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Objective: Antibiotic overuse is one of the major prescription problems in rural China and a major risk factor for antibiotic resistance. Low antibiotic prescription rates can effectively reduce the risk of antibiotic resistance. We hypothesized that under a paperless, computer-based feedback system the rates of antibiotic prescriptions among primary care physicians can be reduced. Methods: A cluster randomized crossover open controlled trial was conducted in 31 hospitals. These hospitals were randomly allocated to two groups to receive the intervention for three months followed by no intervention for three months in a random sequence. The feedback intervention information, which displayed the physicians’ antibiotic prescription rates and ranking, was updated every 10 days. The primary outcome was the 10-day antibiotic prescription rate of the physicians. Results: There were 82 physicians in group 1 (intervention first followed by control) and 81 in group 2 (control first followed by intervention). Baseline comparison showed no significant difference in antibiotic prescription rate between the two groups (30.8% vs 35.2%, P-value = 0.07). At the crossover point, the relative reduction in antibiotic prescription rate was significantly higher among physicians in the intervention group than in the control group (33.1% vs 20.3%, P-value

Abstract Background Acute mountain sickness has become a heavily researched topic in recent years. However, the genetic mechanism and effects have not been elucidated. Our goal is to construct a gene co-expression network to identify the key modules and hub genes associated with high altitude hypoxia. Results The GSE46480 dataset of rapidly transported healthy adults with acute mountain sickness was selected and analyzed by weighted gene co-expression network analysis (WGCNA) to construct a co-expression network. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the data set were carried out using Database for Annotation Visualization and Integrated Discovery (DAVID), and the hub genes were selected. We found that the turquoise module was most significantly correlated with acute mountain sickness. The functional enrichment analysis showed that the turquoise module was related to the apoptotic process, protein transport, and translation processes. The metabolic pathway analysis identified hsa03010:ribosome and hsa04144:endocytosis as the most important pathways in the turquoise module. Ten top 10 hub genes (MRPL3, PSMC6, AIMP1, HAT1, DPY30, ATP5L, COX7B, UQCRB, DPM1, and COMMD6) for acute mountain sickness were identified. Conclusion One module and 10 hub genes were identified, which were related to acute mountain sickness. The reference provided by this module may help to elucidate the mechanism of acute mountain sickness. In addition, the hub genes may be used in the future as a biomarker and therapeutic target for accurate diagnosis and treatment.

The health-maintaining effects of tea on the human body have been widely proven, even with the tea prepared by brewing tea leaves in cold water becoming a new choice other than hot water. In this research, quality and the antioxidant properties of the Pouchong tea infusions prepared with cold water and hot water were determined and explored their relationships under a consumer hedonic test. The results showed that the chemical components of cold tea infusions increased with increasing duration of brewing, and a maximal increment was observed during the first 2 h of brewing. All chemical components under investigation, except caffeine, were found to be higher in the cold tea infusions over 8 h as compared in the hot tea infusions. The antioxidant ability of cold tea infusion increased with increasing duration of brewing and approached the plateau after 12 hours. The chemical components showed a significantly positive correlation with the antioxidant activities (P

BackgroundThe overuse and abuse of antibiotics is a major risk factor for antibiotic resistance in primary care settings of China. In this study, the effectiveness of an automatically-presented, privacy-protecting, computer information technology (IT)-based antibiotic feedback intervention will be evaluated to determine whether it can reduce antibiotic prescribing rates and unreasonable prescribing behaviours.MethodsWe will pilot and develop a cluster-randomised, open controlled, crossover, superiority trial. A total of 320 outpatient physicians in 6 counties of Guizhou province who met the standard will be randomly divided into intervention group and control group with a primary care hospital being the unit of cluster allocation. In the intervention group, the three components of the feedback intervention included: 1. Artificial intelligence (AI)-based real-time warnings of improper antibiotic use; 2. Pop-up windows of antibiotic prescription rate ranking; 3. Distribution of educational manuals. In the control group, no form of intervention will be provided. The trial will last for 6 months and will be divided into two phases of three months each. The two groups will crossover after 3 months. The primary outcome is the 10-day antibiotic prescription rate of physicians. The secondary outcome is the rational use of antibiotic prescriptions. The acceptability and feasibility of this feedback intervention study will be evaluated using both qualitative and quantitative assessment methods.DiscussionThis study will overcome limitations of our previous study, which only focused on reducing antibiotic prescription rates. AI techniques and an educational intervention will be used in this study to effectively reduce antibiotic prescription rates and antibiotic irregularities. This study will also provide new ideas and approaches for further research in this area.Trial registrationISRCTN, ID: ISRCTN13817256. Registered on 11 January 2020.

