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We conducted a crossover study employing air cleaner intervention among 125 schoolchildren aged 9-12 years in a boarding school in Beijing, China. The PM concentrations were monitored, and 27 biomarkers were analyzed. We used the linear mixed-effects model to evaluate the association of intervention/time-weighted PM concentrations with biomarkers. The outcomes showed that air cleaner intervention was associated with FeNO, exhaled breath condensate (EBC) IL-1β, and IL-6, which decreased by 12.57%, 10.83%, and 4.33%, respectively. Similar results were observed in the associations with PMs. Lag 1 day PMs had the strongest relationship with biomarkers, and significant changes were observed in biomarkers such as FEV1, FeNO, EBC 8-iso, and MCP-1. Boys showed higher percentage changes than girls, and the related biomarkers were FeNO, EBC 4-HNE, IL-1β, IL-6, and MCP-1. The results showed that biomarkers such as FeNO, EBC IL-6, MCP-1, and 4-HNE could sensitively reflect the early abnormal response of the respiratory system under short-term PM exposure among healthy schoolchildren and indicated that (1) air cleaners exert a protective effect on children's respiratory system. (2) PM had lag and cumulative effect, lag 1 day had the greatest effect. (3) The boys were more sensitive than the girls.

Herein, we reported 3 cases of angiosarcoma (AS) of the head and neck in old patients, and the etiology, pathogenesis, histopathology, immunohistochemistry, diagnosis, differential diagnosis and prognosis were discussion. Case 1, a male patient aged 86 years old was admitted due to purplish erythema on the head and face and progressive purplish edema in the orbit of the eye for 3 years. He was misdiagnosed with connective tissue disease in another hospital, and a second biopsy and histopathological examination confirmed the AS of the head and neck. Case 2, a male patient aged 85 years were admitted due to erythemalike hyperplasia in the left anterior head with necrosis and scar formation at the center for 2 months. He was misdiagnosed with folliculitis in another hospital, and histopathological examination confirmed the AS of the head and neck. Case 3, a male patient aged 87 years were admitted due to large erythema in the right scalp with ulcer and scar formation for 1 month, and histopathological examination confirmed the AS of the head and neck. One of them was lost to follow, one died 5 months after confirmed diagnosis, and one achieved favorable outcome after radiotherapy and received further follow up. The early clinical manifestations of the three patients were different and lacked characteristics. The disease progressed rapidly and the prognosis was poor. At present, surgery combined with postoperative radiotherapy is the preferred treatment. Through this article, the following conclusions can be obtained: erythema in the head and face of the elderly, rapid progresses and painful, pathological examinations must be performed, and changes in blood vessels and vascular endothelial cells with or without crack formation and red blood cell extravasation should be carefully observed during pathological examinations in case of misdiagnosis. It is hoped that these three cases can serve as a reminder for clinicians, for reducing misdiagnosis and miss diagnosis, choosing appropriate treatment methods, and judging their prognosis. Therefore, early diagnosis and surgical treatment are extremely important to improve the prognosis of AS patients.

Background The pathological basis of coronary artery disease (CAD) is atherosclerosis which is associated with inflammation and dyslipidemia. However, the involvement of hypersensitive C-reactive protein (hs-CRP) in lipid metabolism and how it affects the pathogenesis of CAD is uncertain. Objective To explore whether the relationship between dyslipidemia and CAD is partly mediated by hs-CRP levels. Methods Three hundred fifteen pairs of randomly sexand age-matched CAD and non-CAD subjects collected from Zhongda Hospital Affiliated to Southeast University were involved in the final analysis. We gathered information about each subjects clinical history as well as their results of detected hs-CRP and lipid levels. Linear regression analysis was used to determine the association between dyslipidemia and hs-CRP levels in which univariate and multivariate logistic regression analyzes were performed to determine the relationship between hs-CRP levels and CAD as well as dyslipidemia and CAD. Mediation analysis was used to evaluate whether hs-CRP levels act as a mediator of the relationship between dyslipidemia and CAD. Results Dyslipidemia and hs-CRP levels were significantly associated with an increased risk of CAD, with β = 0.594 (P = 0.001) and β = 0.016 (P = 0.024), respectively, and there was a correlation between dyslipidemia and hs-CRP levels (β = 3.273, P = 0.004). Mediation analysis results revealed that the correlation between dyslipidemia and CAD was 8.27% mediated by hs-CRP levels with a direct effect of 0.621 and an indirect effect of 0.056. Conclusion Hs-CRP levels played a partial mediation role in the association between dyslipidemia and CAD.

To compare the effects of acupuncture and moxibustion alone or in combination on the number of mast cells and expression levels of cytoketatin 18 (CK18) and CK19 (marker of Meckel cells), and calcitonin gene-related peptide (CGRP), neuropeptide-Y (NPY) and bradykinin (BK) in the local acupoint area of rats with chronic atrophic gastritis (CAG).Fifty male SD rats were randomly divided into normal, CAG model, moxibustion, acupuncture and acupuncture+moxi-bustion groups (10 rats in each group). The CAG model was established by gavage of 1-methyl-3-nitro-1-nitrosoguanidine (170 μg/mL,1 mL/100 g, once a week) and 40% ethanol solution (twice a week) for 12 consecutive weeks. After successful establishment of CAG model, moxibustion, manual acupuncture or acupuncture+moxibustion was applied to bilateral "Zusanli" (ST36) and "Zhongwan"(CV12) for 15 min, once daily for 14 consecutive days. At the end of the experiment, the gastric mucosal tissues were collected for observing histopathological changes of gastric mucosa after H.E. staining, and the tissues of the stimulated ST36 region collected for detecting the expression levels of CK18, CK19, CGRP, NPY and BK and the number of mast cells in the local ST36 region by immunohistochemistry.Compared with the normal group, the number of mast cells, the expression levels of CK19, NPY and BK in the ST36 area were significantly increased (Acupuncture combined with moxibustion of ST36 can up-regulate the levels of local CK18, CK19 and CGRP proteins and number of mast cells, moxibustion may up-regulate the levels of CGRP and NPY and number of mast cells, while acupuncture may up-regulate the expression of CGRP in the local stimulated area in CAG rats.

To summarize and elucidate the characteristics and evolvement of Chinese medicine (CM) patterns reflecting the physical and mental conditions of participants in the Mars 500 long-term closed environment. The DS01-T Digital TCM Four-Diagnostic Instrument and CM Inquiring Diagnostic Questionnaire were used to collect information from 6 participants in the Mars 500 International Joint Research Project, through diagnostic methods of observation, palpation and inquiry according to CM theory. During the 520 days of the experiment, data collection was performed 37 times; a total of over 400 digital images of tongues and facial complexion and over 20,000 data were collected. These data were then analyzed by a team of experts in CM, statistics, and data mining. The CM pattern evolvement of participants in the long-term closed environment followed some common trends. Qi deficiency was the main CM pattern observed, with individual features depending on constitutional differences [manifested in varying degrees of accompanying patterns of Gan (Liver) qi stagnation, Pi (Spleen) deficiency, dampness encumbering, or yin deficiency]. The research has verified the effectiveness of CM syndrome differentiation based on the four diagnostic methods, which should serve as a solid foundation for observation, monitoring, and intervention in regard to the health conditions of astronauts in long-term space flights in the future.

Sepsis is the leading cause of death in hospital intensive care units. In light of recent studies showing that variations in N6-methyladenosine (m6A) levels in different RNA transcripts influence inflammatory responses, we evaluated the m6A profiles of rat aortic mRNAs and lncRNAs after lipopolysaccharide (LPS)-induced sepsis. LC-MS-based mRNA modification analysis showed that global m6A levels were significantly decreased in aortic tissue of rats injected intraperitoneally with LPS. This finding was consistent with downregulated expression of METTL3 and WTAP, two members of the m6A writer complex, in LPS-exposed aortas. Microarray analysis of m6A methylation indicated that 40 transcripts (31 mRNAs and 9 lncRNAs) were hypermethylated, while 223 transcripts (156 mRNAs and 67 lncRNAs) were hypomethylated, in aortic tissue from LPS-treated rats. On GO and KEGG analyses, ‘complement and coagulation cascades’, ‘transient receptor potential channels’, and ‘organic anion transmembrane transporter activity’ were the major biological processes modulated by the differentially m6A methylated mRNAs. In turn, competing endogenous RNA network analysis suggested that decreased m6A levels in lncRNA-XR_343955 may affect the inflammatory response through the cell adhesion molecule pathway. Our data suggest that therapeutic modulation of the cellular m6A machinery may be useful to preserve vascular integrity and function during sepsis.

