenicity. In the same dosage forms with different sequential schedules, the seroconversion rate was higher in 2 dose sIPV group than the 1 dose sIPV group, especially at the neutralizing antibody GMT level against polio type Ⅱ and Ⅲ after vaccination.

CPT-11 is a first-line chemotherapeutic agent for the treatment of colorectal cancer in clinic. Previous studies including ours have demonstrated that CPT-11 is, however, toxic to the intestinal epithelium and resident peritoneal macrophages. By interacting with B1 cells, the resident peritoneal macrophages play critical roles in the maintenance of gastrointestinal homeostasis. It remains therefore elusive whether these peritoneal innate immune cells could be rebuilt spontaneously or artificially after being impaired by CPT-11 administration. In this study, we found that mouse resident peritoneal macrophages, namely the large peritoneal macrophages (LPMs) with a CD11b + F4/80 hi GATA6 + phenotype, and B1 (CD19 + CD23 - ) cells were depleted by intraperitoneal (i.p.) CPT-11 treatment within 1 week, but reappeared from day 14 after CPT-11 treatment. However, the recovery processes of these innate immune cells were slow, as their counts could not be fully recovered even 2 months later, when compared with that of vehicle-treated control group. Interestingly, in the peritoneal cavity of the mice treated with CPT-11, the cell counts of LPMs and B1 cells were significantly increased after adoptive transfer with syngeneic peritoneal exudate cells (PECs) from healthy mice. Adoptive transfer with bone marrow cells also slightly increased, although not significantly, the cell counts of LPMs and B1 cells in CPT-11-treated mice. The survival rate of bacterial infected mice was significantly reduced by i.p. CPT-11 treatment in comparison with vehicle-treated or untreated control groups. Besides, oral administration of CPT-11 also had a delayed toxicity on the resident peritoneal macrophages. Our results suggest that CPT-11 has prolonged deleterious effects on peritoneal innate immune cells but adoptive transfer with PECs may accelerate their recovery processes, highlighting the potential of adoptive cell transfer as an avenue to counteract the adverse effects of this chemotherapeutic agent.

Objective: To investigate the clinical features and genetic characteristics of cases with X-linked immunodeficiency with magnesium defect, Epstein-Barr virus (EBV) infection, and neoplasia (XMEN). Methods: Characteristics of clinical material, immunological data and gene mutation of two cases with XMEN in the same family in China were retrospectively analyzed. The related reports literature were searched by using search terms'MAGT1 gene'or'XMEN'. Results: The proband, a 2-year-eight-month old boy, was admitted due to 'Urine with deepened color for two days and yellow stained skin for one day'. He had suffered from recurrent upper respiratory tract infection and sinusitis previously. Hemoglobin level was 38 g/L. The absolute count of reticulocytes was 223.2×10(9)/L. Urobilinogen level was 38 μmol/L (3-16 μmol/L). Coomb's test was positive. Both total (77.2 μmol/L) and indirect bilirubin (66 μmol/L) levels were elevated. There was an inverted CD4(+)/CD8(+)T cell ratio (0.89). The gene sequencing results showed MAGT1 gene c.472delG, p.D158Mfs*6 mutation. His 1-year-6-month old brother, was also identified to have MAGT1 gene c.472delG, p.D158Mfs*6 mutation.The younger brother mainly suffered from recurrent upper respiratory tract infection, accompanied by an inverted CD4(+)/CD8(+)T cell ratio (0.45), an elevated ratio and number of total B cells (45.7%). A total of 7 reports were retrieved including 11 male cases caused by MAGT1 gene mutation. These 11 cases were characterized by EBV viremia (11 cases), recurrent upper respiratory tract infection, otitis media or sinusitis (10 cases), secondary neoplasia diseases (8 cases), reduction of CD4(+)/CD8(+) T cell ratio (7 cases),and autoimmune thrombocytopenia or hemolytic anemia (2 cases). Conclusion: XMEN often manifests as male onset, recurrent upper respiratory tract infection, otitis media or sinusitis, EBV viremia, lymphoproliferative disease or lymphoma, autoimmune diseases and reduction of CD4(+)/CD8 (+)T cell ratio. NKG2D expression in NK cells is significantly reduced, and gene sequencing analysis shows a pathogenic mutation in MAGT1 gene.

Introduction: The treatment of haemophilia varies across countries and across regions within some countries. Similar variation has been observed in health-related quality of life (HR-QoL). Relatively little is known about the HR-QoL of boys with haemophilia in China., Aim: The aim of this study was to describe the HR-QoL of boys with haemophilia in China using the Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT)., Methods: Boys (4-18 years of age) with haemophilia and their parents were enroled in a cross-sectional study. All parents/guardians of study subjects were requested to complete a CHO-KLAT questionnaire during a clinic visit, and report on several other clinical and socioeconomic factors in the past year. Boys who were > 7 years also completed the CHO-KLAT., Results: A total of 269 parents of boys with haemophilia, from 13 hospitals in 12 provinces, were enroled during 2014. The boys ranged from 4.0 to 17.9 years of age; 91% had haemophilia A, most had moderate (52%) or severe (36%) disease, and most were receiving sub-optimal on-demand therapy or low-dose prophylactic therapy. Child self-report CHO-KLAT scores were available for 171 boys ≥7 years of age and ranged from 24.2 to 85.3 with a mean of 57.6 (n = 171). Parent proxy-reported CHO-KLAT scores ranged from 25.0 to 88.7 with a mean of 55.1 (n = 269)., Conclusion: HR-QoL scores in boys with haemophilia in China were substantially lower than reported from Canadian and European boys with haemophilia. Longer term prospective studies are required to examine the factors impacting the HR-QoL for boys with haemophilia in China., (© 2017 John Wiley & Sons Ltd.)

Background/aims: Colonoscopy screening has been accepted broadly to evaluate the risk and incidence of colorectal cancer (CRC) during health examination in outpatients. However, the intrusiveness, complexity and discomfort of colonoscopy may limit its application and the compliance of patients. Thus, more reliable and convenient diagnostic methods are necessary for CRC screening. Genome instability, especially copy-number variation (CNV), is a hallmark of cancer and has been proved to have potential in clinical application., Methods: We determined the diagnostic potential of chromosomal CNV at the arm level by whole-genome sequencing of CRC plasma samples (n = 32) and healthy controls (n = 38). Arm level CNV was determined and the consistence of arm-level CNV between plasma and tissue was further analyzed. Two methods including regular z score and trained Support Vector Machine (SVM) classifier were applied for detection of colorectal cancer., Results: In plasma samples of CRC patients, the most frequent deletions were detected on chromosomes 6, 8p, 14q and 1p, and the most frequent amplifications occurred on chromosome 19, 5, 2, 9p and 20p. These arm-level alterations detected in plasma were also observed in tumor tissues. We showed that the specificity of regular z score analysis for the detection of colorectal cancer was 86.8% (33/38), whereas its sensitivity was only 56.3% (18/32). Applying a trained SVM classifier (n = 40 in trained group) as the standard to detect colorectal cancer relevance ratio in the test samples (n = 30), a sensitivity of 91.7% (11/12) and a specificity 88.9% (16/18) were finally reached. Furthermore, all five early CRC patients in stages I and II were successfully detected., Conclusion: Trained SVM classifier based on arm-level CNVs can be used as a promising method to screen early-stage CRC., (© 2018 The Author(s). Published by S. Karger AG, Basel.)