Background: Workplace social support might have a protective function against migraine in the social context of China, as close co-worker relationships and collectivism are acknowledged as work values in Chinese society. Objectives: This paper aimed to analyse the association between migraine and workplace social support. The validity and reliability of the Chinese version of the Support scale of the Demand-Control-Support Questionnaire (DCSQ) used were also determined. Methods: Following international guidelines, this study was carried out in two stages. Stage I involved translations and pilot testing to assess content and face validity of the Chinese version of the DCSQ Support scale. Stage II was a cross-sectional survey (N = 677 bank employees) to evaluate structural validity, internal consistency and test-retest reliability of the Support scale, as well as to examine the association between workplace social support and a migraine-positive diagnosis. Results: A high level of social support in the workplace was associated with a 74% decreased likelihood of migraine (adjusted OR = 0.26, 95%CI: 0.14–0.46). Of the six aspects of workplace social support, co-worker support had the greatest protective effect (adjusted OR = 0.49, 95% CI: 0.39–0.60). The Chinese version of the DCSQ Support scale established satisfactory content and face validity (I-CVIs ≥ 0.78; S-CVIAVE ≥ 0.90). Confirmatory factor analysis verified its one-dimensional theoretical factor, with adequate internal consistency (Cronbach’s α 0.98; item-total correlations ≥ 0.80) and test-retest reliability (weighted Kappa coefficients 0.81–0.87; percentages agreement 85.23–88.92%). Conclusions: In the Chinese social context, workplace social support could protect against migraine, with the strongest benefit coming from co-workers. This study also provides a Chinese-language DCSQ Support scale as a valid and reliable instrument for measuring workplace social support.

PICALM rs3851179, one of the genes most frequently linked to susceptibility of late-onset Alzheimer’s disease (LOAD), plays a crucial role in regulating amyloid precursor protein, and amyloid β (Aβ) transcytosis. To explore the effects of PICALM and AD continuum stage on cortex thickness, CSF Aβ, and tau, 188 cognitively normal controls, 261 MCI patients, and 140 early LOAD patients were recruited, and each group was divided into rs3851179 A-carriers and GG-carriers. A full factorial ANCOVA was used to analyze the main effects and interactive effects of AD continuum stage, and PICALM. The interactive effects of AD continuum stage and PICALM on cortex thickness and CSF biomarkers were not significant. The main effect of PICALM was significant on the left postcentral cortex thickness, and the cortex thickness of A-carriers was less than that of GG-carriers. The rs3851179 A-carriers displayed higher Aβ42 levels and Aβ42/40 ratios, and lower P/T–tau ratios, compared with GG-carriers. A higher MMSE score was found in A-carriers among the LOAD patients. In conclusion, the main effects of PICALM were independent of AD continuum stage, and PICLAM rs3851179 genotypes may modulate left postcentral cortex thickness, Aβ42 level, and P/T–tau ratio. The rs3851179 A-allele may protect the cognitive function of LOAD patients.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors, characterized by diagnosis at an advanced stage and a poor prognosis. As a member of the S100 protein family, S100A10 regulates multiple biological functions related to cancer progression and metastasis. However, the role of S100A10 in PDAC is still not completely elucidated. In this study, we reported that S100A10 was significantly up-regulated in PDAC tissue and associated with a poor prognosis by integrated bioinformatic analysis and human PDAC tissue samples. In vitro, down-regulation of S100A10 reduced the proliferation, migration, and adhesion of PDAC cell lines, whereas up-regulation of S100A10 showed the opposite effect. Furthermore, LAMB3 was proved to be activated by S100A10 using RNA-sequencing and western blotting. The effect of LAMB3 on the proliferation, migration, and adhesion of PDAC cells was similar to that of S100A10. Up-regulation or down-regulation of LAMB3 could reverse the corresponding effect of S100A10. Moreover, we validated S100A10 activates LAMB3 through the JNK pathway, and LAMB3 was further proved to interact with LAMC2. Mice-bearing orthotopic pancreatic tumors showed that S100A10 knocked-down PANC-1 cells had a smaller tumor size than the control group. In conclusion, S100A10 promotes PDAC cells proliferation, migration, and adhesion through JNK/LAMB3-LAMC2 axis.