Background. We performed a network meta-analysis (NMA) comparing the efficacy (stroke or systemic embolism) and safety (major bleeding) among different non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and renal impairment, with the aim of recommending the proper drug and the dose based on renal function. Methods. We searched PubMed, EMBASE, Web of Science, and Cochrane Library with the items “dabigatran, edoxaban, apixaban, rivaroxaban, warfarin, and atrial fibrillation” through August 2019. NMA was analyzed with R (version 3.5.1, R Foundation for Statistical Computing) with the packages gemtc recalling JAGS (version 4.3.0) for the efficacy and safety of each drug with regard to different levels of renal function. NetMetaXL (version 1.6.1) and winBUGS (version 1.4.3) were used to obtain the cumulative ranking curve (SUCRA) of each drug. Result. In patients with normal renal function, dabigatran150 was ranked as the most effective drug (SUCRA 0.90), followed by dabigatran110 (SUCRA 0.68), apixaban (SUCRA 0.66), and rivaroxaban (SUCRA 0.59). With regard to the safety for preventing major bleeding, there was high probability that edoxaban30 (SUCRA 0.99) ranked first, compared to dabigatran110 (SUCRA 0.78) and edoxaban60 (SUCRA 0.66). For patients with mild renal impairment, with respect to the most effective drug for preventing stroke or systemic embolism, edoxaban60 ranked first (SUCRA 0.98), in comparison with dabigatran150 (SUCRA 0.74) and apixaban (SUCRA 0.64). Possibility of ranking first for the safest drug was edoxaban30 (SUCRA 0.99), followed by dabigatran110 (SUCRA 0.70) and apixaban (SUCRA 0.69). In patients with moderate renal function, dabigatran150 (SUCRA 0.95) ranked as the most effective drug in comparison with apixaban (SUCRA 0.66). Dabigatran110 (SUCRA 0.53), rivaroxaban (SUCRA 0.51), and edoxaban60 (SUCRA 0.50) had the similar probability of ranking third. When referred to the safest drug, probability of ranking first for preventing major bleeding was edoxaban30 (SUCRA 0.98), followed by apixaban (SUCRA 0.85) and edoxaban60 (SUCRA 0.64). Conclusion. In patients with AF and renal impairment and for patients with normal renal function, dabigatran 110 mg (bid) might have a better effect on the clinical results. And it does not coincide with patients taking dabigatran 110 mg with dose reduction for other factors including aged ≥75 years, renal impairment (CrCL 30–50 mL/min), gastritis, esophagitis, or gastroesophageal reflux, receiving concomitant verapamil, and so on. For patients with mild renal impairment, apixaban 5 mg (bid) would be a better choice for preventing stroke or systemic embolism and major bleeding, while apixaban 5 mg (bid) and edoxaban 60 mg (qd) were recommended for patients with moderate renal impairment. However, considering the fact of no RCTs for the head-to-head comparison, caution should be exercised over selecting each of NOACs for patients.

Background CT advances allow coronary arterial tree to be entirely covered during one CTP scan. Our aim was to investigate the potential value of single-phase coronary CT angiography (SP-CCTA) extracted from stress dynamic myocardial CT perfusion (CTP) for coronary artery stenosis assessment. Methods Consecutive symptomatic patients were prospectively recruited and scanned with an ATP-stress dynamic myocardial CTP and routine CCTA protocol using third-generation DSCT. Noise reduction was applied to optimize image quality (IQ), the CTP phase with the best enhancement of the coronary arteries was selected as the SP-CCTA. IQ was assessed qualitatively. Using coronary angiography (CAG) as the reference standard, the diagnostic performance for stenosis detection was compared for SP-CCTA and routine CCTA. Results 56 patients underwent the CTP and CCTA examination, among which 39 patients underwent CAG. The qualitative IQ scores of SP-CCTA were similar to that of routine CCTA (p > 0.05). On a per-segment basis, the sensitivity, specificity, positive predictive value, negative predictive value, diagnostic accuracy and area under the receiver-operating-characteristic curve results of SP-CCTA and routine CCTA for diagnosis of stenosis ≥50% exhibited no significant difference (SP-CCTA: 78.1%, 94.9%, 77.4%, 95.1%, 91.6% and 0.935 vs. routine CCTA: 74.7%, 95.3%, 78.0%, 95.3%, 91.6% and 0.937; all p > 0.05). The mean effective radiation dose of CTP and routine CCTA plus CTP were 3.92 ± 1.72 mSv and 5.98 ± 2.01 mSv (p Conclusions The IQ and diagnostic value of SP-CCTA was equivalent to routine CCTA on third-generation DSCT. SP-CCTA images from CTP may potentially replace a separate routine CCTA, allowing the possibility of “one-stop” cardiac examination for high-risk CAD patients who need myocardial ischemia assessment.

The cerebrospinal fluid (CSF)-contacting nucleus is implicated in the descending inhibitory pathway in pain processing, whereas the cellular and molecular mechanisms underpinning CSF-contacting nucleus regulating pain signals remains largely elusive. ATP is evidenced to inhibit pain transmission at supraspinal level by the mediation of the receptor P2X, wherein its subtype P2X3 is identified as the most potent. Our present experiment investigated the functionality of P2X3 receptors in CSF-contacting nucleus in the formalin-evoked inflammatory pain. Immunofluorescence and western blot revealed the expression of P2X3 receptors in the CSF-contacting nucleus and their upregulated expression subsequent to administration of formalin in rat model. ATP (a P2X3 receptor agonist, 100nmol/5µl) by intracerebroventricular (i.c.v.) administration ameliorated pain behaviors and enhanced c-Fos immunoreactivity in the neurons of the periaqueductal gray (PAG), both of which were discounted by pre-administration of A-317491 (a selective P2X3 receptor antagonist, 25nmol/5µl). After the CSF-contacting nucleus was ablated by cholera toxin subunit B-saporin, ATP failed to induce analgesia, with the c-Fos immunoreactivity in the PAG neurons remaining intact. Our results validated that P2X3 receptors in the CSF-contacting nucleus are pivotal in inflammatory pain processing via the activation of PAG neurons.

To investigate oral health status in the residents of Sichuan Province, southwest China, a cross-sectional study was performed using the latest Oral Health Survey Basic Methods recommended by the World Health Organization. A multistage stratified random cluster-sampling method was used to enroll participants from the following three groups: children aged 3–5 years, adolescents aged 12 years, and people aged 65–74 years. In these three groups, the mean numbers of teeth that were affected by caries were 3.28, 0.86 and 5.13, respectively, resulting in a prevalence of 63.47%, 37.20% and 83.20%, respectively. Relative to the high rate of decayed teeth, the prevalence of fillings was very low in all age groups (0.97%, 7.24% and 5.43%, respectively). In the 12-year-old adolescent group, only 3.61% had good pit and fissure sealing. In addition, the rate of dental fluorosis was 24.80%, and the Community Fluorosis Index value was 0.39. In the elder group, the community periodontal index was 2.92. The prevalence in the elderly of having lost at least one tooth was 75.54%. Additionally, 4.44% of these participants were edentulous. The incidence of dental prosthesis was 51.75%, the proportion with a removable partial denture, a fixed denture, full dentures, dental implants and an informal fixed bridge was 21.59%, 11.45%, 4.64%, 0 and 16.67%, respectively. In this study, 8.2% of the elderly participants were affected by different types of oral mucosal lesions. Among such lesions, recurrent aphthous ulcers were most prevalent (2.69%) and oral lichen planuses were second (1.6%). The conclusion presented in this survey is that oral diseases, especially dental caries and periodontal disease, are frequent and common in Sichuan province, China. Moreover, the treatment rate is very low, and primary prevention and treatment options are therefore urgently needed in this population. A survey of over 8 000 residents from Sichuan in China found evidence of poor oral health, especially dental caries and periodontal disease. The study, led by Tao Hu and Xuedong Zhou of Sichuan University, looked at teeth, gums and oral mucosa in three age groups: 3–5 years, 12 years, and 65–74 years. The examinations were performed using World Health Organization guidelines designed to promote international comparison. Despite significant improvements in recent years, oral disease in multiple forms was still highly prevalent in all age ranges, with rural areas suffering from poor disease prevention and treatment. The elderly had a particularly high prevalence of disease. The results of the survey provide strong evidence that improvement of oral health requires prioritization by local authorities.

