Survival benefit of postoperative radioiodine therapy among patients with intermediate-risk differentiated thyroid carcinoma.

BACKGROUND: The 2015 American Thyroid Association (ATA) guidelines proposed the use of the ATA Risk Stratification System and American Joint Committee on Cancer Tumor-Node-Metastasis (AJCC/TNM) Staging System for postoperative radioiodine decision-making. However, the management of patients with intermediate-risk differentiated thyroid carcinoma (DTC) is not well defined. In this study, we aimed to evaluate the therapeutic efficacy of radioactive iodine therapy (RAIT) among various subgroups of patients with intermediate-risk DTC after surgery. METHODS: This was a retrospective study based on the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). The DTC patients with intermediate risk of recurrence were divided into two groups (treated or not treated with radioactive iodine (RAI)). As the treatment was not randomly assigned, stabilized inverse probability treatment weighting (sIPTW) was used to reduce selection bias. We used the Kaplan-Meier method and log-rank test to analyze overall survival (OS) and cancer-specific survival (CSS). RESULTS: Kaplan-Meier analysis after sIPTW found a significant difference in OS and CSS between no RAIT and RAIT (log-rank test, P < 0.0001; P = 0.0019, respectively). The Kaplan-Meier curves of CSS in age cutoff of 55 years showed a significant association between no RAIT and RAIT (log-rank test, P = 0.0045). Univariate and multivariate Cox regression showed RAIT was associated with a reduced risk of mortality compared with no RAIT (hazard ratio [HR] 0.59, 95% confidence interval [95% CI 0.44-0.80]). Age (≥ 55) years showed a worse CSS regardless of whether or not a patient was treated or not treated with RAI ([HR] 8.91, 95% confidence interval [95% CI 6.19-12.84]). CONCLUSIONS: RAIT improves OS and CSS in patients with intermediate-risk DTC after surgery. 55 years is a more appropriate prognostic age cutoff for the relevant classification systems and is a crucial consideration in RAI decision-making. Therefore, we need individualized treatment plans.

Socioeconomic disparities and regional environment are associated with cervical lymph node metastases in children and adolescents with differentiated thyroid cancer: developing a web-based predictive model.

Purpose: To establish an online predictive model for the prediction of cervical lymph node metastasis (CLNM) in children and adolescents with differentiated thyroid cancer (caDTC). And analyze the impact between socioeconomic disparities, regional environment and CLNM. Methods: We retrospectively analyzed clinicopathological and sociodemographic data of caDTC from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019. Risk factors for CLNM in caDTC were analyzed using univariate and multivariate logistic regression (LR). And use the extreme gradient boosting (XGBoost) algorithm and other commonly used ML algorithms to build CLNM prediction models. Model performance assessment and visualization were performed using the area under the receiver operating characteristic (AUROC) curve and SHapley Additive exPlanations (SHAP). Results: In addition to common risk factors, our study found that median household income and living regional were strongly associated with CLNM. Whether in the training set or the validation set, among the ML models constructed based on these variables, the XGBoost model has the best predictive performance. After 10-fold cross-validation, the prediction performance of the model can reach the best, and its best AUROC value is 0.766 (95%CI: 0.745-0.786) in the training set, 0.736 (95%CI: 0.670-0.802) in the validation set, and 0.733 (95%CI: 0.683-0.783) in the test set. Based on this XGBoost model combined with SHAP method, we constructed a web-base predictive system. Conclusion: The online prediction model based on the XGBoost algorithm can dynamically estimate the risk probability of CLNM in caDTC, so as to provide patients with personalized treatment advice.

Integrated application of transcriptomics and metabolomics provides insight into the mechanism of Eimeria tenella resistance to maduramycin.

Avian coccidiosis, caused by Eimeria parasites, continues to devastate the poultry industry and results in significant economic losses. Ionophore coccidiostats, such as maduramycin and monensin, are widely used for prophylaxis of coccidiosis in poultry. Nevertheless, their efficacy has been challenged by widespread drug resistance. However, the underlying mechanisms have not been revealed. Understanding the targets and resistance mechanisms to anticoccidials is critical to combat this major parasitic disease. In the present study, maduramycin-resistant (MRR) and drug-sensitive (DS) sporozoites of Eimeria tenella were purified for transcriptomic and metabolomic analysis. The transcriptome analysis revealed 5016 differentially expressed genes (DEGs) in MRR compared to DS, and KEGG pathway enrichment analysis indicated that DEGs were involved in spliceosome, carbon metabolism, glycolysis, and biosynthesis of amino acids. In the untargeted metabolomics assay, 297 differentially expressed metabolites (DEMs) were identified in MRR compared to DS, and KEGG pathway enrichment analysis indicated that these DEMs were involved in 10 pathways, including fructose and mannose metabolism, cysteine and methionine metabolism, arginine and proline metabolism, and glutathione metabolism. Targeted metabolomic analysis revealed 14 DEMs in MRR compared to DS, and KEGG pathway analysis indicated that these DEMs were involved in 20 pathways, including fructose and mannose metabolism, glycolysis/gluconeogenesis, and carbon metabolism. Compared to DS, energy homeostasis and amino acid metabolism were differentially regulated in MRR. Our results provide gene and metabolite expression landscapes of E. tenella following maduramycin induction. This study is the first work involving integrated transcriptomic and metabolomic analyses to identify the key pathways to understand the molecular and metabolic mechanisms underlying drug resistance to polyether ionophores in coccidia.