Background and Aim: The relationship between exposure to hepatitis B virus (HBV) and atherosclerosis-associated disease morbidity has not been clearly elucidated. We performed a meta-analysis to explore whether exposure to HBV is a risk factor for atherosclerosis-associated diseases., Methods: We searched the PubMed, Web of Science, Cochrane Library, Embase, and Scopus databases for related studies. We then chose the eligible studies for meta-analysis and assessed quality assessment and risk of bias., Results: The meta-analysis of the included studies showed that exposure to HBV tends to increase atherosclerosis-associated disease morbidity, but this increase was not statistically significant., Conclusions: Hepatitis B virus may not be a risk factor for atherosclerosis-associated diseases, but further studies that employ more sensitive clinical parameters are needed to verify this result.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with glucose intolerance, insulin resistance and type 2 diabetes mellitus (T2DM). Although several studies have revealed that intermittent hypoxia (IH) in OSAHS may further aggravate pancreatic β cell damage and promote the evolution of type 2 diabetes (T2DM) by increasing oxidative stress, the underlying mechanisms are unclear. Honokiol, a potent radical scavenger, has been demonstrated to ameliorate oxidative stress in many cases. The present study aimed to explore the potential mechanism of IH and diabetes synergistically damage and destruct the pancreatic β cell, examine the effects of honokiol on ameliorating pancreatic β cell injury in this context and explore the mechanism of such effects. High glucose (HG) cultured INS-1 cells were exposed to 50 μM of honokiol for 24, 48 and 72 h with or without IH intervention. T2DM rats were treated with honokiol and exposed to 80 s of IH followed by 160 s of normoxia for 8 weeks. The cell proliferation, apoptosis and oxidative stress were measured. Blood glucose, insulin, glucagon and HOMA-IR (Homeostasis model assessment -insulin resistence) were also detected, and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were detected by immunofluorescence staining and western blotting. Honokiol can reduce oxidative stress, cytotoxicity and apoptosis in the INS-1 cells of rats receiving HG treatment or both HG and IH treatment. IH can further aggravate pancreas dysfunction, cause a marked elevation in fasting blood glucose, glucagon, HOMA-IR and oxidative stress levels in DM rats. In addition, honokiol can effectively activate the Nrf2/ARE pathway and reverse this pancreatic dysfunction in vivo and in vitro. These findings indicate that honokiol acts as a potent ROS scavenger via Nrf2/ARE pathway and effectively attenuates oxidative stress and improves pancreatic β cell function of DM rats under IH treatment., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

The structural, electronic and magnetic properties of the (FeC) n (n = 1-8) clusters are studied using the unbiased CALYPSO structure search method and density functional theory. A combination of the PBE functional and 6-311 + G* basis set is used for determining global minima on potential energy surfaces of (FeC) n clusters. Relatively stabilities are analyzed via computing their binding energies, second order difference and HOMO-LUMO gaps. In addition, the origin of magnetic properties, spin density and density of states are discussed in detail, respectively. At last, based on the same computational method, the structures, magnetic properties and density of states are systemically investigated for the 3d (V, Cr, Mn and Co) atom doped (FeC) 8 cluster.

Background: Immune dysregulation has been linked to occlusive vascular remodeling in pulmonary arterial hypertension (PAH) that is hereditary, idiopathic, or associated with other conditions. Circulating autoantibodies, lung perivascular lymphoid tissue, and elevated cytokines have been related to PAH pathogenesis but without a clear understanding of how these abnormalities are initiated, perpetuated, and connected in the progression of disease. We therefore set out to identify specific target antigens in PAH lung immune complexes as a starting point toward resolving these issues to better inform future application of immunomodulatory therapies., Methods: Lung immune complexes were isolated and PAH target antigens were identified by liquid chromatography tandem mass spectrometry, confirmed by enzyme-linked immunosorbent assay, and localized by confocal microscopy. One PAH antigen linked to immunity and inflammation was pursued and a link to PAH pathophysiology was investigated by next-generation sequencing, functional studies in cultured monocytes and endothelial cells, and hemodynamic and lung studies in a rat., Results: SAM domain and HD domain-containing protein 1 (SAMHD1), an innate immune factor that suppresses HIV replication, was identified and confirmed as highly expressed in immune complexes from 16 hereditary and idiopathic PAH versus 12 control lungs. Elevated SAMHD1 was localized to endothelial cells, perivascular dendritic cells, and macrophages, and SAMHD1 antibodies were prevalent in tertiary lymphoid tissue. An unbiased screen using metagenomic sequencing related SAMHD1 to increased expression of human endogenous retrovirus K (HERV-K) in PAH versus control lungs (n=4). HERV-K envelope and deoxyuridine triphosphate nucleotidohydrolase mRNAs were elevated in PAH versus control lungs (n=10), and proteins were localized to macrophages. HERV-K deoxyuridine triphosphate nucleotidohydrolase induced SAMHD1 and proinflammatory cytokines (eg, interleukin 6, interleukin 1β, and tumor necrosis factor α) in circulating monocytes, pulmonary arterial endothelial cells, and also activated B cells. Vulnerability of pulmonary arterial endothelial cells (PAEC) to apoptosis was increased by HERV-K deoxyuridine triphosphate nucleotidohydrolase in an interleukin 6-independent manner. Furthermore, 3 weekly injections of HERV-K deoxyuridine triphosphate nucleotidohydrolase induced hemodynamic and vascular changes of pulmonary hypertension in rats (n=8) and elevated interleukin 6., Conclusions: Our study reveals that upregulation of the endogenous retrovirus HERV-K could both initiate and sustain activation of the immune system and cause vascular changes associated with PAH., (© 2017 American Heart Association, Inc.)

Natural products such as caffeine have been found to be effective in reducing body weight through lipolysis. Here, we report the successful loading of caffeine onto dissolving microneedle following inhibition of its crystal growth by hyaluronic acid (HA), the matrix material of the dissolving microneedle (DMN). Further, the anti-obesity activity of caffeine was evaluated in high-fat diet-induced obese C57BL/6J mice. After 6weeks of caffeine loaded dissolving microneedle patch (CMP) administration, lipolysis improved significantly as shown by leptin and adiponectin activity, which resulted in considerable weight loss of about 12.8±0.75% in high-fat diet-induced obese mice. Comparison of the levels of triglyceride, total cholesterol, high-density lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol after CMP administration with the initial levels in obese mice indicated significant anti-obesity activity of CMP. These findings suggested that a novel CMP with an increased amount of caffeine loaded onto DMN has therapeutic activity against obesity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The last few decades have seen the rise of alternative medical approaches including the use of herbal supplements, natural products, and traditional medicines, which are collectively known as 'Complementary medicines'. However, there are increasing concerns on the safety and health benefits of these medicines. One of the main hazards with the use of complementary medicines is the presence of heavy metal(loid)s such as arsenic (As), cadmium (Cd), lead (Pb), and mercury (Hg). This review deals with the characteristics of complementary medicines in terms of heavy metal(loid)s sources, distribution, bioavailability, toxicity, and human risk assessment. The heavy metal(loid)s in these medicines are derived from uptake by medicinal plants, cross-contamination during processing, and therapeutic input of metal(loid)s. This paper discusses the distribution of heavy metal(loid)s in these medicines, in terms of their nature, concentration, and speciation. The importance of determining bioavailability towards human health risk assessment was emphasized by the need to estimate daily intake of heavy metal(loid)s in complementary medicines. The review ends with selected case studies of heavy metal(loid) toxicity from complementary medicines with specific reference to As, Cd, Pb, and Hg. The future research opportunities mentioned in the conclusion of review will help researchers to explore new avenues, methodologies, and approaches to the issue of heavy metal(loid)s in complementary medicines, thereby generating new regulations and proposing fresh approach towards safe use of these medicines., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective To analyze the safety and consistency of domestic live attenuated varicella vaccines (LAVVs) at gene level.Methods The key genes (ORF38,ORF54,and ORF62) of LAVVs produced by four Chinese manufacturers were amplified by polymerase chain reaction (PCR) and sequenced.The sequencing results were compared with the sequences of Dumas,P-Oka,and V-Oka strains in GenBank and with the sequences of Varilrix (GSK) and Varivax (Merck).Results The ORF38 and ORF54 gene sequences of four domestic LAVVs were the same as each other and completely consistent with the sequences of V-Oka and Varilrix;however,it was different from Varivax (Merck) at one site.The ORF62 gene sequences of four domestic LAVVs were similar,and had individual nucleotide differences with V-Oka,Varilrix(GSK),and Varivax (Merck).Conclusions The sequences of ORF38,ORF54,and ORF62 of four domestic LAVVs are almost the same,showing good stability.They have small differences with V-Oka,Varilrix(GSK),and Varivax (Merck),without introducing new mutations.