AIM To investigate the association between serum human epidermal growth factor receptor 2 (HER2) extracellular domain (ECD) and tissue HER2 status, and the prognostic value of serum HER2 ECD in patients with gastric cancer. METHODS A total of 239 patients with gastric cancer were enrolled from December 2012 to June 2013. Serum HER2 ECD was determined by chemiluminescent assay, and tissue HER2 status was evaluated by immunohistochemistry and fluorescence in situ hybridization assay. A receiver operating characteristic (ROC) curve was plotted to identify the optimal cut-off value for serum HER2 ECD assay for predicting survival in gastric cancer patients. RESULTS Serum HER2 ECD was significantly correlated with tissue HER2 status (P < 0.001), tumor size (P < 0.001), and intestinal type of gastric cancer (P = 0.021). Serum HER2 ECD levels differed significantly between patients with HER2-positive tissue expression and those with HER2-negative tissue expression. ROC analysis yielded an area under the curve value of 0.79 (95%CI: 0.71-0.87, P < 0.001), with a sensitivity and specificity of 0.54 (95%CI: 0.37-0.70) and 0.93 (95%CI: 0.88-0.96), respectively. With a cut-off value of 24.75 ng/mL, high serum HER2 ECD had a negative impact on overall survival of the patients (HR: 1.93, 95%CI: 1.32-4.38, P = 0.006). CONCLUSION Serum HER2 ECD could be a highly specific surrogate biomarker for tissue HER2 status in gastric cancer. Optimal cut-off criteria for predicting survival should be established.

Background Previous studies have shown that DNA methylation plays a significant role in myelodysplastic syndrome (MDS). In addition to hypermethylation, aberrant hypomethylation can result in the transcriptional activation of oncogenes in cancer, including MDS. Therefore, drugs targeting DNA hypomethylation are needed for the treatment of MDS. This study aimed to investigate whether As2S2 promoted hypomethylation by increasing DNA methyltransferases (DNMTs) expression in MDS. Patients and Methods Ten bone marrow samples from MDS patients and 3 healthy donors were obtained for the examination of the DNA methylation with a Human Methylation 850K Bead Chip. The mRNA expressions for the DNMTs in the ten MDS patients and 3 controls were compared by Q-PCR. Then, the MDS cell line SKM-1 was treated with As2S2. After 2 days of treatment, Human Methylation 850K Bead Chip was applied to analyze the changes of gene methylation status in the cells. Q-PCR and Western blot were taken to test the changes of mRNA and protein expressions for DNMTs in SKM-1 cells after treatment. Results Five hundred ninety-two abnormally hypomethylated genes were found in MDS patients compared to those in controls by Human Methylation 850K. The mRNA expressions of DNMTs (DNMT1, DNMT3a and DNMT3b) in MDS patients were significantly lower than those in healthy individuals. The IC50 value of As2S2 for SKM-1 cells was 4.97 μmol/L.Treatment with As2S2 at 2 μmoL/L resulted in significant alterations in the methylation levels at 1718 sites in SKM-1 cells compared to those in the controls. Hypermethylation was observed in 1625 sites (94.58%), corresponding to 975 genes, compared to those in the controls. Finally, the expression levels of DNMTs (DNMT1, DNMT3a, and DNMT3b) significantly increased in SKM-1 cells treated with As2S2 at 2 μmoL/L and 4 μmoL/L. Conclusion These data show a potential clinical application of As2S2 as an innovative hypermethylation agent in MDS.

The present systematic review determined the role of transarterial embolization (TAE) as a prophylactic treatment in bleeding peptic ulcers after initial successful endoscopic hemostasis. PubMed and Ovid Medline databases were searched from inception until July 2019 for studies that included patients deemed high-risk based on Forrest Classification, Rockall score ≥ 5, or endoscopic evaluation in addition to those who underwent prophylactic TAE after initial successful endoscopic hemostasis. Meta-analysis was performed to compare patients who underwent endoscopic therapy (ET) and TAE with those who underwent ET alone. The primary outcomes measured included rates of rebleeding, reintervention, and 30-day mortality. Secondary outcome measures evaluated length of hospitalization, technical success rates, and complications associated with TAE. Of 916 publications, 5 were eligible for inclusion; 310 patients with high-risk peptic ulcer bleeding underwent prophylactic TAE, and 255 were compared against a control group of 580 patients that underwent standard treatment with ET alone. Patients who underwent ET with TAE had lower 30-day rebleeding rates (odds ratio [OR], 0.35; 95% confidence interval [CI] 0.15–0.85; P = .02; I2 = 50%). The ET with TAE group had a lower 30-day mortality rate (OR, 0.28; 95% CI, 0.10–0.83; P = .02; I2 = 58%). There was no difference in pooled reintervention rates (OR, 0.68; 95% CI, 0.43–1.08; P = .10; I2 = 0%) and length of hospitalization (mean difference, −0.32; 95% CI, −1.88 to 1.24; P = .69; I2 = 0%). Technical success rate of prophylactic TAE was 90.5% (95% CI, 83.09–97.98; I2 = 75.9%). Pooled proportion of overall complication rate was 0.18% (95% CI, 0.00–1.28; I2 = 0%). Prophylactic TAE has lower rebleeding and mortality with a good success rate and low complications. Prophylactic TAE after primary ET may be recommended for selected patients with high-risk bleeding ulcers; however, further studies should be performed to establish this as a routine tool in patients with bleeding peptic ulcer disease.

Abnormal expression of microRNAs (miRNAs) is involved in the development of and anti‑apoptotic effects in various types of human cancer. However, miRNA‑mediated regulation of oral verrucous carcinoma (OVC) remains to be elucidated. The present study aimed to investigate the expression of miR‑181b in OVC and oral squamous cell carcinoma (OSCC). The expression levels of miR‑181b were determined using reverse transcription‑quantitative polymerase chain reaction. The expression levels of B‑cell lymphoma 2 (Bcl‑2) and leucine rich repeats and immunoglobulin like domains 1 (LRIG1), were evaluated using immunohistochemical staining. The correlation between Bcl‑2 and LRIG1 expression was determined using a Pearson correlation analysis. The expression levels of miR‑181b and Bcl‑2 in OVC were significantly higher compared with normal mucosal tissue (NM); however, lower compared with the OSCC. The key target of miR‑181b was LRIG1 and it was significantly lower in OVC tissues compared with NM tissue; however this was higher when compared with OSCC tissue. The expression levels of Bcl‑2 were correlated with expression levels of LRIG1 in OVC tissues. Therefore, LRIG1 may be associated with anti‑apoptotic function in OVC tissues.

// Shuang Zhao 1 , Xue-feng Yang 1 , Dao-fu Shen 1 , Yang Gao 1 , Shuai Shi 1 , Ji-cheng Wu 1 , Hong-xu Liu 2 , Hong-zhi Sun 1 , Rong-jian Su 3 , Hua-chuan Zheng 1, 3 1 Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Animal Center, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, China 2 Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China 3 Life Science Institute of Jinzhou Medical University, Jinzhou, 121001, China Correspondence to: Hua-chuan Zheng, email: zheng_huachuan@hotmail.com Keywords: lung cancer, ING5, pathogenesis, aggressiveness, prognosis Received: February 06, 2016 Accepted: May 28, 2016 Published: July 09, 2016 ABSTRACT ING5 can interact with p53, thereby inhibiting cell growth and inducing apoptosis. We found that ING5 overexpression not only inhibited proliferation, migration, and invasion, but also induced G2 arrest, differentiation, autophagy, apoptosis, glycolysis and mitochondrial respiration in lung cancer cells. ING5 transfection up-regulated the expression of Cdc2, ATG13, ATG14, Beclin-1, LC-3B, AIF, cytochrome c, Akt1/2/3, ADFP, PFK-1 and PDPc, while down-regulated the expression of Bcl-2, XIAP, survivin,β-catenin and HXK1. ING5 transfection desensitized cells to the chemotherapy of MG132, paclitaxel, and SAHA, which paralleled with apoptotic alteration. ING5 overexpression suppressed the xenograft tumor growth by inhibiting proliferation and inducing apoptosis. ING5 expression level was significantly higher in normal tissue than that in lung cancer at both protein and mRNA levels. Nuclear ING5 expression was positively correlated with ki-67 expression and cytoplasmic ING5 expression. Cytoplasmic ING5 expression was positively associated with lymph node metastasis, and negatively with age, lymphatic invasion or CPP32 expression. ING5 expression was different in histological classification: squamous cell carcinoma > adenocarcinoma > large cell carcinoma > small cell carcinoma. Taken together, our data suggested that ING5 downregulation might involved in carcinogenesis, growth, and invasion of lung cancer and could be considered as a promising marker to gauge the aggressiveness of lung cancer. It might be employed as a potential target for gene therapy of lung cancer.