Association Between Dietary Antioxidant Quality Score (DAQS) and All-Cause Mortality in Hypertensive Adults: A Retrospective Cohort Study from the NHANES Database.

This study aimed to explore the association between the dietary antioxidant quality scores (DAQS) and all-cause mortality in hypertensive adults. In this retrospective cohort study, participants aged ≥ 18 years with hypertension were extracted from the National Health and Nutrition Examination Survey (NAHNES) 2007-2018. Outcome was all-cause mortality of hypertensive participants. DAQS was the exposure variable calculated based on the intake of vitamin A, C, E, zinc, selenium, and magnesium. The weighted univariable and multivariable COX proportional hazards regression models were utilized to explore the association between the DAQS and the all-cause mortality in hypertensive patients and were described as hazard ratios (HRs) and 95% confidence intervals (CIs). Subgroup analyses based on different age, gender, diabetes, and cardiovascular disease (CVD) history were further assessed this association. A total of 16,240 participants were finally included in this study. Until 12 December 2019, 2710 (16.69%) all-cause deaths were documented. After adjustment for confounding variables, high DAQS was associated with the lower all-cause mortality (HR = 0.83, 95%CI: 0.72-0.96) in hypertensive patients. Subgroup analyses suggested that the association between DAQS and the all-cause mortality in hypertensive patients remain robust, especially in patients with female (HR = 0.77, 95%CI: 0.63-0.95), aged ≥ 60 years (HR = 0.81, 95%CI: 0.69-0.96). High DAQS was associated with the lower odds of all-cause mortality in adults with hypertension and are a promising intervention to be further explored in hypertensive patients.

Knockout and Double Knockout of Cathepsin K and Mmp9 reveals a novel function of Cathepsin K as a regulator of osteoclast gene expression and bone homeostasis.

Cathepsins play a role in regulation of cell function through their presence in the cell nucleus. However, the role of Cathepsin K (Ctsk) as an epigenetic regulator in osteoclasts remains unknown. Our data demonstrated that Ctsk-/-Mmp9-/- mice have a striking phenotype with a 5-fold increase in bone volume compared with WT. RNA-seq analysis of Ctsk-/- , Mmp9-/- and Ctsk-/-/Mmp9-/- osteoclasts revealed their distinct functions in gene expression regulation, including reduced Cebpa expression, increased Nfatc1 expression, and in signaling pathways activity regulation. Western blots and qPCR data validated these changes. ATAC-seq profiling of Ctsk-/- , Mmp9-/-, and Ctsk-/-/Mmp9-/- osteoclasts indicated the changes resulted from reduced chromatin openness in the promoter region of Cebpa and increased chromatin openness in Nfatc1 promoter in Ctsk-/-/Mmp9-/- osteoclasts compared to that in osteoclasts of WT, Ctsk/- and Mmp9-/- . We found co-localization of Ctsk with c-Fos and cleavage of H3K27me3 in wild-type osteoclasts. Remarkably, cleavage of H3K27me3 was blocked in osteoclasts of Ctsk-/- and Ctsk-/-/Mmp9-/- mice, suggesting that Ctsk may epigenetically regulate distinctive groups of genes' expression by regulating proteolysis of H3K27me3. Ctsk-/-/Mmp9-/- double knockout dramatically protects against ovariectomy induced bone loss. We found that Ctsk may function as an essential epigenetic regulator in modulating levels of H3K27me3 in osteoclast activation and maintaining bone homeostasis. Our study revealed complementary and unique functions of Ctsk as epigenetic regulators for maintaining osteoclast activation and bone homeostasis by orchestrating multiple signaling pathways and targeting both Ctsk and Mmp9 is a novel therapeutic approach for osteolytic diseases such as osteoporosis.

Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate osteoarthritis of the knee in mice model by interacting with METTL3 to reduce m6A of NLRP3 in macrophage.