The flavonoid baicalin has been reported to possess potent anti-inflammatory activities by suppressing inflammatory signaling pathways. However, whether baicalin can suppress the activation of NOD-like receptor (NLR) family, pyrin containing domain 3 (NLRP3) inflammasome in macrophages is largely unknown. Here, we showed that baicalin treatment dose-dependently inhibited adenosine triphosphate (ATP) or nigericin-induced NLRP3 inflammasome activation, as revealed by the decreased release of mature interleukin (IL)-1β, active caspase-1p10, and high-mobility group box-1 protein from lipopolysaccharide (LPS)-primed bone marrow-derived macrophages. The formation of ASC specks, a critical marker of NLRP3 inflammasome assembly, was robustly inhibited by baicalin in the macrophages upon ATP or nigericin stimulation. All these inhibitory effects of baicalin could be partly reversed by MDL12330A or H89, both of which are inhibitors of the protein kinase A (PKA) signaling pathway. Consistent with this, baicalin strongly enhanced PKA-mediated phosphorylation of NLRP3, which has been suggested to prevent ASC recruitment into the inflammasome. Of note, the PKA inhibitor H89 could block baicalin-induced NLRP3 phosphorylation on PKA-specific sites, further supporting PKA's role in this process. In addition, we showed that when administered pre and post exposure to Escherichia coli infection baicalin treatment significantly improved mouse survival in bacterial sepsis. Baicalin administration also significantly reduced IL-1β levels in the sera of bacterial infected mice. Altogether, our results revealed that baicalin inhibited NLRP3 inflammasome activation at least partly through augmenting PKA signaling, highlighting its therapeutic potential for the treatment of NLRP3-related inflammatory diseases.

Background and Aim: Multiple colorectal polyps are relevant in hereditary colorectal cancer (CRC) syndromes, which are thought to be caused by multiple events including germline mutations. This study was aimed to characterize germline mutations in Chinese patients with multiple colorectal polyps., Methods: Patients with > 10 colorectal polyps at the Department of Gastroenterology of the PLA Army General Hospital were enrolled from January 2014 to December 2015. These patients were divided into the high-risk, moderate-risk, and mild-risk groups. White blood cell samples were collected, and DNA was extracted to sequence a panel of 19 genes previously associated with CRC by next-generation sequencing., Results: A total of 96 patients were enrolled in the study. Pathogenic germline mutations were found in 24 (24/33, 72.73%), nine (9/24, 37.5%), and three patients (3/39, 7.7%) in the high-risk, moderate-risk, and mild-risk groups, respectively. Based on the results given, we suggested a strategy about gene sequencing test for the patients with multiple polyps, and the sensitivity and specificity of the screening strategy were 97% and 57%, respectively. Four of eight patients with MUTYH pathogenic germline mutations had the c.A934-2G monoallelic germline mutation, whereas three of eight patients had the C55T MUTYH germline mutation. Concurrent pathogenic germline mutations in APC and MUTYH were also observed., Conclusions: A genetic screening strategy comprising 19 genes was effective to screen for hereditary CRC syndromes in patients with multiple colorectal polyps. The MUTYH germline mutation hotspots in Chinese patients may be different from those in Caucasian patients., (© 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Increasing evidence supports that microRNA (miRNA)-mediated gene regulation plays a significant functional role in cancer progression. To investigate the expression and clinical significance of ITGB1 in non small cell lung cancer (NSCLC), the expression levels of ITGB1 in NSCLC tissues and human normal lung tissues were analyzed in silico using genes microarray, KEGG pathway and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Our results showed that ITGB1 was upregulated in NSCLC tissues when compared with normal lung tissues. Survival analysis based on the qRT-PCR data established that ITGB1 expression was attentively related to the prognosis of NSCLC, and patients with higher ITGB1 expression had shorter overall survival (OS). Moreover, ITGB1 was confirmed to be a direct target of miR-493-5p. Furthermore, concomitant high expression of ITGB1 and low expression of miR-493-5p correlated with a shorter median OS and PFS in NSCLC patients. In conclusion, our results provide the first evidence that ITGB1 is a direct target of miR-493-5p suggesting that ITGB1 and miR-493-5p may have potential prognostic value and may be useful as tumor biomarkers for the diagnosis of NSCLC patients.

Advanced glycation end-products (AGEs), measured by skin autofluorescence (AF), are a factor in the development or worsening of many degenerative diseases, such as diabetes and atherosclerosis. Irisin levels have been associated with diabetes, endothelial dysfunction and atherosclerosis. The objective of the present study was to investigate whether circulating irisin levels are correlated with skin AF values in type 2 diabetes patients. A total of 362 Chinese type 2 diabetic patients and 100 age- and sex-matched healthy controls were recruited in the present study. Clinical characteristics, blood biochemistry and circulating irisin levels were measured. Skin AF was measured using an AGE reader. Circulating irisin levels were significantly lower, while skin AF values were increased in type 2 diabetes compared with controls ( P <0.05 respectively). By dividing the distribution of skin AF values into tertiles, serum irisin levels gradually lowered with increasing skin AF values ( P <0.05). After adjusting for covariates, multivariate stepwise regression analysis demonstrated that serum lower irisin levels were independently associated with skin AF ( P =0.009). Circulating irisin levels were lower in type 2 diabetes patients compared with healthy controls. Lower levels of irisin are independently associated with elevated skin AF values, indicating that circulating irisin levels could be associated with AGEs accumulation, which is one of the reasons causing vascular complications in diabetic patients., (© 2017 The Author(s).)

Abstarct: The stability and reactivity of clusters are closely related to their valence electronic configuration. Doping is a most efficient method to modify the electronic configuration and properties of a cluster. Considering that Cu and S posses one and six valence electrons, respectively, the S doped Cu clusters with even number of valence electrons are expected to be more stable than those with odd number of electrons. By using the swarm intelligence based CALYPSO method on crystal structural prediction, we have explored the structures of neutral and charged Cu n+1 and Cu n S (n = 1-12) clusters. The electronic properties of the lowest energy structures have been investigated systemically by first-principles calculations with density functional theory. The results showed that the clusters with a valence count of 2, 8 and 12 appear to be magic numbers with enhanced stability. In addition, several geometry-related-properties have been discussed and compared with those results available in the literature.