Although Butylphthalide (BP) has protective effects that reduce ischemia-induced brain damage and neuronal cell death, little is known about the precise mechanisms occurring during cerebral ischemia/reperfusion (I/R). Therefore, the aim of this study was to investigate the neuroprotective mechanisms of BP against ischemic brain injury induced by cerebral I/R through inhibition of the c-Jun N-terminal kinase (JNK)-Caspase3 signaling pathway. BP in distilled non-genetically modified Soybean oil was administered intragastrically three times a day at a dosage of 15 mg/(kg day) beginning at 20 min after I/R in Sprague-Dawley rats. Immunohistochemical staining and Western blotting were performed to examine the expression of related proteins, and TUNEL-staining was used to detect the percentage of neuronal apoptosis in the hippocampal CA1 region. The results showed that BP could significantly protect neurons against cerebral I/R-induced damage. Furthermore, the expression of p-JNK, p-Bcl2, p-c-Jun, FasL, and cleaved-caspase3 was also decreased in the rats treated with BP. In summary, our results imply that BP could remarkably improve the survival of CA1 pyramidal neurons in I/R-induced brain injury and inhibit the JNK-Caspase3 signaling pathway.

Risky decisions are ubiquitous in daily life and are central to human behavior, but little attention has been devoted to exploring whether risky choice can be influenced by gaze direction. In the current study, we used gaze-contingent manipulation to manipulate an individual's gaze while he/she decided between two risky options, and we examined whether risky decisions could be biased toward a randomly determined target. We found that participants' risky choices were biased toward a randomly determined target when they were manipulated to gaze longer at the target option (Study 1, N=37; Study 3, N=40) or at the target outcome dimension (Study 2, N=37). We also found that both the relative time advantage and the location of the last fixation mediated the effect of the gaze-contingent manipulation on risky choice in the valid trials. However, the mediation effects of the relative time advantage and the location of the last fixation were not significant when timed-out trials were included in Studies 2 and 3, indicating that the gaze-contingent manipulation did not effectively enforce a bias toward attending to a particular stimulus through eye gaze in all trials. Future work is needed to improve the effectiveness of the gaze-contingent prompt procedure.

To explore the possible long-term health effects of the defoamer used in seawater desalination by sub-chronic toxicity testing.Blood analysis, internal organ assessment, and histopathological examination were carried out in rats exposed to low, medium, and high (0.5, 1.0, and 2.0 g/kg BW, respectively) doses of defoamer for 90 days through oral administration.The high dose group showed decreased blood alanine aminotransferase and aspartate aminotransferase (P0.05). All doses resulted in a significant increase in albumin and decrease in globulin (P0.05). The direct bilirubin and indirect bilirubin were decreased in the medium and high dose groups (P0.05). All dose groups showed significant induction of alkaline phosphatase (P0.05). Pathological examination revealed a case of liver mononuclear cell infiltration in the medium dose group and three cases of liver congestion, steatosis of hepatic cells around the central vein, and punctate necrosis with multiple focal mononuclear cell infiltration in male rats administered the high dose. The No Observed Adverse Effect Level was 0.5 g/kg BW in rats, with albumin and total bilirubin as health effect indices.Long-term defoamer exposure may cause liver injury but has no significant impact on renal function in rats. The effect on blood cells in female rats was more prominent than that in male rats.

Objective The aim of this study was to investigate the effects of hyperbaric oxygen on the permeability of the blood-brain barrier in rats with global cerebral ischemia/reperfusion injury and explore possible mechanisms. Methods A rat model of global cerebral ischemia/reperfusion injury established via Pulsinelli four-vessel occlusion method and a total of 162 Wistar rats were randomly divided into three groups, including sham group, global cerebral ischemia/reperfusion group (IR group) and hyperbaric oxygen treated group (HBO group). Permeability of the blood-brain barrier of these rats were evaluated by Evans Blue staining. The expression of caveolin-1 and tight junction protein ZO-1 was examined by Immunohistochemistry staining and western-blotting. Results Successfully establishment of the rat model was verified by W:D ratio, and significantly increased Evans Blue level was found in IR group compared to control group, whereas hyperbaric treatment could result in decreased Evans Blue level in HBO group. Increased expression of caveolin-1 and tight junction protein ZO-1 were found in rats with hyperbaric oxygen exposure compared to those in IS group. Conclusions Hyperbaric oxygen exposure improved the permeability of the blood-brain barrier in rats with global cerebral ischemia/reperfusion injury, and increased expression of caveolin-1 and tight junction protein ZO-1 were involved in the mechanisms.

Cancer patients undergoing surgery are at high risk of venous thromboembolism (VTE). The occurrence of VTE in Chinese cancer patients admitted to intensive care unit (ICU) for postoperative care is poorly characterized. This study was designed to investigate the incidence of VTE in this population and to evaluate the utility of the Caprini score in risk stratification.2127 consecutive adult patients admitted to a 10-bed surgical ICU (SICU) in a tertiary care academic hospital during a 4-year period (January 1, 2013 - December 31, 2016) were enrolled. Demographic and VTE data were collected. Data for the Caprini risk assessment model (RAM) was used to stratify patients on their risk of VTE.Of the 2127 patients admitted to ICU after cancer surgery, 66 (3.1%) developed symptomatic VTE. There were a total of 32 patients with pulmonary embolism (PE), 51 patients with deep vein thrombosis (DVT) and 17 patients with both conditions. Based on the original Caprini RAM, 99.5% of the patients scored in the "highest risk" category (score ≥5), all patients with VTE were in the "highest risk" category. Further substratification in the "highest risk" category showed the risk of developing VTE events was significantly higher among patients with Caprini score greater than 10, as compared with patients with Caprini score of 5 to 6 (OR 5.63;95%CI 1.27-24.94), 7 to 8 (OR 2.36;95%CI 1.23-4.52 ) or 9 to 10 (OR 2.28;95%CI 1.17-4.44). The percentage of patients receiving double prophylaxis was 16.8% (358/2127), 20 of the 66 VTE patients (30.3%) received double prophylaxis before VTE was diagnosed. Patients with higher Caprini score were more likely to receive double thromboprophylaxis than patients with lower Caprini score (23.4% of patients with Caprini score10 vs 10.8% with Caprini score 5-6).Though accompanied with the subutilizing of chemoprophylaxis, the overall incidence of VTE was relatively low in Chinese cancer patients admitted to ICU for postoperative care. In contrast, the Caprini score was high in this population. The original Caprini RAM was limited to stratify this population, but further substratification of "highest risk" category demonstrated the risk of developing VTE events was significantly higher in patients with Caprini score greater than 10. Future research with high quality evidence should be performed targeting on the accurate risk stratification and optimizing VTE prophylaxis for this population.

Background Hepatic percutaneous microwave ablation (MWA) is usually performed in patients under conscious sedation. Nonetheless, many patients reported pain during the procedure. The current study investigated the safety and effectiveness of analgesia given at personalized dosage during the MWA procedure. Methods A total of 100 patients with hepatocellular carcinomas (HCCs) were included in this study. These patients underwent CT-guided percutaneous MWA between February and October 2017. Patients were randomized into two groups: Experimental group (n = 50) and Control group (n = 50). Patients in the Control group were given 5 mg of morphine intravenously, followed by 10 mg of morphine injected subcutaneously 30 min before surgery. Patients in the Experimental group were given a personalized dosage of morphine during the procedure when the Visual Analogue Scale (VAS) was ≥4. Other clinical and treatment parameters were also analysed. Results A significantly less amount of morphine (p

Accumulating evidence reveals that lipopolysaccharide (LPS) can induce neuroinflammation, ultimately leading to cognitive deficits. Mangiferin, a natural glucoxilxanthone, is known to possess various biological activities. The present study aimed to investigate the effects of mangiferin on LPS-induced cognitive deficits and explore the underlying mechanisms. Brain injury was induced in mice via intraperitoneal LPS injection (1mg/kg) for five consecutive days. Mangiferin was orally pretreatmented (50mg/kg) for seven days and then treatmented (50mg/kg) for five days after LPS injection. The Morris water maze was used to detect changes in cognitive function. Immunohistochemical and immunoblotting were respectively performed to measure the expression of interleukin-6 (IL-6) and heme oxygenase-1 (HO-1) in the hippocampus. The results showed that mangiferin can ameliorate cognitive deficits. Moreover, mangiferin decreased LPS-induced IL-6 production and increase HO-1 in the hippocampus. Taken together, these results suggest that mangiferin attenuates LPS-induced cognitive deficits, which may be potentially linked to modulating HO-1 in the hippocampus.