One of the main challenges in co-injection molding is how to predict the skin to core morphology accurately and then manage it properly, especially after skin material has been broken through. In this study, the formation of the Core-Skin-Core (CSC) structure and its physical mechanism in a two-stage co-injection molding has been studied based on the ASTM D638 TYPE V system by using both numerical simulation and experimental observation. Results showed that when the skin to core ratio is selected properly (say 30/70), the CSC structure can be observed clearly at central location for 30SFPP/30SFPP system. When the skin to core ratio and operation conditions are fixed, regardless of material arrangement (including 30SFPP/30SFPP; PP/PP; 30SFPP/PP; and PP/30SFPP systems), the morphologies of the CSC structures are very close for all systems. This CSC structure can be further validated by using μ-CT scan and image analysis technologies perfectly. Furthermore, the influences of various operation parameters on the CSC structure variation have been investigated. Results exhibited that the CSC structure does not change significantly irrespective of the flow rate changing, melt temperature varying, or even mold temperature being modified. Moreover, the mechanism to generate the CSC structure can be derived using the melt front movement of the numerical simulation. It is worth noting that after the skin material was broken through, the core material travelled ahead with fountain flow to occupy the flow front. In the same period, the proper amount of skin material with certain inertia of enough kinetic energy will keep going to penetrate the new coming core material to travel until the end of filling. It ends up with this special CSC structure.

The experiment aimed to assess the effects of sucrose-chelated trace elements as substitutes for inorganic trace elements on the growth performance, carcass traits, meat quality, and muscle trace element deposition in growingfinishing pigs. Eighty-four castrated boars (70±3) kg were randomly divided into two treatment groups, each treatment with six replicates, and each replicate consisting of seven pigs. The control group (IE group) was fed a diet supplemented with 1% inorganic trace elements, and the experimental group (SE group) was fed a diet supplemented with 1% sucrosechelated trace elements. The experiment lasted for 56 days. The results showed that compared to IE group, the average daily gain, final weight, carcass weight, and backfat thickness of growing-finishing pigs in SE group increased ( P<0.05), the drip loss and refrigeration loss of the longissimus dorsi muscle decreased ( P<0.05), and the thawing loss showed a trend of reduction ( P>0.05). The redness (a*) value of the longissimus dorsi muscle of SE group increased after 45 minutes and one day of storage ( P<0.05). The T-AOC, T-SOD, and GSH-Px activities of the longissimus dorsi muscle of SE group were enhanced ( P<0.05), and the MDA content decreased ( P<0.05). Compared to IE group, the Cu and Se content in the longissimus dorsi muscle in SE group increased ( P<0.05), and the Fe and Mn content in the hind leg muscle increased ( P<0.05).The study indicates that using sucrose-chelated trace elements in the diet as substitutes for inorganic trace elements can improve the growth performance, carcass traits, meat quality, and muscle antioxidant status of growing-finishing pigs, and promote the deposition of trace elements in muscles. [ABSTRACT FROM AUTHOR]

We conduct a systematic search for quasars with periodic variations from the archival photometric data of the Zwicky Transient Facility by cross-matching with the quasar catalogues of the Sloan Digital Sky Survey and Véron-Cetty and Véron. We first select out 184 primitive periodic candidates using the generalized Lomb–Scargle periodogram and autocorrelation function and then estimate their statistical significance of periodicity based on two red-noise models, i.e. damped random walk (DRW) and single power-law (SPL) models. As such, we finally identify 106 (DRW) and 86 (SPL) candidates with the most significant periodic variations out of 143 700 quasars. We further compare DRW and SPL models using Bayes factors, which indicate a relative preference of the SPL model for our primitive sample. We thus adopt the candidates identified with SPL as the final sample and summarize its basic properties. We extend the light curves of the selected candidates by supplying other archival survey data to verify their periodicity. However, only three candidates (with 6–8 cycles of periods) meet the selection criteria. This result clearly implies that, instead of being strictly periodic, the variability must be quasi-periodic or caused by stochastic red-noise. This exerts a challenge to the existing search approaches and calls for developing new effective methods. [ABSTRACT FROM AUTHOR]