BACKGROUND: Osteoarthritis (OA) is a prevalent degenerative joint disease that not only significantly impairs the quality of life of middle-aged and elderly individuals but also imposes a significant financial burden on patients and society. Due to their significant biological properties, extracellular vesicles (EVs) have steadily received great attention in OA treatment. This study aimed to investigate the influence of EVs on chondrocyte proliferation, migration, and apoptosis and their protective efficacy against OA in mice. METHODS: The protective impact of EVs derived from human umbilical cord mesenchymal stem cells (hucMSCs-EVs) on OA in mice was investigated by establishing a mouse OA model by surgically destabilizing the medial meniscus (DMM). Human chondrocytes were isolated from the cartilage of patients undergoing total knee arthroplasty (TKA) and cultured with THP-1 cells to mimic the in vivo inflammatory environment. Levels of inflammatory factors were then determined in different groups, and the impacts of EVs on chondrocyte proliferation, migration, apoptosis, and cartilage extracellular matrix (ECM) metabolism were explored. N6-methyladenosine (m6A) level of mRNA and methyltransferase-like 3 (METTL3) protein expression in the cells was also measured in addition to microRNA analysis to elucidate the molecular mechanism of exosomal therapy. RESULTS: The results indicated that hucMSCs-EVs slowed OA progression, decreased osteophyte production, increased COL2A1 and Aggrecan expression, and inhibited ADAMTS5 and MMP13 overexpression in the knee joint of mice via decreasing pro-inflammatory factor secretion. The in vitro cell line analysis revealed that EVs enhanced chondrocyte proliferation and migration while inhibiting apoptosis. METTL3 is responsible for these protective effects. Further investigations revealed that EVs decreased the m6A level of NLRP3 mRNA following miR-1208 targeted binding to METTL3, resulting in decreased inflammatory factor release and preventing OA progression. CONCLUSION: This study concluded that hucMSCs-EVs inhibited the secretion of pro-inflammatory factors and the degradation of cartilage ECM after lowering the m6A level of NLRP3 mRNA with miR-1208 targeting combined with METTL3, thereby alleviating OA progression in mice and providing a novel therapy for clinical OA treatment.

Efficacy of a WeChat-based intervention for adherence to secondary prevention therapies in patients undergoing coronary artery bypass graft in China: A randomized controlled trial.

INTRODUCTION: We assessed whether the social media-based (WeChat) intervention integrated with follow-up care could improve adherence to drugs, lifestyle changes and clinical risk markers in patients undergoing coronary artery bypass graft (CABG) in China. METHODS: We randomized patients at hospital discharge following CABG to intervention group or control care in China. The intervention is a structured programme of cardiac health education, medication reminders and cardiologist-based follow-up service using WeChat platform. The control group maintains a routine practice pattern. The primary outcome is adherence to cardioprotective medications measured for 12 months after discharge. We also evaluated the lifestyle modifications and clinical risk markers at 12 months. RESULTS: A total of 164 participants completed the trial for analysis. The intervention group had significantly greater adherence to statins use 98.6% vs. 75.0% (p < 0.01), beta-blockers 93.4% vs. 69.3% (p < 0.01) and aspirin 98.8% vs. 87.8% (p < 0.001). The intervention group had significantly greater adherence to regular physical activity (64.2% vs. 48.2%; p < 0.039). Furthermore, intervention versus standard group at 12 months had significantly lower mean systolic blood pressure and low-density lipoprotein cholesterol (p < 0.05). DISCUSSION: A WeChat-based intervention strategy in post-CABG patients improved adherence to medications, including statin, aspirin and beta-blockers, and regular physical activity and resulted in an improvement in systolic blood pressure and low-density lipoprotein cholesterol level.

Alkyl Hydroperoxide Reductase as a Determinant of Parasite Antiperoxide Response in Toxoplasma gondii.

Toxoplasma gondii is a protozoan parasite that is widely parasitic in the nucleated cells of warm-blooded animals. Bioinformatic analysis of alkyl hydroperoxide reductase 1 (AHP1) of T. gondii is a member of the Prxs family and exhibits peroxidase activity. Cys166 was certified to be a key enzyme active site of TgAHP1, indicating that the enzyme follows a cysteine-dependent redox process. TgAHP1 was present in a punctate staining pattern anterior to the T. gondii nucleus. Oxidative stress experiments showed that the ∆Ahp1 strain was more sensitive to tert-butyl hydroperoxide (tBOOH) than hydrogen peroxide (H2O2), indicating that tBOOH may be a sensitive substrate for TgAHP1. Under tBOOH culture conditions, the ∆Ahp1 strain was significantly less invasive, proliferative, and pathogenic in mice. This was mainly due to the induction of tBOOH, which increased the level of reactive oxygen species in the parasites and eventually led to apoptosis. This study shows that TgAHP1 is a peroxisomes protein with cysteine-dependent peroxidase activity and sensitive to tBOOH.