The aim of this study was to evaluate whether periodontal treatment in patients with periodontitis and hyperlipidemia may have any influence on plasma lipids and pro-inflammatory cytokine levels. We randomly assigned 109 patients with hyperlipidemia and chronic periodontitis into group 1 (n = 55) and group 2 (n = 54). Patients in group 1 underwent a standard cycle of supragingival mechanical scaling and polishing. Patients in group 2 underwent the adjunctive full-mouth intensive removal of subgingival dental plaque biofilms with the use of scaling and root planning. Periodontal parameters, total cholesterol (TC), triglyceride (TRG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-alpha (TNF-α), interleukin(IL)-1β(IL-1β), and IL-6 were evaluated before treatment and 2 and 6 months after treatment. Two and 6 months after treatment, TRG levels were significantly lower in group 2 than in group 1 (P

Objectives: In 2005, China acceded to the World Health Organization Framework Convention on Tobacco Control (WHO FCTC), the foundation for the global fight against tobacco. Certain cities in China have established local regulations to control tobacco use ahead of national policy, however, without the enforcement of statutory law, some of these regulations are merely lip service. The aim of the study was to assess the effects of city policy on smoking prevalence and on second-hand smoke (SHS) exposure status among non-smokers in Changchun City. Methods: A cross-sectional survey covering a multiple-stage, representative sample of the urban population aged ≥15 years was conducted between 1 Dec 2013 and 31 Jan 2014. The WHO and the US Centers for Disease Control and Prevention developed the questionnaires used, which included demographic characteristics, smoking behaviors and SHS exposure status. Results: Overall cigarette smoking prevalence was 23.5%, daily cigarette smoking prevalence was 21.2%. Smoking prevalence and cigarettes consumed per day was higher among men (p &lt, 0.05) and those aged 45–64 years (p &lt, 0.05). Among current smokers, 8.1% planned to quit within 12 months, 53.4% had no intention of quitting. Overall SHS exposure prevalence was 41.9% (workplace) and 34.1% (at home) over the previous 30 days. The weighted workplace SHS exposure prevalence increased with age. Conclusions: The high proportion of smokers with no intention of quitting and the high level of SHS exposure may constitute one of the most significant barriers to successful smoking cessation in the city. A continued drive to promote full implementation of the WHO FCTC is still needed.

// Hua-chuan Zheng 1 , Jing Li 2 , Dao-fu Shen 1 , Xue-feng Yang 1 , Shuang Zhao 1 , Ya-zhou Wu 1 , Yasuo Takano 3 , Hong-zhi Sun 1 , Rong-jian Su 4 , Jun-sheng Luo 1 , Wen-feng Gou 1 1 Cancer Research Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal Center, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China 2 Department of Gastroenterology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, China 3 School of Health Science, Tokyo University of Technology, Ohta-ku, Tokyo, Japan 4 Experimental Center, Liaoning Medical University, Jinzhou, China Correspondence to: Wen-feng Gou, e-mail: xiaogouaeiou@163.com Keywords: gastric cancer, BTG1, pathobiological behaviors, carcinogenesis, gene therapy Received: March 11, 2015 Accepted: May 23, 2015 Published: June 05, 2015 ABSTRACT Here, we found that BTG1 overexpression inhibited proliferation, migration and invasion, induced G 2 /M arrest, differentiation, senescence and apoptosis in BGC-823 and MKN28 cells ( p < 0.05). BTG1 transfectants showed a higher mRNA expression of Cyclin D1 and Bax , but a lower mRNA expression of cdc2, p21, mTOR and MMP-9 than the control and mock ( p < 0.05). After treated with cisplatin, MG132, paclitaxel and SAHA, both BTG1 transfectants showed lower mRNA viability and higher apoptosis than the control in both time- and dose-dependent manners ( p < 0.05) with the hypoexpression of chemoresistance-related genes ( slug , CD147 , GRP78 , GRP94 , FBXW7 TOP1 , TOP2 and GST-π ). BTG1 expression was restored after 5-aza-2′-deoxycytidine treatment in gastric cancer cells. BTG1 expression was statistically lower in gastric cancer than non-neoplastic mucosa and metastatic cancer in lymph node ( p < 0.05). BTG1 expression was positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, TNM staging and worse prognosis ( p < 0.05). The diffuse-type carcinoma showed less BTG1 expression than intestinal- and mixed-type ones ( p < 0.05). BTG1 overexpression suppressed tumor growth and lung metastasis of gastric cancer cells by inhibiting proliferation, enhancing autophagy and apoptosis in xenograft models. It was suggested that down-regulated BTG1 expression might promote gastric carcinogenesis partially due to its promoter methylation. BTG1 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of gastric cancer.

Here, we found that ING5 overexpression increased autophagy, differentiation, and decreased proliferation, apoptosis, migration, invasion and lamellipodia formation in gastric cancer cells, while ING5 knockdown had the opposite effects. In SGC-7901 transfectants, ING5 overexpression caused G1 arrest, which was positively associated with 14-3-3 overexpression, Cdk4 and c-jun hypoexpression. The induction of Bax hypoexpression, Bcl-2, survivin, 14-3-3, PI3K, p-Akt and p70S6K overexpression by ING5 decreased apoptosis in SGC-7901 cells. The hypoexpression of MMP-9, MAP1B and flotillin 2 contributed to the inhibitory effects of ING5 on migration and invasion of SGC-7901 cells. ING5 overexpression might activate both β-catenin and NF-κB pathways in SGC-7901 cells, and promote the expression of down-stream genes (c-myc, VEGF, Cyclin D1, survivin, and interleukins). Compared with the control, ING5 transfectants displayed drug resistance to triciribine, paclitaxel, cisplatin, SAHA, MG132 and parthenolide, which was positively related to their apoptotic induction and the overexpression of chemoresistance-related genes (MDR1, GRP78, GRP94, IRE, CD147, FBXW7, TOP1, TOP2, MLH1, MRP1, BRCP1 and GST-π). ING5 expression was higher in gastric cancer than matched mucosa. It was inversely associated with tumor size, dedifferentiation, lymph node metastasis and clinicopathological staging of cancer. ING5 overexpression suppressed growth, blood supply and lung metastasis of SGC-7901 cells by inhibiting proliferation, enhancing autophagy and apoptosis in xenograft models. It was suggested that ING5 expression might be employed as a good marker for gastric carcinogenesis and subsequent progression by inhibiting proliferation, growth, migration, invasion and metastasis. ING5 might induce apoptotic and chemotherapeutic resistances of gastric cancer cells by activating β-catenin, NF-κB and Akt pathways.

BACKGROUND Aberrant expression of defensins is implicated in the pathogenesis of digestive diseases. However, the contribution of specific defensins and the influence of their genetic polymorphisms on the progression of digestive diseases remain controversial. In the present meta-analysis, we investigated the association between DEFB1 SNPs and the susceptibility to digestive diseases. MATERIAL AND METHODS Case-control studies that reported the correlation between DEFB1 SNPs and the susceptibility to digestive diseases were identified through electronic databases searches, and high-quality studies that satisfied our inclusion criteria were selected for this meta-analysis. Statistical analyses were performed utilizing STATA software version 12.0. RESULTS The present meta-analysis revealed that patients with digestive diseases exhibited higher frequencies of the DEFB1 genetic variants rs11362G>A, rs1800972C>G, and rs1799946G>A compared to healthy controls under the allele model. Subgroup analysis based on country showed that the rs1800972C>G variant under allele model and rs1799946G>A are associated with the susceptibility to digestive diseases in Hungarian and Italian populations, respectively. Subgroup analysis based on disease type showed that: (1) rs11362G>A variant was strongly associated with severe acute pancreatitis (SAP) and chronic gastritis, (2) frequency of rs1800972C>G variant was higher in SAP subgroup, and (3) frequency of rs1799946G>A variant was positively associated with the susceptibility to Crohn's disease (CD) under the allele model and with SAP. CONCLUSIONS Our meta-analysis provides evidence that DEFB1 genetic polymorphisms rs11362G>A, rs1800972C>G and rs1799946G>A are important contributing factors to the development of digestive diseases.

Supplemental Digital Content is available in the text, Background: Stroke is a condition with high morbidity and mortality, and 75% of stroke survivors lose their ability to work. Stroke is a burden to the family and society. The purpose of this study was to evaluate the effectiveness of Chinese herbal patent medicines in the treatment of patients after the acute phase of a stroke. Methods: We searched the following databases through August 2016: PubMed, Embase, Cochrane library, China Knowledge Resource Integrated Database (CNKI), China Science Periodical Database (CSPD), and China Biology Medicine disc (CBMdisc) for studies that evaluated Chinese herbal patent medicines for post stroke recovery. A random-effect model was used to pool therapeutic effects of Chinese herbal patent medicines on stroke recovery. Network meta-analysis was used to rank the treatment for each Chinese herbal patent medicine. Results: In our meta-analysis, we evaluated 28 trials that included 2780 patients. Chinese herbal patent medicines were effective in promoting recovery after stroke (OR, 3.03; 95% CI: 2.53–3.64; P

The minichromosomal maintenance (MCM) proteins are involved in the initiation and DNA replication. The role of MCM4 remains to be elucidated. The purpose of this study was to investigate the effects of MCM4 in laryngeal squamous cell carcinoma (LSCC) cell growth and apoptosis.LSCC cell line UMSCC 5 was used in this study. The small interfering RNA (siRNA) of MCM 4 gene was used to identify the effects of MCM4 on the proliferation and apoptosis using methylimidazole tetrazolium (MTT) assay and flow-cytometry, respectively. Confirmed LSCC and adjacent non-tumor tissues were collected from 34 patients who were willing to participate in the study, from 2010 through 2015, from 163 patients undergoing treatment in the Department of Otorhinolaryngology/Head and Neck Surgery of Beijing Tongren Hospital in Capital Medical University of P.R. China. Immunohistochemical staining of MCM4 expression in the resected tissues was performed to analyze the correlation between its expression and the clinicopathological characteristics.The results showed that siRNA of MCM4 could significantly inhibit LSCC cell line UMSCC 5 proliferation and induce apoptosis. MCM4 mRNA was higher expressed in carcinoma tissues than in adjacent normal tissues. MCM4 expression was correlated with male gender, smoking history and poor differentiation.We noticed a significant role for MCM4 overexpression in human LSCC tissues and their corresponding adjacent non-neoplastic tissues and found that siRNA of MCM4 can significantly decrease the proliferation of cancer cells. It is suggested that MCM4 profiling could potentially be used to predict response to treatment and prognosis in LSCC.