Objective To explore the change of serum sex hormones and 25-hydroxycholecalciferol [25-(OH)-D3 ] level in postmenopausal female patients with benign paroxysmal positional vertigo (BPPV). Methods Electrochemiluminescence (ECL) assay was employed to detect the serum levels of estradiol (E2), progesterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), and 25-(OH)-D3 in 63 female postmenopausal BPPV patients with age 50-80 years from September 1, 2015 to February 1, 2017. Spearman rank correlation analysis was used to analyze the relation between age and E2 , E2 and 25-(OH)-D3. Univariate and multivariate stepwise Logistic regression analysis were used to screen the risk factors for BPPV. Results The serum levels of E2 [15.67 (10.96, 22.15) pg/ml] and 25-(OH)-D3 [(24.24 ± 1.05) ng/ml] in BPPV group were lower than those in control group [E2: 31.78 (25.60, 39.50) pg/ml, 25-(OH)-D3: (27.62 ± 0.76) ng/ml], and the differences were statistically significant (Z = -6.768, P = 0.000; t = -2.605, P = 0.010). There was no significant difference on progesterone, LH and FSH between 2 groups. Correlation analysis showed there was no relation between E2 and 25-(OH)-D3 levels in both groups. There was a negative correlation between age and E2 in control group (rs = -0.263, P = 0.038), but no correlation in BPPV group. Multivariate Logistic regression analysis showed decreased serum E2 and 25-(OH)-D3 levels maybe the risk factors for postmenopausal female BPPV patients. Conclusions E2 and 25-(OH)-D3 deficiency are independent risk factors for BPPV in postmenopausal female patients. DOI: 10.3969/j.issn.1672-6731.2019.01.007

As the large amount of video surveillance data floods into cloud data center, achieving load balancing in a cloud network has become a challenging problem. Meanwhile, we hope the cloud data center maintains low latency, low consumption, and high throughput performance when transmitting massive amounts of data. OpenFlow enables a software-defined solution through programing to control the scheduling of data flow in the cloud data center. However, the existing scheduling algorithm of the data center cannot cope with the congestion of the network center effectively. Even for some dynamic scheduling algorithms, adjustments can only be made after congestion occurs. Hence, we propose a proactive and dynamically adjusted mixed-flow load-balanced scheduling (MFLBS) algorithm, which not only takes into account the different sizes of flows in the network but also maintains maximum throughput while balancing the load. In this paper, the MFLBS problem was formulated, along with a set of heuristic algorithms for real-time feedback and adjustment. Experiments with mesh and tree network models show that our MFLBS is significantly better than other dynamic scheduling algorithms, including one-hop DLBS and static scheduling algorithm FCFS. The MFLBS algorithm can effectively reduce the delay of small flows and average delay while maintaining high throughput.

Abstract Background Transcription factor forkhead box M1 (FOXM1) is a crucial regulator in colorectal cancer (CRC) progression. However, the regulatory mechanisms causing dysregulation of FOXM1 in CRC remain unclear. Methods Dual-luciferase reporter assay was conducted to determine FOXM1 as miR-6868-5p target. The function of miR-6868-5p and FOXM1 in CRC angiogenesis was verified in vitro. Intratumoral injection model was constructed to explore the effect of miR-6868-5p on angiogenesis in vivo. Chromatin immunoprecipitation assays were used to assess direct binding of H3K27me3 to the miR-6868 promoter. Results Through integrated analysis, we identified miR-6868-5p as the potent regulator of FOXM1. Overexpression of miR-6868-5p in CRC cells inhibited the angiogenic properties of co-cultured endothelial cells, whereas silencing of miR-6868-5p had opposite effects. In vivo delivery of miR-6868-5p blocked tumor angiogenesis in nude mice, resulting in tumor growth inhibition. Rescue of FOXM1 reversed the effect of miR-6868-5p on tumor angiogenesis. Further mechanistic study revealed that FOXM1 promoted the production of IL-8, which was responsible for the miR-6868-5p/FOXM1 axis-regulated angiogenesis. Reciprocally, FOXM1 inhibited miR-6868-5p expression through EZH2-mediated H3K27me3 on miR-6868-5p promoter, thus forming a feedback circuit. Clinically, the level of miR-6868-5p was downregulated in CRC tissues and inversely correlated with microvessel density as well as levels of FOXM1 and IL-8 in tumor specimens. Conclusions Together, these data identify miR-6868-5p as a novel determinant of FOXM1 expression and establish a miR-6868-5p/FOXM1 regulatory circuit for CRC angiogenesis, providing potential target for CRC treatment.