Objective: Obesity is one of the risk factors for gout. The aim of the present study was to evaluate clinical characteristics of gout patients with different BMI. Methods: A total of 5 104 patients with gout were enrolled and divided into three groups according to the BMI. The clinical information was collected and relevant biochemical indices were detected. SPSS software was applied for the statistical analyses. Results: There were significant differences in the ratios of gender, regular exercise, hypertension, tophus, renal insufficiency, hyperlipidemia, impaired glucose metabolism, liver dysfunction among the three groups (all P <0.01). The onset age in overweight [45(36, 55) years] and obese subjects [40(31, 50) years] were earlier than that of the normal weight subjects [50(38, 61) years]. Moreover, waist circumstances [103(99, 108) cm and 94 (90, 98) cm vs 87 (82, 91) cm], systolic pressure [130 (120, 145) mmHg (1 mmHg=0.133 kPa)and 130(120, 140)mmHg vs 128(115, 140) mmHg], diastolic pressure [90 (80, 100) mmHg and 85 (80, 92) mmHg vs 80 (79, 90) mmHg], fasting blood glucose [5.77 (5.30, 6.44) mmol/L and 5.65 (5.19, 6.26) mmol/L vs 5.55 (5.10, 6.15) mmol/L], TG [2.10 (1.46, 3.04) mmol/L and 1.88 (1.35, 2.78) mmol/L vs 1.52 (1.07, 2.39) mmol/L], TC [5.20 (4.55, 5.93) mmol/L and 5.07 (4.46, 5.75) mmol/L vs 4.95 (4.27, 5.65) mmol/L], serum uric acid [483(418, 552) μmol/L and 461(395, 524) μmol/L vs 440 (368, 517) μmol/L], ALT [30 (21, 46) U/L and 25 (18, 36) U/L vs 21 (14, 29) U/L], AST [21(17, 28) U/L and 20 (17, 26) U/L vs 20 (6, 25) U/L], the number of joints involved [2(1, 3)joints and 2(1, 2) joints vs 1(1, 2) joints] in the overweight and obese groups were higher than those in the normal weight group ( all P <0.01). There were no statistical differences in family history, involvement of upper limb joints, kidney stones and coronary heart disease among the three groups (all P >0.05). Conclusions: Obesity is associated with an earlier age of gout onset.With the increase of BMI, the blood pressures, glucose, lipid, serum uric acid, liver transaminase levels and the number of involved joints increased gradually. Cautions should be taken in treating patients with different BMI.

Dicer1 is an enzyme essential for microRNA (miRNA) maturation. The loss of miRNAs resulted from Dicer1 deficiency greatly contributes to the progression of many diseases, including lipid dysregulation, but its role in hepatic accumulation of free cholesterol (FC) that is critical in the development of non-alcoholic steatohepatitis (NASH) remains elusive. In this study, we used the liver-specific Dicer1-knockout mice to identify the miRNAs involved in hepatic FC accumulation. In a widely used dietary NASH model, mice were fed a methionine-choline-deficient (MCD) diet for 3 weeks, which resulted in significant increase in hepatic FC levels as well as decrease of Dicer1 mRNA levels in livers. The liver-specific Dicer1-knockout induced hepatic FC accumulation at 5-6 weeks, accompanied by increased mRNA and protein levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a rate-limiting enzyme of cholesterol synthesis in livers. Eleven predicted miRNAs were screened, revealing that miR-29a/b/c significantly suppressed HMGCR expression by targeting the HMGCR mRNA 3'-UTR. Overexpression of miR-29a in SMMC-7721 cells, a steatosis hepatic cell model, significantly decreased HMGCR expression and the FC level. Furthermore, the expression levels of miR-29a were inversely correlated with HMGCR expression levels in the MCD diet mouse model in vivo and in 2 steatosis hepatic cell models (SMMC-7721 and HL-7702 cells) in vitro. Our results show that Dicer1/miR-29/HMGCR axis contributes to hepatic free cholesterol accumulation in mouse NASH, and miR-29 may serve as an important regulator of hepatic cholesterol homeostasis. Thus, miR-29a could be utilized as a potential therapeutic target for the treatment of non-alcoholic fatty liver disease as well as for other liver diseases associated with FC accumulation.

Objective: To investigate the feasibility and security of robotic resection of tumor in segment Ⅷ primarily. Methods: The clinicopathologic data of 7 patients who underwent robotic resection of tumor in segment Ⅷ using daVinci robotic system in the Department of Hepato-pancreato-biliary Surgical Oncology, Chinese PLA General Hospital from June 2016 to December 2016 were retrospectively analyzed. The lesion size, the tumor malignance degree mean operation time, intraoperative blood loss and the rate of conversion to laparotomy, postoperative hospital stay, mobidity and motality of all the 7 patients were collected. Results: All the 7 operations were successfully performed with radical resection.The mean tumor diameter was (4.6±1.2)cm. The mean operation time, intraoperative blood loss and postoperative hospital stay were(120.7±21.7)min, (100±106.7)ml, and(7.3±1.8)days respectively.All the patients were discharged successfully with no severe complications. Conclusions: According to our experiences, as a new operationmodel of minimally invasive surgery, robotic resection of tumor in segment Ⅷ has manyadvantages in laparoscopic like less trauma, less intraoperative bleeding, light postoperative pain, shorter postoperative hospital stay and so on. There are some certain advantages in exposure of Ⅷ segment under robotic surgery system. Robotic surgery system is safe and feasible for tumorresection of segmentⅧ, andhas clinical promoting value and application prospect.

Objective: General anesthesia impairs spatial learning and memory in neonatal rats. The aim of this study was to investigate whether the Wnt pathway was involved in neonatal isoflurane and sevoflurane exposure-induced neurocognitive impairment., Materials and Methods: Sprague-Dawley rats were randomly assigned to administration isoflurane or sevoflurane for 6 hours at postnatal 7 days. Wnt inhibitor XAV 939 was administrated 30 min before anesthesia. Morris water maze was used to test the learning and memory at 5-week and 10-week. Hematoxylin and Eosin (H&E) stain was performed to evaluation the neuronal death in the hippocampus. Quantitative Real-time PCR (q-PCR) and Western blot assays were used to measure mRNA and proteins expression levels of the Wnt3a, GSK 3β and β-catenin, respectively., Results: The results showed that isoflurane or sevoflurane could significantly increase neonatal death and cell lost in the developing brain and the Wnt inhibitor could improve the cell degeneration. It demonstrated that isoflurane or sevoflurane could impair the P7 rats learning and memory capability, while these effects were reduced over time. When rats treated Wnt inhibitor at 30 min before anesthesia, the impairment of brain could relieve. q-PCR and Western blot demonstrated that isoflurane or sevoflurane affects expression levels of Wnt3a, GSK 3β and β-catenin. These results suggested that impairment of learning and memory in P7 rats may be related to the Wnt signaling pathway., Conclusions: The results suggested general anesthesia treatment led to increased brain cell degeneration and impaired learning and memory in P7 rats via Wnt signaling pathway.

Rationale: Idiopathic or heritable pulmonary arterial hypertension is characterized by loss and obliteration of lung vasculature. Endothelial cell dysfunction is pivotal to the pathophysiology, but different causal mechanisms may reflect a need for patient-tailored therapies., Objectives: Endothelial cells differentiated from induced pluripotent stem cells were compared with pulmonary arterial endothelial cells from the same patients with idiopathic or heritable pulmonary arterial hypertension, to determine whether they shared functional abnormalities and altered gene expression patterns that differed from those in unused donor cells. We then investigated whether endothelial cells differentiated from pluripotent cells could serve as surrogates to test emerging therapies., Methods: Functional changes assessed included adhesion, migration, tube formation, and propensity to apoptosis. Expression of bone morphogenetic protein receptor type 2 (BMPR2) and its target, collagen IV, signaling of the phosphorylated form of the mothers against decapentaplegic proteins (pSMAD1/5), and transcriptomic profiles were also analyzed., Measurements and Main Results: Native pulmonary arterial and induced pluripotent stem cell-derived endothelial cells from patients with idiopathic and heritable pulmonary arterial hypertension compared with control subjects showed a similar reduction in adhesion, migration, survival, and tube formation, and decreased BMPR2 and downstream signaling and collagen IV expression. Transcriptomic profiling revealed high kisspeptin 1 (KISS1) related to reduced migration and low carboxylesterase 1 (CES1), to impaired survival in patient cells. A beneficial angiogenic response to potential therapies, FK506 and Elafin, was related to reduced slit guidance ligand 3 (SLIT3), an antimigratory factor., Conclusions: Despite the site of disease in the lung, our study indicates that induced pluripotent stem cell-derived endothelial cells are useful surrogates to uncover novel features related to disease mechanisms and to better match patients to therapies.