To investigate the efficacy, advantages and disadvantages of internal and external elbow joint approach and olecranon osteotomy approach for the treatment of intercondylar fracture of humerus.From October 2012 to May 2016, 18 cases of intercondylar fracture of humerus were treated by operation including 12 males and 6 females with a mean age of 33.5 years old (ranged from 4 to 56 years old); 8 cases were operated by internal and external elbow joint approach, 10 cases were operated by olecranon osteotomy approach. According to AO classification, 3 cases were type C1, 8 cases were type C2, 7 cases were type C3. All patients were excluded from neurologic and vascular injuries.All patients were followed up from 12 to 26 months with an average of 15 months. The incision healed well and no heterotopic ossification was found. According to the modified Cassebaum elbow function score, the result was excellence in 14 cases, good in 3 cases, fair in 1 case.According to the fracture type, the appropriate surgical approach and fixation were selected in order to get anatomic reduction. Rigid fixation, and early functional exercise is important condition for successful operation and satisfactory functional recovery in intercondylar fracture of the humerus.

In order to study the application of antibodies against recombinant proteins for detecting Borna disease virus (BDV) phosphoprotein (p24) and nucleoprotein (p40) (BDV‑p24/p40) on paraffin sections by immunohistochemistry. The purified fusion p24 and p40 proteins were used for the preparation of polyclonal and monoclonal anti‑p24 and anti‑40 antibodies, which were confirmed by ELISA and western blotting. Paraffin sections were made from BDV‑infected Sprague‑Dawley (SD) rats (n=20), PBS‑injected SD rats (n=20), normal SD rats (n=20) and normal C57 mice (n=20). Immunohistochemical staining was performed according to the EnVision™ two‑step protocol. Heat‑mediated antigen retrieval was performed using the retrieval buffer sodium citrate (1 mM; pH 6.0). All the antibodies against recombinant proteins exhibited good sensitivity and specificity. There were significant differences between the BDV‑infected group and the BDV‑uninfected group for poly‑ and monoclonal anti‑p24 and ‑p40 antibodies. These antibodies against recombinant proteins may be used effectively to detect BDV p24 and p40 in paraffin sections.

To evaluate the potential risk of arteriosclerosis caused by desalinated seawater, Wistar rats were provided desalinated seawater over a 1-year period, and blood samples were collected at 0, 90, 180, and 360 days. Blood calcium, magnesium, and arteriosclerosis-related indicators were investigated. Female rats treated with desalinated seawater for 180 days showed lower magnesium levels than the control rats (P0.05). The calcium and magnesium levels in female rats and the magnesium level in male rats were lower than the levels in the controls, following treatment with desalinated seawater for 360 days (P0.05). Blood levels of arteriosclerosis-related lipid peroxidation indicators and C-reactive protein (CRP) in the treatment group did not differ from those in the controls. The levels of lipid peroxidation indicators and CRP in rats were not significantly affected by drinking desalinated seawater, and no increase in risk of arteriosclerosis was observed.

No randomized comparative trials have presented long-term outcomes for laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). The present study was designed to compare the efficacy and safety of these two procedures. From January 2007 to July 2008, 64 eligible patients were randomly assigned to LSG or LRYGB. During the 5-year follow-up, we compared morbidity rate, body mass index (BMI), percent of excess weight loss (%EWL), Moorehead-Ardelt (M-A) II quality of life, and resolution or improvement rate of obesity-related comorbidities between the groups. Both groups were matched with respect to age, gender, and BMI. Slightly more major complications were observed in patients undergoing LRYGB (P > 0.05). Weight loss was significantly better with LRYGB except during the first postoperative year. At 5 years, %EWL for LSG and LRYGB was 63.2 ± 24.5 % and 76.2 ± 21.7 % (P = 0.02), respectively. No statistical difference was observed in quality of life between the groups at all intervals (P > 0.05). At the last follow-up, most comorbidities in both groups were resolved or improved, with no difference between the groups (P > 0.05). LRYGB and LSG are equally safe and effective in quality of life and improvement or resolution of comorbidities, and LRYGB possesses the superiority in terms of weight loss. Further studies are needed to evaluate micronutrient deficiencies of these procedures.

Mangiferin has been extensively applied in different fields due to its anti-inflammatory properties. However, the precise mechanism used by mangiferin on lipopolysaccharide (LPS)-induced inflammation has not been elucidated. Here, we discuss the potential mechanism of mangiferin during a LPS-induced brain injury. Brain injury was induced in ICR mice via intraperitoneal LPS injection (5 mg/kg). Open- and closed-field tests were used to detect the behaviors of mice, while immunoblotting was performed to measure the expression of interleukin-6 (IL-6) and cystathionine-b-synthase (CBS) in the hippocampus after mangiferin was orally administered (p.o.). Mangiferin relieved LPS-induced sickness 6 and 24 h after LPS injection; in addition, this compound suppressed LPS-induced IL-6 production after 24 h of LPS induction as well as the downregulation of LPS-induced CBS expression after 6 and 24 h of LPS treatment in the hippocampus. Therefore, mangiferin attenuated sickness behavior by regulating the expression of IL-6 and CBS.

Background Application of dual-energy CT in characterization of adrenal nodules has not been well evaluated. Purpose To evaluate the ability of dual-energy CT scan to differentiate an adrenal adenoma from a metastasis. Material and Methods Fifty-five patients presenting 63 adrenal nodules underwent dual-energy CT scan at tube voltages of 80 kVp and 140 kVp. Mean attenuation values were measured for every nodule at 80/140 kVp and at 40/100 keV. Mean attenuation value changes between 140 kVp and 80 kVp (MAVC140–80kVp) and mean attenuation value changes between 100 keV and 40 keV (MAVC100–40keV) were calculated. Results Of the 63 adrenal nodules available for analyses, 42 nodules were classified as adenoma (26 lipid-rich and 16 lipid-poor) and 21 were classified as metastases. MAVC140–80kVp and MAVC100–40keV of all adenomas (including lipid-poor and lipid-rich) were significantly higher than metastases ( P 140–80kVp and MAVC100–40keV for diagnosing adrenal adenomas were both of 0.964. When the cut-off points were set at 2.42 HU and 6.95 HU for MAVC140–80kVp and MAVC100–40keV, the two parameters both had a sensitivity of 78.6% and a specificity of 100% in adenoma diagnosis. Conclusion Unique energy spectrum information provided by dual-energy CT scan displays a high capacity to distinguish adrenal adenoma from metastasis.

Ginkgolide B (GB) has been shown to exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury. However, the underlying mechanism by which GB prevents ischemic cell death remains unclear. Lysosomal proteases, including cathepsins B and L, have been implicated in ischemic cell death following reperfusion. Therefore, in the present study, we investigated the role of GB with respect to cathepsin-mediated cell death following I/R. Both the expression and enzymatic activity of cathepsins B and L were significantly increased in the ischemic cortex following cerebral I/R injury. We found that GB treatment markedly decreased the activity and expression of cathepsins B and L following I/R. Moreover, GB reduced necrotic and apoptotic cell death following I/R. These data strongly suggest that GB prevents cathepsin-mediated cell death following focal cerebral I/R injury, and they might provide new insights into the mechanism of the neuroprotective effects of GB.