Background: Intestinal microbiota is a novel drug target of metabolic diseases, especially for those with poor oral bioavailability. Nuciferine, with poor bioavailability, has an anti-hyperlipidemic effect at low dosages. Purpose: In the present study, we aimed to explore the role of intestinal microbiota in the anti-hyperlipidemic function of nuciferine and identify the key bacterial targets that might confer the therapeutic actions. Methods: The contribution of gut microbes in the anti-hyperlipidemic effect of nuciferine was evaluated by conventional and antibiotic-established pseudo-sterile mice. Whole-metagenome shotgun sequencing was used to characterize the changes in microbial communities by various agents. Results: Nuciferine exhibited potent anti-hyperlipidemic and liver steatosis-alleviating effects at the doses of 7.5-30 mg/kg. The beneficial effects of nuciferine were substantially abolished when combined with antibiotics. Metagenomic analysis showed that nuciferine significantly shifted the microbial structure, and the enrichment of Akkermansia muciniphila was closely related to the therapeutic effect of nuciferine. Conclusions: Our results revealed that gut microbiota played an essential role in the anti-hyperlipidemic effect of nuciferine, and enrichment of Akkermansia muciniphila represented a key mechanism through which nuciferine exerted its therapeutic effects.

Background. Endometrial carcinoma (EC) is one of the major gynecologic malignancy cancers affecting females with dismal prognosis and high mortality around the world. Numerous studies have proven that an aberrant level of long noncoding RNAs is present in many endometrial cancer patients, while the underlying molecular mechanism remains unclear. Method. The expression levels of lncRNA OIP5-AS1, miR200c-3p, and PTEN were measured by a quantitative real-time polymerase chain reaction in endometrial cancer tissue and endometrial cancer cells. CCK8 assay, wound-healing assay, and cell colony formation were applied to evaluate cell proliferation, cell migration, and cell colony formation ability. Cell cycle and cell apoptosis were detected by flow cytometry. The interactions between OIP5-AS1, miR200c-3p, and PTEN were explored by luciferase activity. Results. In the present study, we demonstrated that long noncoding RNA OIP5-AS1 was significantly reduced in EC tissue compared with normal tissue. The lower expression level of OIP5-AS1 was also confirmed in four kinds of EC cell lines compared with the normal endometrial cell line. Gain- and loss-of-function of experiments indicated that upregulation of OIP5-AS1 could inhibit the proliferation, migration, and invasion of EC cells in vitro. Meanwhile, overexpression of OIP5-AS1 could also suppress the growth of tumor in the xenograft model. Moreover, further study revealed that miR-200c-3p could bind to OIP5-AS1, and the loss function of miR-200c-3p could reverse the elevated OIP5-AS1’s inhibitory effect on the progression of EC. Furthermore, we found that downregulation of miR-200c-3p was inversely correlated with PTEN expression in EC cells. Reduced OIP5-AS1 could lead to the accumulation of miR-200c-3p, which could induce the upregulation of PTEN indirectly. Conclusion. Our study demonstrated a novel molecular mechanism that lncRNA OIP5-AS1 could modulate the progression of EC by combining competitively with miR-200c-3p to control the PTEN/AKT pathway in EC cells, which might supply important information for developing novel therapeutic strategies for EC patients.