Objectives: To observe the regulation of Chinese herbal medicine, Modifified Qing'e Pill (, MQEP), on the expression of adiponectin, bone morphogenetic protein 2 (BMP2), osteoprotegerin (OPG) and other potentially relevant risk factors in patients with nontraumatic osteonecrosis of the femoral head (ONFH)., Methods: A total of 96 patients with nontraumatic ONFH were unequal randomly divided into treatment group (60 cases) and control group (36 cases). The treatment group were treated with MQEP while the control group were treated with simulated pills. Both groups were given caltrate D. Six months were taken as a treatment course. Patients were followed up every 2 months. The levels of plasma adiponectin, BMP2, OPG, von Willebrand factor (vWF), von Willebrand factor cleaving protease (vWF-cp), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), C-reactive protein (CRP), blood rheology, bone mineral density (BMD) of the femoral head and Harris Hip Score were measured before and after treatment., Results: After 6 months of treatment, compared with the control group, patients in the treatment group had signifificantly higher adiponectin and BMP2 levels (P<0.01 and P=0.013, respectively), lower vWF, PAI-1 and CRP levels (P=0.019, P<0.01 and P<0.01, respectively), and lower blood rheology parameters. BMD of the femoral neck, triangle area and Harris Hip Score in the treatment group were signifificantly higher than those in the control group. Moreover, plasma adiponectin showed a positive association with BMP2 (r=0.231, P=0.003) and a negative association with PAI-1 (r=-0.159, P<0.05)., Conclusion: MQEP may play a protective role against nontraumatic ONFH by increasing the expression of adiponectin, regulating bone metabolism and improving the hypercoagulation state, which may provide an experimental base for its clinical effects.

Indirect immunofluorescence imaging of human epithelial type 2 (HEp-2) cell image is an effective evidence to diagnose autoimmune diseases. Recently, computer-aided diagnosis of autoimmune diseases by the HEp-2 cell classification has attracted great attention. However, the HEp-2 cell classification task is quite challenging due to large intraclass and small interclass variations. In this paper, we propose an effective approach for the automatic HEp-2 cell classification by combining multiresolution co-occurrence texture and large regional shape information. To be more specific, we propose to: 1) capture multiresolution co-occurrence texture information by a novel pairwise rotation-invariant co-occurrence of local Gabor binary pattern descriptor; 2) depict large regional shape information by using an improved Fisher vector model with RootSIFT features, which are sampled from large image patches in multiple scales; and 3) combine both features. We evaluate systematically the proposed approach on the IEEE International Conference on Pattern Recognition (ICPR) 2012, the IEEE International Conference on Image Processing (ICIP) 2013, and the ICPR 2014 contest datasets. The proposed method based on the combination of the introduced two features outperforms the winners of the ICPR 2012 contest using the same experimental protocol. Our method also greatly improves the winner of the ICIP 2013 contest under four different experimental setups. Using the leave-one-specimen-out evaluation strategy, our method achieves comparable performance with the winner of the ICPR 2014 contest that combined four features.

Aim: To explore the induction effects and mechanism of Solanum lyratum Thumb (ST) on human hepatocellular carcinoma SMMC-7721 cells through the mitochondrial pathway., Methods: The experiments were conducted on three groups: an experimental group (with ST ethanol extracts' concentration being 2.5, 5 and 10 mg/L), a negative control group (with only nutrient solution, 0 mg/L ST ethanol extracts), and a positive control group (2.5 mg/L DDP). The inhibition rate of cell proliferation was checked by using the methyl thiazolyl tetrazolium method, and cell apoptosis was tested by TUNEL method. Furthermore, RT-PCR was used to examine mRNA expression of Fas, FasL, caspase-8, caspase-3, p53 and Bcl-2 genes., Results: Compared with the negative control group, the inhibition and apoptosis rates of the experimental group with different concentrations of ST extracts on human hepatocellular carcinoma SMMC-7721 cells significantly increased ( P < 0.05). Besides, the mRNA expression of FasL and Bcl-2 significantly decreased ( P < 0.05) while the mRNA expression of Fas, caspase-8, caspase-3 and p53 increased significantly. When compared with the positive control group, the experimental groups with 5 mg/L ST ethanol extracts showed effects similar to the positive control group., Conclusion: ST ethanol extracts induced the apoptosis of hepatocellular carcinoma SMMC-7721 cells through up-regulated Fas, caspase-8, caspse-3 and p53, and down-regulated FasL and Bcl-2 in the mitochondrial pathway., Competing Interests: Conflict-of-interest statement: We declare that there are no conflicts of interest to disclose.

A photocatalytic cascade cyclization of 1,7-enynes with acyl chlorides has been established. This method offers an operationally simple access to diverse fused pyran derivatives with a broad substrate scope in high yields from simple acyl chlorides via an acyl radical intermediate.

Objective * These authors contributed equally to this work. To explore tendon-bundle technique for treating Achilles tendon rupture with no defects. Methods Patients with full unilateral Achilles tendon rupture with no defects were included. The Achilles tendon medial edge surgical repair approach was used, revealing horsetail-like rupture bundles. Tendon bundles were anatomically realigned and repaired end-to-end using 5-0 sutures. Patients were followed-up for 1 year, and assessed for differences between the repaired versus healthy limb. Results Out of 24 patients (18 male, 6 female; aged 19-56 years) at 1 year following surgery, mean American Orthopaedic Foot and Ankle Society score was 92.4 ± 5.9; mean differences between the surgically repaired versus contralateral side in dorsiflexion and plantarflexion angle were 3.5 ± 2.3° and 5.6 ± 3.2°, respectively; mean difference in calf circumference between the two sides was 0.9 ± 0.5 cm; and mean increase in Achilles tendon width versus the healthy side was 0.8 ± 0.2 cm. By 1 year post-surgery, there were no significant between-side differences in dorsiflexion and plantarflexion angle, or calf circumference. Conclusions Tendon-bundle surgery resulted in good ankle function restoration and low complication rates. Tendon-bundle surgery may reduce blood supply destruction and maximally preserve Achilles tendon length, and may be effective for treating Achilles tendon rupture with no defects.

In order to analyze the effects of combined application of water retention agent and orga-nic fertilizer on physico-chemical properties of iron tailings and to find the optimal proportion of water retention agent and organic fertilizer for the improvement of iron tailings, the experimental plots of the combination trials with 2 factors in 4 levels were designed in the iron tailings of Qian'an Shougang through investigating some indexes of physico-chemical properties such as bulk density, moisture capacity, porosity, pH and the contents of organic matter, nitrogen, phosphorus and potas-sium. The biomasses of Medicago sativa and Amorpha fruticosa planted in the experimental plots were measured to verify the improvement effects. 4 levels of super absorbent polymers (L·m -3 ) used in treatments were 0 (B 0 ), 10 (B 1 ), 50 (B 2 ), 100 (B 3 ), and 4 levels of organic fertilizer (kg·m -2 ) were 0(N 0 ), 2.25 (N 1 ), 11.24 (N 2 ), 22.49 (N 3 ). The improving effects of different treatments on physico-chemical properties of iron tailings were mainly reflected in the surface layer of 0-20 cm. All the tested indexes were significantly different from control (CK) in the layer of 0-20 cm. The improvement effects of organic fertilizer on physical and chemical properties of iron tai-lings were better than that of water retention agent. In the 0-20 cm layer, the bulk density, non-capillary porosity, organic matter, rapidly available phosphorus, and available potassium under all treatments of adding water retention agent individually were not significantly different from the CK, while significant difference was observed when the organic fertilizer was solely applied in B 0 N 2 and B 0 N 3 treatments. The improvement synergy effect of organic fertilizer and water retention agent was better than that of organic fertilizer or water retention agent, respectively. In 0-20 cm layer, all the indexes obtained from treatment B 3 N 3 performed best and were significantly different from the CK, which was the optimum for the improvement of iron tailings.