Antibodies directed against contactin-associated protein-like 2 (CASPR2) have been identified in the sera of patients with peripheral and central neurological syndromes, including neuromyotonia, Morvan syndrome (MoS) and autoimmune limbic encephalitis (LE).1 MoS is characterised by peripheral nervous hyperactivity, autonomic dysfunction and LE. Electrocardiac abnormalities, mostly sinus tachycardia, are manifestation of cardiac autonomic dysfunction in patients with MoS.2 Here we describe our observation that electrocardiac abnormalities may present with high prevalence and evolve with the disease courses in CASPR2 antibody (Ab)-positive MoS. We observed severe arrhythmia and cardiac arrest in one patient with CASPR2 Ab-positive MoS and subsequently conducted a retrospective analysis of hospitalised patients with anti-CASPR2 Ab-associated neurological disorders between November 2014 and January 2017 at Peking Union Medical College Hospital. Samples were tested using brain immunohistochemistry and cell-based assays in parallel for the determination of anti-CASPR2 Abs and other antibodies (including anti- N -methyl D-aspartate (NMDA) receptor, LGI1, GABAA receptor and GABAB receptor). Patients were considered to have anti-CASPR2 Abs if both tests were recorded as strongly positive in either of the samples. Written informed consent was obtained from all the patients or their supervisors due to psychiatric and cognitive malfunctions. ### Case 1 A 58-year-old man presented with insomnia and sleepwalking for 2 years. One month before admission to our hospital, he complained of aches all over the body and developed visual and auditory hallucinations, urinary retention, constipation and weight loss (8 kg). The symptoms worsened with episodic anxiety and agitation, accompanied by muscle cramps. On physical …

Background The impairment of the tissue kallikrein (KLK1)–kinin system (KKS) may result in atheroma development. However, it remains unclear if the KKS correlates with coronary artery disease (CAD). Methods KLK1, VEGF and hs-CRP plasma levels were measured in 100 patients newly diagnosed with CAD and 33 CAD-free controls. Patients were followed-up for the incidence of major adverse cardiovascular events (MACE) for 8 months to 2 y. Gene expression of KLK1, CD105 and CD68 was assessed in human coronary endarterectomy specimens. Results Patients with CAD and acute coronary syndrome (ACS) had significantly elevated KLK1 levels. In addition, the concentration of hs-CRP was increased in ACS patients. A strong positive correlation between plasma KLK1 and the severity of CAD was also demonstrated, suggesting that high KLK1 levels are an independent predictor for CAD. MACE during follow-up significantly correlated with KLK1 levels in the ACS group. Unstable coronary plaques demonstrated markedly increased KLK1 levels, macrophage infiltration and high microvessel density. Additionally, KLK1 staining primarily colocalized with macrophages. Conclusions In the present study, plasma KLK1 levels were a useful predictor for the presence and extent of CAD. More extensive studies are, however, necessary in order to validate these findings.

Background : Parafibromin is a protein encoded by the HRPT2 (hyperparathyroidism 2) oncosuppressor gene and its down-regulated expression is involved in pathogenesis of parathyroid, breast, gastric and colorectal carcinomas. This study aimed to clarify the effects of parafibromin expression on the phenotypes and relevant mechanisms of DLD-1 colon carcinoma cells. Methods: DLD-1 cells transfected with a parafibromin-expressing plasmid were subjected to examination of phenotype, including proliferation, differentiation, apoptosis, migration and invasion. Phenotype-related proteins were measured by Western blot. Parafibromin and ki-67 expression was detected by immunohistochemistry on tissue microarrays. Results: The transfectants showed higher proliferation by CCK-8, better differentiation by electron microscopy and ALP activity and more apoptotic resistance to cisplatin by DNA fragmentation than controls. There was no difference in early apoptosis by annexin V, capase-3 activity, migration and invasion between DLD-1 cells and their transfectants. Ectopic parafibromin expression resulted in down-regulated expression of smad4, MEKK, GRP94, GRP78, GSK3β-ser9, and Caspase-9. However, no difference was detectable in caspase-12 and -8 expression. A positive relationship was noted between parafibromin and ki-67 expression in colorectal carcinoma. Conclusions: Parafibromin overexpression could promote cell proliferation, apoptotic resistance, and differentiation of DLD-1 cells. Keywords: Colon carcinoma cells - parafibromin - cell phenotypes - molecular mechanisms

Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation., Hepatitis B infection is a risk factor for hepatocellular carcinoma. Here, the authors characterise viral infection in a cohort of hepatocellular carcinoma patients and find viral integration is more frequent in males than females.

// Yu-Xiao Sun 1 , Chuan-Yu Gao 2 , Yang Lu 3 , Xin Fu 4 , Jun-Ge Jia 1 , Yu-Jie Zhao 1 , Lian-Dong Li 1 , Hong-zhi Dui 1 , Xing-Yu Zhang 1 , Zhi-Ying Li 1 , Lei Lei 1 , Wei-Feng Zhang 1 , Yi-Qiang Yuan 1 1 Department of Cardiology, The Seventh People’s Hospital, Zhengzhou, Henan, 450016, China 2 Department of Cardiology, Henan Provincial People’s Hospital, Zhengzhou, 450000, China 3 Department of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China 4 Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China Correspondence to: Yu-Xiao Sun, email: syxxjb@163.com Yi-Qiang Yuan, email: yiqiangyuan@163.com Keywords: coronary heart disease (CHD), single nucleotide polymorphisms (SNPs), PPAP2B, Chinese Han population, case-control study Received: October 29, 2016 Accepted: December 15, 2016 Published: January 04, 2017 ABSTRACT Little is known about gender-related differences in the association between PPAP2B single nucleotide polymorphisms (SNPs) and coronary heart disease (CHD) in Chinese Han males and females. We therefore conducted a case-control study with 456 cases and 685 healthy controls divided into male and female subgroups. Five PPAP2B polymorphisms (SNPs) were selected and genotyped using Sequenom Mass-ARRAY technology. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression adjusting for age and gender. Allelic model analysis revealed that for PPAP2B rs1759752, allele frequency distributions differed between cases and controls in the male subgroup ( p = 0.015, OR: 1.401, 95%CI: 1.066–1.481). Genetic model analysis revealed that in the male subgroup, rs1759752 was associated with increased CHD risk in the dominant model ( p = 0.035) and overdominant model ( p = 0.045). In the female subgroup, rs12566304 was associated with a decreased CHD risk in the codominant model ( p = 0.038) and overdominant model ( p = 0.031). Additionally, the “GC” haplotypes of rs1759752 and rs1930760 were protective against CHD in males. These observations shed new light on gender-related differences in the association between PPAP2B gene polymorphisms and CHD susceptibility in the Chinese Han population.

Background The effect of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT)-guided dose-painting intensity-modulated radiation therapy (IMRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) is unclear. This study aimed to assess the efficacy and toxicity of such combination. Methods From 2012 to 2014, 213 patients with stage III-IVB NPC received chemoradiotherapy by PET/CT-guided DP-IMRT (group A, n = 101) or CT-based IMRT (group B, n = 112). In group A, subvolume GTVnx-PET (gross tumor volume of nasopharynx in PET images) was defined within GTVnx (gross tumor volume of nasopharynx) as the SUV50%max isocontour; the dose to GTVnx-PET was escalated to DT 75.2 Gy/32 and 77.55 Gy/33 Fx, respectively, for patients with T1-2 and T3-4 disease, respectively. In group B, PGTVnx was irradiated at DT 70.4–72.6 Gy/32–33 Fx in 2.2 Gy per fraction. Results Complete response rates were 99.0% (100/101) and 92.9% (104/112) in groups A and B, respectively (P = 0.037). Compared with CT-based IMRT, FDG-PET/CT guided DP-IMRT significantly improved 3-year local failure-free survival (LFFS, 98.8% vs. 91.3%; P = 0.032), locoregional failure-free survival (LRFFS, 97.2 vs. 91.2%; P = 0.049), distant metastasis-free survival (DMFS, 92.9% vs. 87.4%; P = 0.041), disease free survival (DFS, 87.9% vs. 82.4%; P = 0.02), and overall survival (OS, 91.8% vs. 82.6%; P = 0.049). No statistically significant differences in acute and late toxic effects were observed. Multivariate analysis showed that dose painting (PET/CT-guided DP-IMRT vs CT-based IMRT without DP) was a significant independent prognostic factor for LFFS and DFS. Conclusion FDG-PET/CT guided DP-IMRT plus chemotherapy is associated with a considerable survival benefit, without increasing toxicity in patients with locoregional advanced NPC. Further randomized trials are needed to fully assess the role of PET/CT-guided DP-IMRT.