Summary: The Indo-Pacific humpback dolphin (Sousa chinensis) is a small inshore species of odontocete cetacean listed as Vulnerable on the IUCN Red List. Here, we report on the evolution of S. chinensis chromosomes from its cetruminant ancestor and elucidate the evolutionary history and population genetics of two neighboring S. chinensis populations. We found that breakpoints in ancestral chromosomes leading to S. chinensis could have affected the function of genes related to kidney filtration, body development, and immunity. Resequencing of individuals from two neighboring populations in the northwestern South China Sea, Leizhou Bay and Sanniang Bay, revealed genetic differentiation, low diversity, and small contemporary effective population sizes. Demographic analyses showed a marked decrease in the population size of the two investigated populations over the last ~4,000 years, possibly related to climatic oscillations. This study implies a high risk of extinction and strong conservation requirement for the Indo-Pacific humpback dolphin.

Purposes: To measure expression levels of CD47 during endometrial carcinoma development, and to determine specific modulatory effects.Methods: CD47 expression levels in endometrial carcinoma tissues and adjacent tissues were analyzed using qRT-PCR. CD47-overexpressed or downregulated cell models were established using CD47 plasmid or CD47 shRNA. The effects of CD47 on HEC-1A and Ishikawa cell growth were evaluated using CCK-8 assays. Migration ability of transfected HEC-1A and Ishikawa cells were examined using wound healing assays. Flow cytometry was used to measure the effects of CD47 on apoptosis and the cell cycle in HEC-1A and Ishikawa cells. Western blot was used to analyze the correlation between CD47 expression level and PI3K/Akt/mTOR signaling pathway.Results: Highly expressed CD47 was observed in endometrial carcinoma tissues, with higher levels in more advanced tissues than in early tissues. Upregulation of CD47 enhanced cell viability and migration ability in HEC-1A and Ishikawa cells, while silencing CD47 caused the opposite results. CD47 overexpression suppressed apoptosis and inhibited cell cycle arrest in HEC-1A and Ishikawa cells. CD47 upregulation contributes to the activation of PI3K/Akt/mTOR signaling pathway in endometrial carcinoma cells.Conclusion: CD47 exerts oncogenic functions in endometrial carcinoma by activating PI3K/Akt/mTOR signaling, suggesting it may be a novel immunotherapeutic target for therapeutic interventions.

Objective: This study aimed to investigate the potential value of circumferential resection margin (CRM) in colon cancer prognostics.Summary Background Data: CRM has been extensively studied as an important prognostic factor in rectal and esophageal cancer, but not in colon cancer.Methods: Data from 6,681 CRM-positive patients and 25,908 CRM-negative patients diagnosed with colon cancer in 2010–2015 were obtained from the Surveillance, Epidemiology, and End Results database. Statistical analysis methods utilized included the chi-square test, Kaplan-Meier estimates, Cox proportional, and X-tile software analyses.Results: After propensity score matching, CRM positivity was found to be negatively related with survival (P < 0.001). X-tile software identified 0 and 30 mm as optimal cutoff values (P < 0.001) for prognosis, which was applicable only in stage II–IV patients. A 20 and 33% risk decrease were observed in patients with CRM between 0 and 30 mm [95% confidence interval (CI) = 0.76–0.84], and larger than 30 mm (95% CI = 0.62–0.71), respectively. Chemotherapy strongly benefited prognosis with a hazard ratio of 0.36 (95% CI = 0.34–0.38) for overall survival (OS). Patients with a CRM value of 0–30 mm seemed to benefit most from chemotherapy compared with other groups. CRM and number of regional lymph nodes are independent risk factors, and the latter is a good substitute for CRM in AJCC stage I patients.Conclusion: CRM positivity is a strong unfavorable survival indicator for colon cancer patients. A better outcome is expected with CRM values larger than 30 mm. This cutoff value only applied to stage II–IV patients. For stage I patients, number of regional lymph nodes is a good substitute to predict survival. Chemotherapy was another favorable prognostic factor, especially for patients with a CRM value between 0 and 30 mm.