Amphetamine (AMPH) or methamphetamine (METH) abuse can cause oxidative damage and is a risk factor for diseases including pulmonary arterial hypertension (PAH). Pulmonary artery endothelial cells (PAECs) from AMPH-associated-PAH patients show DNA damage as judged by γH2AX foci and DNA comet tails. We therefore hypothesized that AMPH induces DNA damage and vascular pathology by interfering with normal adaptation to an environmental perturbation causing oxidative stress. Consistent with this, we found that AMPH alone does not cause DNA damage in normoxic PAECs, but greatly amplifies DNA damage in hypoxic PAECs. The mechanism involves AMPH activation of protein phosphatase 2A, which potentiates inhibition of Akt. This increases sirtuin 1, causing deacetylation and degradation of HIF1α, thereby impairing its transcriptional activity, resulting in a reduction in pyruvate dehydrogenase kinase 1 and impaired cytochrome c oxidase 4 isoform switch. Mitochondrial oxidative phosphorylation is inappropriately enhanced and, as a result of impaired electron transport and mitochondrial ROS increase, caspase-3 is activated and DNA damage is induced. In mice given binge doses of METH followed by hypoxia, HIF1α is suppressed and pulmonary artery DNA damage foci are associated with worse pulmonary vascular remodeling. Thus, chronic AMPH/METH can induce DNA damage associated with vascular disease by subverting the adaptive responses to oxidative stress., Competing Interests: The authors have declared that no conflict of interest exists.

EGFR and VEGFR-2 are involved in pathological disorders and the progression of different kinds of tumors, the combined blockade of EGFR and VEGFR signaling pathways appears to be an attractive approach to cancer therapy. In this work, a series of 4-anilinoquinazoline derivatives containing substituted diaryl urea or glycine methyl ester moiety were designed and identified as EGFR and VEGFR-2 dual inhibitors. Compounds 19i, 19j and 19l exhibited the most potent inhibitory activities against EGFR (IC 50  = 1 nM, 78 nM and 51 nM, respectively) and VEGFR-2 (IC 50  = 79 nM, 14 nM and 14 nM, respectively), they showed good antiproliferative activities as well. Molecular docking established the interaction of 19i with the DFG-out conformation of VEGFR-2, suggesting that they might be type II kinase inhibitors., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The isoquinoline alkaloid berberine possesses many pharmacological activities including antibacterial infection. Although the direct bactericidal effect of berberine has been documented, its influence on the antibacterial functions of macrophages is largely unknown. As inflammasome activation in macrophages is important for the defense against bacterial infection, we aimed to investigate the influence of berberine on inflammasome activation in murine macrophages. Our results showed that berberine significantly increased ATP-induced inflammasome activation as reflected by enhanced pyroptosis as well as increased release of caspase-1p10 and mature interleukin-1β (IL-1β) in macrophages. Such effects of berberine could be suppressed by AMP-activated protein kinase (AMPK) inhibitor compound C or by knockdown of AMPKα expression, indicating the involvement of AMPK signaling in this process. In line with increased IL-1β release, the ability of macrophages to kill engulfed bacteria was also intensified by berberine. This was corroborated by the in vivo finding that the peritoneal live bacterial load was decreased by berberine treatment. Moreover, berberine administration significantly improved survival of bacterial infected mice, concomitant with increased IL-1β levels and elevated neutrophil recruitment in the peritoneal cavity. Collectively, these data suggested that berberine could enhance bacterial killing by augmenting inflammasome activation in macrophages through AMPK signaling.

Previous studies have shown that microRNA-1304 (miR-1304) is dysregulated in certain types of cancers, including non-small cell lung cancer (NSCLC), and might be involved in tumor survival and/or growth. In this study we investigated the direct target of miR-1304 and its function in NSCLC in vitro. Human lung adenocarcinoma cell lines (A549 and NCI-H1975) were studied. The cell proliferation and survival were investigated via cell counting, MTT and colony-formation assays. Cell apoptosis and cell cycle were examined using annexin V-PE/7-AAD and PI staining assays, respectively. The dual-luciferase reporter assay was used to verify post-transcriptional regulation of heme oxygenase-1 (HO-1) by miR-1304. CRISPR/Cas9 was used to deplete endogenous miR-1304. Overexpression of MiR-1304 significantly decreased the number and viability of NSCLC cells and colony formation, and induced cell apoptosis and G 0 /G 1 phase cell cycle arrest. HO-1 was demonstrated to be a direct target of miR-1304 in NSCLC cells. Restoration of HO-1 expression by hemin (20 μmol/L) abolished the inhibition of miR-1304 on cell growth and rescued miR-1304-induced apoptosis in A549 cells. Suppression of endogenous miR-1304 with anti-1304 significantly increased HO-1 expression and promoted cell growth and survival in A549 cells. In 17 human NSCLC tissue samples, miR-1304 expression was significantly decreased, while HO-1 expression was significantly increased as compared to normal lung tissues. MicroRNA-1304 is a tumor suppressor and HO-1 is its direct target in NSCLC. The results suggest the potential for miR-1304 as a therapeutic target for NSCLC.

There is a recognized challenge in analyzing traditional Chinese medicine formulas because of their complex chemical compositions. The application of modern analytical techniques such as high-performance liquid chromatography coupled with a tandem mass spectrometry has improved the characterization of various compounds from traditional Chinese medicine formulas significantly. This study aims to conduct a bibliometric analysis to recognize the overall trend of high-performance liquid chromatography coupled with tandem mass spectrometry approaches in the analysis of traditional Chinese medicine formulas, its significance and possible underlying interactions between individual herbs in these formulas. Electronic databases were searched systematically, and the identified studies were collected and analyzed using Microsoft Access 2010, Graph Pad 5.0 software and Ucinet software package. 338 publications between 1997 and 2015 were identified, and analyzed in terms of annual growth and accumulated publications, top journals, forms of traditional Chinese medicine preparations and highly studied formulas and single herbs, as well as social network analysis of single herbs. There is a significant increase trend in using high-performance liquid chromatography coupled with tandem mass spectrometry related techniques in analysis of commonly used forms of traditional Chinese medicine formulas in the last 3 years. Stringent quality control is of great significance for the modernization and globalization of traditional Chinese medicine, and this bibliometric analysis provided the first and comprehensive summary within this field., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Adenosine triphosphate (ATP) is released by bacteria and host cells during bacterial infection as well as sterile tissue injury, acting as an inducer of inflammasome activation. Previous studies have shown that ATP treatment leads to AMP-activated protein kinase (AMPK) activation. However, it is unclear whether AMPK signaling has been involved in the regulation of ATP-induced inflammasome activation and subsequent pyroptosis. In this study, we aimed to investigate this issue in lipopolysaccharide-activated murine macrophages. Our results showed that AMPK signaling was activated in murine macrophages upon ATP treatment, which was accompanied by inflammasome activation and pyroptosis as evidenced by rapid cell membrane rupture as well as mature interleukin (IL)-1β and active caspase-1p10 release. The ATP-induced inflammasome activation and pyroptosis were markedly suppressed by an AMPK inhibitor compound C or small-interfering RNA-mediated knockdown of AMPK α, but could be greatly enhanced by metformin (a well-known AMPK agonist). Importantly, metformin administration increased the mortality of mice with bacterial sepsis, which was likely because metformin treatment enhanced the systemic inflammasome activation as indicated by elevated serum and hepatic IL-1β levels. Collectively, these data indicated that the AMPK signaling positively regulated ATP-induced inflammasome activation and pyroptosis in macrophages, highlighting the possibility of AMPK-targeting therapies for inflammatory diseases involving inflammasome activation.