We aim to explore the potential association between serum gamma-glutamyl transferase levels and functional outcome after aneurysmal subarachnoid hemorrhage in a Chinese population.A total of 386 aneurysmal subarachnoid hemorrhage patients were included in the study from September 2007 to February 2015. Baseline serum gamma-glutamyl transferase levels and 6-month follow-up functional outcomes were determined. A poor outcome was defined as a modified ranking scale score of ⋝ 3. The multivariable logistic model was used to analyze the relationship between serum gamma-glutamyl transferase and clinical outcomes after aneurysmal subarachnoid hemorrhage.The adjusted poor outcome rates of patients with gamma-glutamyl transferase levels of30 U/L, 30-50 U/L and ⋝ 50 U/L were 16.7%, 19.6%, and 34.4%, respectively (P0.01). The age-sex and multivariable adjusted odds ratios (95% confidence intervals) of poor prognosis comparing the top group (⋝ 50 U/L) with the lowest group (30 U/L) were 5.76 (2.74-12.13), 6.64 (2.05-21.52), and 6.36 (1.92-21.02). A significant linear trend existed between gamma-glutamyl transferase level and aneurysmal subarachnoid hemorrhage prognosis. This association was also observed among nondrinkers.Patients with higher gamma-glutamyl transferase levels were more likely to have a poor prognosis. Serum gamma-glutamyl transferase can be considered to be an independent predictor of functional outcomes after aneurysmal subarachnoid hemorrhage.

To explore the effect of Qinghuang Powder (QHP,()combined with Bupi Yishen Decoction (BPYS, ) on myelodysplastic syndromes (MDS) patients with refractory cytopenia with multilineage dysplasia (RCMD) and determine the change of DNA methylation in MDS-RCMD patients after the treatment of Chinese medicine formula.All 308 MDS-RCMD patients were treated with QHP combined with BPYS for 2 months at least, absolute neutrophil count (ANC), hemoglobin (Hb), platelets (PLT), primitive bone marrow cells and chromosome karyotype were chosen as the main evaluation indexes to analyze the treatment effect according to criteria from the MDS International Working Group. Then 43 bone marrow samples from 15 MDS-RCMD patients and 28 healthy donors were obtained for the examination of DNA methylation. Gene Ontology (GO) and Pathway analysis were applied to analyze the methylation data.The overall MDS response rate to QHP was 61.68% (190/360) including hematologic improvement-neutrophil (HI-N) or hematologic improvement-erythroid (HI-E) or hematologic improvement-platelet (HI-P). Patients with anemia had a better response rate than patients with neutropenia or thrombocypenia (55.88% vs 31.54% or 55.88% vs. 36.9%). The DNA methylation microarray analysis disclosed that 4,257 hypermethylated genes were demethylated upon the treatment with QHP and BPYS. GO analysis and Pathway analysis showed that these demethylated genes were involved in a lot of tumor-related pathways and functions.QHP combined with BPYS could effectively treat MDS-RCMD patients through hematologic improvement (HI-N, HI-P or HI-E) and PLT and RBC transfusion independence due to the demethylation, thereby providing another choice for the treatment of patients with MDS-RCMD.

Cardioprotective effects of remote ischaemic conditioning (RIC) in the setting of ischaemic heart disease have been shown recently. But the effects of RIC on heart rate variability (HRV) and cardiac function in patients with stable ischaemic heart failure (IHF) are still unknown.Fifty patients with stable IHF were enrolled and randomly divided into RIC group and control group. Remote ischaemic conditioning treatment was performed twice a day for 6 weeks. A remote is chaemic conditioning protocol consisted of 4×5min inflation/deflation of the blood pressure cuff applied in the upper arm to create intermittent arm ischaemia. B-type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), 24-hour ambulatory electrocardiogram, and 6-minute walk distance (6MWD) were all assessed in two groups.Forty-seven patients completed the study. Remote ischaemic conditioning was well-tolerated by patients in the RIC group after 6 weeks treatment and LVEF showed a significant increase, from 39.2% to 43.4% (p0.001), as well as decreased BNP, increased 6MWD and HRV, but this was not observed in the control group. In addition, the patients treated with RIC also showed improved NYHA class, LVEF, 6MWD, BNP level and HRV compared to control group.This study suggests that a 6-week course of RIC treatment could improve cardiac function and HRV in patients with mild and stable IHF, supporting widespread use of RIC in the daily lives of these patients.

1. Resibufogenin (1), a major bufadienolide of Chinese medicine Chan Su, had a wide range of pharmacological activities. In present work, the metabolism of 1 in male Sprague-Dawley rats was investigated by identifying the metabolites of resibufogenin excreted in rat bile. 2. Following an oral dose of 60 mg/kg resibufagenin, nine metabolites were isolated from bile of rats, and their structures were identified as 3-keto- resibufogenin (2), 3-epi-resibufogenin (3), 5β-hydroxy-3-epi-resibufogenin (4), 1α, 5β-dihydroxy-3-epi-resibufogenin (5), 3α, 5β, 14α, 15β-tetrahydroxyl-bufa- 20, 22-dienolide (6), 3α, 14α, 15β-trihydroxy-bufa-20, 22-dienolide (7), 3-epi- 5β-hydroxy-bufalin (8), 12α, 16β-dihydroxy-3-epi-resibufogenin (9), and 5β, 16β-dihydroxy-3-epi-resibufogenin (10), respectively, on the basis of widely spectroscopic methods including 2D-NMR technology. It is first time to describe the metabolites of 1 in vivo, and metabolites 5-7 and 9-10 are novel. 3. On the basis of these identified metabolites, a possible metabolism pathway for 1 in rats has been proposed. This is the first systematic study on the phase I metabolites of resibufogenin.

The M protein of POEMS syndrome is essentially λ light chain restricted. Several studies have demonstrated the restrict usage of immunoglobulin λ light chain variable region (IGLV) genes in patients with POEMS syndrome. However, these studies only included a limited number of cases, and it is not clear whether the clinical features are influenced by the IGLV gene in POEMS syndrome. Here we demonstrated that the clonal IGLV genes were strictly derived from IGLV 1-40 (11 patients, 36.7 %) and IGLV 1-44 (19, 63.3 %) gene in 30 patients with POEMS syndrome. We further evaluated the relationship between clinical features and IGLV genes. Our study showed that patients with IGLV 1-44 were older than those with IGLV 1-40, and patients with IGLV 1-40 had more severe neuropathy, hypertrichosis, and papilledema. It was suggested that the IGLV gene influenced clinical characteristics in POEMS syndrome.

MicroRNAs (miRNAs) are small, single-stranded, non-protein-coding RNAs of about 22 nucleotides. miRNA molecules have been identified that plays key roles in a broad range of physiologic and pathologic processes. Polymorphisms in the corresponding sequence space are likely to make a significant contribution to phenotypic variation.To assess the variations of rs11614913 T → C in hsa-mir-196a2 and rs3746444 A → G in hsa-mir-499 in the complex etiology of coronary artery disease (CAD), 956 CAD patients diagnosed by coronary arterial angiography and 620 controls were enrolled. Among the patients, 785 (785/956) had complete follow-ups for 42 months. The variant genotypes CC/CT of hsa-mir-196a2 rs11614913 T → C were not associated with a significantly increased risk of CAD (adjusted OR = 1.02, 95% CI = 0.76-1.38), compared with wide genotype TT, but CC and CC/CT genotypes were associated with 34 and 35% increased risks of serious prognosis of CAD (adjusted HR = 1.34, 95% CI = 1.02-1.75 for CC; adjusted HR = 1.35, 95% CI = 1.03-1.75 for CC/CT). In the variant of hsa-mir-499 rs3746444A → G, GG was associated with the 223% increased risk of CAD (adjusted OR = 3.23, 95% CI = 1.56-6.67). Cox regression analysis showed that age, smoking status, numbers of pathological changes in coronary arteries, rs11614913 T → C, and diabetes mellitus were associated with serious prognosis of CAD.Our findings strongly implicate the functional miRNAs polymorphisms of hsa-mir-196a2 and hsa-mir-499 genes may modulate the occurrence or prognosis in Chinese CAD.

POEMS syndrome is a rare clonal plasma cell disorder without standard treatment. Based on the efficacy and low toxicity of a combination of melphalan and dexamethasone (MDex) for light chain amyloidosis, we conducted a prospective study of MDex treatment for patients with newly diagnosed POEMS syndrome. Thirty-one patients (19 men) were enrolled and the median age at the time of diagnosis was 44 years (range, 32-68 years). All patients received 12 cycles of MDex treatment. Twenty-five patients (80.6%) achieved hematologic response including 12 (38.7%) complete remission and 13 (41.9%) partial remission. Of all 31 patients, the neurologic response rate was 100%, assessed by overall neuropathy limitation scale (ONLS). The initial neurologic response was observed in 24 patients (77.4%) at 3 months after treatment and the median time to maximal neurologic response was 12 months (range, 3-15 months). Moreover, MDex substantially improved the level of serum vascular endothelial growth factor and relieved organomegaly, extravascular volume overload, and pulmonary hypertension. Only 6 patients (19.3%) suffered from grade 3 adverse events during treatment. All patients are alive and free of neurologic relapse after the median follow-up time of 21 months. Therefore, MDex is an effective and well-tolerated treatment option for patients with newly diagnosed POEMS syndrome.