Background: Whether statins can reduce the incidence of cancers has been an interesting topic in recent years. This meta-analysis aimed to determine the relationship between statin treatment with the risk of hepatocellular carcinoma. Methods: Studies published up to July 2019 were screened from databases. The data from approved studies were pooled. Random-effects or fixed-effects model was used to calculate the relative risk with 95% CIs in the overall group and subgroups. Sensitivity and meta-regression analyses were performed, and publication bias was evaluated. Results: A total of 18 studies involving 1 611 596 patients were included in this meta-analysis. The overall result showed a significantly reduced risk of hepatocellular carcinoma (relative risk = 0.54, 95% CI: 0.42-0.66) in statin users. In comparison to the risk in nonstatin users, the risk of hepatocellular carcinoma was reduced in all subgroups. The dose of statins and their pharmacokinetics can partly explain the heterogeneity in the overall meta-analysis ( I 2 = 94.6%, P = .000). A dose-dependent effect of statin use for the reduced risk of hepatocellular carcinoma was found. Conclusions: Findings from this meta-analysis support that statin use can significantly reduce the incidence of hepatocellular carcinoma.

Acute phase reactants (APRs) are secretory proteins exhibiting large expression changes in response to proinflammatory cytokines. Here we show that the expression pattern of a major human APR, that is C-reactive protein (CRP), is casually determined by DNMT3A and TET2-tuned promoter methylation status. CRP features a CpG-poor promoter with its CpG motifs located in binding sites of STAT3, C/EBP-β and NF-κB. These motifs are highly methylated at the resting state, but undergo STAT3- and NF-κB-dependent demethylation upon cytokine stimulation, leading to markedly enhanced recruitment of C/EBP-β that boosts CRP expression. Withdrawal of cytokines, by contrast, results in a rapid recovery of promoter methylation and termination of CRP induction. Further analysis suggests that reversible methylation also regulates the expression of highly inducible genes carrying CpG-poor promoters with APRs as representatives. Therefore, these CpG-poor promoters may evolve CpG-containing TF binding sites to harness dynamic methylation for prompt and reversible responses.

Abstract Background Metabolic syndrome (MetS) has been established as a risk for cardiovascular diseases and mortality in hemodialysis patients. Energy intake (EI) is an important nutritional therapy for preventing MetS. We examined the association of self-reported dietary EI with metabolic abnormalities and MetS among hemodialysis patients. Methods A cross-sectional study design was carried out from September 2013 to April 2017 in seven hemodialysis centers. Data were collected from 228 hemodialysis patients with acceptable EI report, 20 years old and above, underwent three hemodialysis sessions a week for at least past 3 months. Dietary EI was evaluated by a three-day dietary record, and confirmed by 24-h dietary recall. Body compositions were measured by bioelectrical impedance analysis. Biochemical data were analyzed using standard laboratory tests. The cut-off values of daily EI were 30 kcal/kg, and 35 kcal/kg for age ≥ 60 years and

Oxygen deficiency in the plateau environment weakens aerobic metabolism and reduces the energy supply, leading to high-altitude diseases including decreased circulatory function, decreased nutrient and energy supply to tissues and organs, and decreased waste discharge. The involvement of many metabolic pathways is reflected in dramatic changes in levels of endogenous small molecule metabolites. Metabolomics represents a promising technique for mechanistic studies and drug screening, and metabonomics, or quantitative metabolomics, has been increasingly applied to the study of hypoxic diseases and their pathogenesis, as well as to pharmacodynamics at high altitudes. In this article, we review the recent literature on the pathogenesis of altitude hypoxia and the clinical and preclinical metabonomics of drug interventions. Endogenous metabolites and metabolic pathways change significantly under high-altitude hypoxia. Some drug interventions have also been shown to regulate pathway metabolism, and the problems of applying metabonomics to hypoxic diseases at high altitude and the prospects for its future application are summarized.

Hyperhomocysteinemia has been shown to be associated with neurodegenerative diseases; however, lesions or histological changes and mechanisms underlying homocysteine-induced injury in olfactory bulb neurons remain unclear. In this study, hyperhomocysteinemia was induced in apolipoprotein E-deficient mice with 1.7% methionine. Pathological changes in the olfactory bulb were observed through hematoxylin-eosin and Pischingert staining. Cell apoptosis in the olfactory bulb was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Transmission electron microscopy revealed an abnormal ultrastructure of neurons. Furthermore, immunoreactivity and expression of the hairy enhancer of the split 1 (Hes1) and Hes5 were measured using immunohistochemistry, immunofluorescence, and western blot assay. Our results revealed no significant structural abnormality in the olfactory bulb of hyperhomocysteinemic mice. However, the number of TUNEL-positive cells increased in the olfactory bulb, lipofuscin and vacuolization were visible in mitochondria, and the expression of Hes1 and Hes5 decreased. These findings confirm that hyperhomocysteinemia induces injury in olfactory bulb neurons by downregulating Hes1 and Hes5 expression.