Squamous cell carcinoma of the lung is one of the most aggressive cancers, and its aggressiveness is in part due to its intrinsic high rate of metastasis. Moreover, the process of epithelial-mesenchymal transition (EMT) appears to be involved in these neoplastic processes. Furthermore, EMT-type cells share many biological characteristics with the function of angiogenin (ANG) in squamous cell lung carcinoma. We conducted immunohistochemical analysis to detect the expression of ANG, E-cadherin, vimentin, N-cadherin, β-catenin and TGF-β1 in 60 cases of squamous cell lung carcinoma tissues. Western blot analysis was adopted to detect the protein expression levels of ANG and EMT markers. The effects of ANG on proliferation, migration and invasion of squamous cell lung carcinoma cells was analyzed by Cell Counting Kit-8, scratch assay and Transwell invasion chamber in order to reveal the role of ANG in the process of EMT in squamous cell lung carcinoma. The results revealed that ANG was aberrantly expressed in the squamous cell lung carcinoma specimens and was closely correlated with the differentiation of the cell lines. The expression of ANG was also significantly associated with metastasis and the stage of the squamous cell lung carcinoma cases. In addition, we validated that ANG influenced the expression of vimentin, E-cadherin, N-cadherin, β-catenin and TGF-β1 in SK-MES-1 cells. Most importantly, overexpression of ANG enhanced the migration and invasion of SK-MES-1 cells, while knockdown resulted in opposite effects. In the present study, we found that ANG plays an important role in EMT in squamous cell lung carcinoma and may be a valuable therapeutic target for squamous cell lung carcinoma.

Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Piperine is a phytochemical present in black pepper ( Piper nigrum Linn) and other related herbs, possessing a wide array of pharmacological activities including anti-inflammatory effects. Previously, we demonstrated that piperine has therapeutic effects on bacterial sepsis in mice, but the underlying mechanism has not been fully elucidated. In this study, we aimed to investigate the influences of piperine on pyroptosis in murine macrophages. The results showed that piperine dose-dependently inhibited ATP-induced pyroptosis, thereby suppressing interleukin-1β (IL-1β) or high mobility group box-1 protein (HMGB1) release in LPS-primed bone marrow-derived macrophages and J774A.1 cells. Accompanying this, ATP-induced AMP-activated protein kinase (AMPK) activation was greatly suppressed by piperine, whereas AMPK agonist metformin counteracted piperine's inhibitory effects on pyroptosis. Moreover, piperine administration greatly reduced both peritoneal and serum IL-1β levels in the mouse model intraperitoneally infected with Escherichia coli , suggestive of suppressing systemic inflammation and pyroptosis. Our data indicated that piperine could protect macrophages from pyroptosis and reduced IL-1β and HMGB1 release by suppressing ATP-induced AMPK activation, suggesting that piperine may become a potential therapeutic agent against bacterial sepsis.

Background: Two vaccination schedules where inactivated polio vaccine (IPV) was followed by oral polio vaccine (OPV) were compared to an OPV-only schedule., Methods: Healthy Chinese infants received a 3-dose primary series of IPV-OPV-OPV (Group A), IPV-IPV-OPV (Group B), or OPV-OPV-OPV (Group C) at 2, 3, and 4 months of age. At pre-Dose 1, 1-month, and 14-months post-Dose 3, polio 1, 2, and 3 antibody titers were assessed by virus-neutralizing antibody assay with Sabin or wild-type strains. Adverse events were monitored., Results: Anti-polio 1, 2, and 3 titers were ≥8 (1/dil) in >99% of participants, and Group A and Group B were noninferior to Group C at 1-month post-Dose 3 as assessed by Sabin strain-based assay (SSBA). In Group A 1-month post-Dose 3, there was no geometric mean antibody titers (GMT) differences for types 1 and 3; type 2 GMTs were ≈3-fold higher by wild-type strain-based assay (WTBA) versus SSBA. For Group B, GMTs were ≈1.7- and 3.6-fold higher for types 1 and 2 via WTBA, while type 3 GMTs were similar. For Group C, GMTs were ≈6.3- and 2-fold higher for types 1 and 3 with SSBA, and type 2 GMTs were similar. Antibodies persisted in >96.6% of participants. Adverse event incidence in each group was similar., Conclusions: A primary series of 1 or 2 IPV doses followed by 2 or 1 OPV doses was immunogenic and noninferior to an OPV-only arm. SSBA was better at detecting antibodies elicited by OPV with antibody titers correlated to the number of OPV doses (NCT01475539)., (© The Author 2015. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Retinal detachment is a serious vision threatening disease. Current consensus for the treatment of retinal detachment is to reattach the retina onto the choroid layer by drainage of accumulated subretinal fluid. Although several surgical methods have been developed, no satisfactory visual outcome has been obtained without surgical complications such as unintended puncture and hemorrhage of the retina and choroid tissue. In this study, we developed a novel Curved-Micro-Drainer (CMD) for the innocuous drainage of subretinal fluid. It is a curved structure with a 15° beveled tip that is 5 mm in length, with an 80 μm inner diameter and a 100 μm outer diameter. This high inner-to-outer diameter ratio of CMD with a 100 μm outer diameter allows efficient drainage of highly viscous subretinal fluid in a minimally invasive manner. In addition, the curved structure precisely matches the spherical ocular structure, which facilitates the CMD insertion into the subretinal space without choroid tissue damage. We demonstrate that the optimized CMD allows for the innocuous drainage of the viscous subretinal fluid from the porcine eye, whereas the traditional hypodermic needle (31-gauge) induces severe retinal and choroid damage. CMD can overcome a critical safety issue and is a potential alternative to conventional surgical interventions for the innocuous drainage of subretinal fluid.

Three new sulphur glycosides, raphanuside B-D (1-3), together with a known sulphur glycoside, raphanuside (4) were isolated from the decoction of the seeds of Descurainia sophia (L.) Webb ex Prantl, and the compound 4 was reported for the first time from this plant. Their structures were identified by means of UV, IR, 1D, 2D NMR (HSQC, HMBC and NOESY) and HR-ESI-MS spectroscopic data.

Objective: To assess a classification system for midfoot injury that was based on the characteristics of the foot malunion and to evaluate the suggested treatment strategies., Methods: This retrospective review of data from patients with posttraumatic midfoot malunion categorized each foot deformity into one of three types based on the foot arch and then separated these categories into one of three subtypes based on the forefoot deformity. According to the types of malunion, fascio-cutaneous flap, osteotomy, joint arthrodesis or realignment was used to correct the deformity. Patients were assessed before surgery and at 12 and 24 months postoperation., Results: Of the 24 patients identified, six had Lisfranc joint injuries, nine had Lisfranc joint complex injuries combined with cuboid compression fractures and nine had Lisfranc joint complex injuries combined with navicular fractures. Overall, eight patients presented with poor soft tissue and massive scar at the dorsal foot. Visual analogue scale and American Orthopaedic Foot and Ankle Society midfoot scores significantly improved over the 24-month study period. At the end of the study, 21 of 24 patients (87.5%) rated their functional outcome as excellent or good., Conclusion: The classification of the midfoot malunion evaluated in this study may be helpful in the decision making process for surgical intervention., (© The Author(s) 2016.)

Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

According to the fundamental absorption properties of Carbon Monoxide(CO) near 4.7 μm, a novel CO sensor was designed using a Quantum Cascaded Laser (QCL) whose central wavelength is 4.75 μm and Multi-pass Gas Cell (MGC). This sensor uses a QCL with the thermoelectrically cooled function and can work under pulse mode and room temperature, the exiting optical wavelength was located in a strong absorption line (2 103 cm-1)which is in the base band of CO through adjusting the injection current and temperature. Meanwhile, a novel MGC (40 cm long and 800 mL sampling volume) with 16 meters effective optical path length and mercury cadmium telluride mid-infrared detectors was used, thus effectively improved the sensitivity of this system. Additionally, a reference gas cell and a spatial filtering optical structure were occupied, resulting in effective improvement of the beam quality and reduction of the noise caused by the instability of QCL, the sensitivity of this system was improved furtherly. It indicated that the system works stably by means of multiple measurements to the carbon monoxide gas with different concentration, a detection limit of 5 μmol·mol-1 can be obtained when the signal-to-noise ratio equals 1.

According to the principle of mid-infrared absorption spectrum, the fundamental absorption characteristics at the wavelength of 7.5 μm of methane (CH4) molecule was used to design a mid-infrared quantum cascaded laser (QCL) and multi-pass gas cell (MPC)-based methane gas sensor. This sensor uses a thermoelectrically cooled, pulse mode QCL whose central wavelength is 7.5 μm. The QCL wavelength was scanned over CH4 absorption line (1 332.8 cm-1)through adjusting the injection current under the condition of room temperature. Meanwhile, a compact MPC (40 cm long and 800 mL sampling volume) was utilized to achieve an effective optical path length of 16 meters. Additionally, a reference gas cell was occupied and joined a spatial filtering optical structure to meet the requirement of MPC in incidence beam, effectively improved the beam quality, reduced the noise which is caused by the fluctuation of QCL and improved the detection sensitivity of this instrument under the guidance of differential optical absorption spectroscopy method. It indicated that the stability of this instrument is good by means of multiple measurements to the methane gas with different concentration, a detection limit of 1 μmol·mol-1 will be obtained when the signal-to-noise ratio equals 1.

Objective: To determine the mechanism of Angiogenin(ANG) function involved in the carcinogenesis of lung squamous cell carcinoma., Methods: 12 patients' normal tissue and cancerous tissue were collected. ANG expression in the squamous cell carcinoma of the lung was evaluated by qRT-PCR and western-blot. The regulation of ANG on proliferation, migration, invasion, and apoptosis of SK-MES-1 cells were analyzed by Cell Counting Kit-8, Transwell migration chamber, Transwell invasion chamber, and Annexin V-FITC assay, respectively. PCR array was utilized for screening potential target genes of ANG. Chromatin immunoprecipitation(ChIP) assays and luciferase assay were adopted for investigation of ANG's direct regulation on HMGA2., Results: ANG expression is increased in the squamous cell carcinoma of the lung tissue. In vitro experiments results indicated that overexpression of ANG promotes proliferation and invasion capability of SK-MES-1 cells. The candidate proliferation, migration, and invasion related ANG target gene found was HMGA2, expression levels of which were also enhanced in lung squamous cell carcinoma tissue. The direct regulation of ANG on HMGA2 was verified by ChIP and luciferase assay results. Furthermore, down-regulating HMGA2 significantly alleviated the suppression effects of ANG on proliferation, migration, and invasion of SK-MES-1 cells., Conclusions: Our data illustrated the mechanisms that ANG promoted the cell of SQCLC proliferation, migration, and invasion capacity via directly up-regulating HMGA2.

Objective: To investigate the etiology of unilateral sinonasal disease and clinical features. Method: The clinic data of 92 patients with unilateral sinonasal diseases were analyzed. Result: 42 cases of chronic sinusitis (31 cases of nasal polyps), 17 cases of nasal inverted papilloma, 9 cases of sinus fungal disease, 6 cases of odontogenic maxillary sinusitis, 3 cases of maxillary choanal polyp, 4 cases of nasal blood vessels tumor, 3 cases of sinus osteoma, 6 cases of sinus cyst, 2 cases of sinonasal malignancies. Conclusion: Among unilateral sinonasal diseases, chronic sinusitis, nasal polyps are very common, but there are still more than half of the other pathological changes, the most common one is the nasal inverted papilloma. Therefore, more attention should be paid to the preoperative differential diagnosis., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Unlabelled: Many epidemiological studies have shown that in some tumors carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and β-catenin appear to be related. However, it remains to be established whether CEACAM1 is related to β-catenin in osteoporosis. Here, we reveal that CEACAM1 might influence the canonical Wnt/β-catenin pathway to modulate bone metabolism in postmenopausal osteoporosis., Introduction: The aim of this study is to assess the serum level of CEACAM1 in postmenopausal women and its correlation with β-catenin and bone mineral density (BMD)., Methods: The BMD was measured at the lumbar spine (L1-L4) or the femoral neck using dual-energy X-ray absorptiometry (DXA). Serum CEACAM1, β-catenin, receptor activator of nuclear factor kappa-B (RANKL), osteoprotegerin (OPG), β-isomerized C-terminal crosslinking of type I collagen (β-CTX), intact N-terminal propeptide of type I collagen (PINP), estradiol, and insulin were measured in 350 postmenopausal women. Patients were divided according to lumbar spine or femur neck T-scores into osteoporosis (group I), osteopenia (group II), and normal bone mineral density, the latter serving as control., Results: Serum CEACAM1 levels were significantly lower in group I and II compared to those in control subjects (P < 0.001). Serum CEACAM1 levels correlated positively with β-catenin and BMD, but correlated negatively to the ratio between RANKL and OPG., Conclusion: This study provides evidence that decreased serum CEACAM1 levels are related to low BMD in postmenopausal women, and that serum CEACAM1 levels correlated positively to β-catenin. It suggests that CEACAM1 might influence the canonical Wnt/β-catenin pathway to modulate bone metabolism.

Introduction: Replacing live-attenuated oral poliovirus vaccines (OPV) with inactivated poliovirus vaccines (IPV) is part of the global strategy to eradicate poliomyelitis. China was declared polio-free in 2000 but continues to record cases of vaccine-associated-poliomyelitis and vaccine-derived-poliovirus outbreaks. Two pilot safety studies and two larger immunogenicity trials evaluated the non-inferiority of IPV (Poliorix™, GSK Vaccines, Belgium) versus OPV in infants and booster vaccination in toddlers primed with either IPV or OPV in China., Methods: In pilot safety studies, 25 infants received 3-dose IPV primary vaccination (Study A, www.clinicaltrial.gov NCT00937404) and 25 received an IPV booster after priming with three OPV doses (Study B, NCT01021293). In the randomised, controlled immunogenicity and safety trial (Study C, NCT00920439), infants received 3-dose primary vaccination with IPV (N=541) or OPV (N=535) at 2,3,4 months of age, and a booster IPV dose at 18-24 months (N=470, Study D, NCT01323647: extension of study C). Blood samples were collected before and one month post-dose-3 and booster. Reactogenicity was assessed using diary cards. Serious adverse events (SAEs) were captured throughout each study., Results: Study A and B showed that IPV priming and IPV boosting (after OPV) was safe. Study C: One month post-dose-3, all IPV and ≥ 98.3% OPV recipients had seroprotective antibody titres towards each poliovirus type. The immune response elicited by IPV was non-inferior to Chinese OPV. Seroprotective antibody titres persisted in ≥ 94.7% IPV and ≥ 96.1% OPV recipients at 18-24 months (Study D). IPV had a clinically acceptable safety profile in all studies. Grade 3 local and systemic reactions were uncommon. No SAEs were related to IPV administration., Conclusion: Trivalent IPV is non-inferior to OPV in terms of seroprotection (in the Chinese vaccination schedule) in infant and toddlers, with a clinically acceptable safety profile., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Four new species of Psechrus are described from Yunnan Province: P. changminae sp. nov., P. conicus sp. nov., P. discoideus sp. nov. and P. spatulatus sp. nov. Herewith the number of species belonging to Psechrus in Yunnan Province extended from five to nine. Illustrations and colour photos are provided, with comparison of intraspecific variation of copulatory organs.