Background: Fibroblasts were the main seed cells in the studies of tissue engineering of the pelvic floor ligament. Basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) were widely studied but at various concentrations. This study aimed to optimize the concentrations of combined bFGF and EGF by evaluating their effects on proliferation and collagen secretion of fibroblasts. Methods: Fibroblasts were differentiated from rat adipose mesenchymal stem cells (ADSCs). Flow cytometry and immunohistochemistry were used for cell identification. The growth factors were applied at concentrations of 0, 1, 10, and 100 ng/ml as three groups: (1) bFGF alone, (2) EGF alone, and (3) bFGF mixed with EGF. Cell proliferation was evaluated by Cell Counting Kit-8 assays. Expression of Type I and III collagen (Col-I and Col-III) mRNAs was evaluated by real-time quantitative reverse transcription-polymerase chain reaction. Statistical analysis was performed with SPSS software and GraphPad Prism using one-way analysis of variance and multiple t-test. Results: ADSCs were successfully isolated from rat adipose tissue as identified by expression of typical surface markers CD29, CD44, CD90, and CD45 in flow cytometry. Fibroblasts induced from ADSC, compared with ADSCs, were with higher mRNA expression levels of Col I and Col III (F = 1.29, P = 0.0390). bFGF, EGF, and the mixture of bFGF with EGF can enhanced fibroblasts proliferation, and the concentration of 10 ng/ml of the mixture of bFGF with EGF displayed most effectively (all P < 0.05). The expression levels of Col-I and Col-III mRNAs in fibroblasts displayed significant increases in the 10 ng/ml bFGF combined with EGF group (all P < 0.05). Conclusions: The optimal concentration of both bFGF and EGF to promote cell proliferation and collagen expression in fibroblasts was 10 ng/ml at which fibroblasts grew faster and secreted more Type I and III collagens into the extracellular matrix, which might contribute to the stability of the pelvic floor microenvironment.

Purpose: Wafer bonding is a key process for 3 D advanced packaging of integrated circuits. It requires very high accuracy for the wafer alignment. To solve the problems of large movement stroke, position calibration error and low production efficiency in optical alignment, this paper aims to propose a new wafer magnetic alignment technology (MAT) which is based on tunnel magneto resistance effect. MAT can realize micro distance alignment and reduces the design and manufacturing difficulty of wafer bonding equipment. Design/methodology/approach: The current methods and existing problems of wafer optical alignment are introduced, and the mechanism and realization process of wafer magnetic alignment are proposed. Micro magnetic column (MMC) marks are designed on the wafer by the semiconductor manufacturing process. The mathematical model of the space magnetic field of the MMC is established, and the magnetic field distribution of the MMC alignment is numerically simulated and visualized. The relationship between the alignment accuracy and the MMC diameter, MMC remanence, MMC thickness and sensor measurement height was studied. Findings: The simulation analysis shows that the overlapping double MMCs can align the wafer with accuracy within 1 µm and can control the bonding distance within the micrometer range to improve the alignment efficiency. Originality/value: Magnetic alignment technology provides a new idea for wafer bonding alignment, which is expected to improve the accuracy and efficiency of wafer bonding. [ABSTRACT FROM AUTHOR]

The harmless treatment and resource utilization of the high boiling chlorosilane produced by products in the process of polycrystalline silicon production can be realized by using organic amine catalyst. The effects of reaction temperature and catalyst type on the catalytic cracking of high-boiling chlorosilane was investigated and the reaction mechanism was analyzed. The results showed that, using N,N-dimethylbenzylamine as the catalyst, at a reaction temperature of 130 ~ 135 °C, a reaction time of 1.5 h, and a catalyst amount of 8%, the yield of monosilane product could reach 79.99%. [ABSTRACT FROM AUTHOR]