Impact of Conventional Cardiovascular Risk Factors on Left Internal Mammary Artery Graft Disease.

BACKGROUND: The development of atherosclerosis was considered as the common cause of the stenosis of coronary artery grafts. Left internal mammary artery (LIMA) was the best artery graft for further effectiveness of coronary artery bypass grafting (CABG). We sought to assess the impact of known conventional cardiovascular risk factors (RFs) on LIMA graft stenosis. METHODS: A retrospective study including 618 participants, who had recurrence of chest pain after CABG, aged ≥18 years, hospitalized for coronary angiography in Beijing Anzhen hospital between 2010 and 2017 was performed. All the participants were confirmed to have LIMA graft. Multivariate analysis was conducted to determine the relationship between conventional RFs and LIMA graft stenosis. RESULTS: Of the study, 220 (35.6%) participants continued to smoke, 504 (81.6%) were overweight or obese, and 411 (66.5%) and 242 (39.2%) reported concomitant hypertension and diabetes, respectively. LIMA graft stenosis occurred in 161 participants (26.1%). Postoperative smoking, a CABG duration of ≥10 years and hyperglycemia without diabetes had an increased risk of LIMA graft stenosis, the odds ratio (OR) was 1.86 [95% confidence interval (CI): 1.26-2.78], 2.24 (95%CI:1.33-3.478), and 2.44(95% CI:1.39-4.32), respectively. Statin use (OR, 0.28; 95% CI: 0.25-0.5) and low-density lipoprotein cholesterol (LDL-C) < 1.8 mmol/L (OR, 0.27; 95% CI: 0.14-0.53) had a significantly decreased risk of LIMA graft stenosis. While, only 15.4% (95/618) achieved the target LDL-C level. CONCLUSIONS: Postoperative smoking and hyperglycemia without diabetes had an increased risk of LIMA graft stenosis. Statin use and LDL-C <1.8 mmol/L decreased the risk.

AcMNPV-miR-3 is a miRNA encoded by Autographa californica nucleopolyhedrovirus and regulates the viral infection by targeting ac101.

MicroRNAs (miRNAs), which are small noncoding RNAs found in plants, animals, and many viruses, regulate various biological processes. Our group has previously reported the first miRNA encoded by Autographa californica multiple Nucleopolyhedrovirus (AcMNPV), AcMNPV-miR-1, which regulates the expression of three viral genes. This study characterizes another miRNA encoded by AcMNPV, AcMNPV-miR-3. This miRNA is located on the opposite strand of the viral gene ac101 coding sequence in the AcMNPV genome, and it can be detected at 6 h post-infection and accumulated to a peak around 12 h post-infection in AcMNPV infected Sf9 cells. Five viral genes (ac101, ac23, ac25, ac86, and ac98) were verified to be regulated by AcMNPV-miR-3. Ac101 was markedly down-regulated by AcMNPV-miR-3 that may be via a siRNA-like cleavage mode. Administrating excessive AcMNPV-miR-3 resulted in decreased production of infectious budded virions (BV) and accelerated the formation of occlusion-derived virions (ODV). These results suggest that AcMNPV-miR-3 may play a regulatory role in BV and ODV production.

Clinical characteristics and prognosis of acute myocardial infarction in young smokers and non-smokers (≤ 45 years): a systematic review and meta-analysis.

The effect of smoking on the prognosis of young patients with acute myocardial infarction (AMI) is inconclusive. We enrolled 2188 young AMI patients (≤ 45 years) from the cardiac center of the Chinese PLA General Hospital and Anzhen Hospital and analyzed their clinical characteristics and prognosis. We also searched the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials electronic databases for January 2001 to March 2017 and considered for inclusion in a meta-analysis those clinical trials that compared prognoses of young smokers and non-smokers with AMI. The proportion of males and alcohol users was higher in young AMI smokers than in non-smokers; the proportion of hypertension was slightly lower. There was no difference in medical treatment between smokers and non-smokers. No differences were evident between smokers and non-smokers regarding in-hospital cardiac events and major adverse cardiovascular events on follow-up, including incidence of stroke. For young AMI patients, smoking did not lead to poorer prognosisin comparison with not smoking. This "smoker's paradox" needs to be confirmed by more randomized controlled multicenter prospective clinical trials.

Trend in young coronary artery disease in China from 2010 to 2014: a retrospective study of young patients ≤ 45.

BACKGROUND: The incidence of young coronary heart disease (CHD, ≤45 years) in China is increasing. Secondary prevention to counter this trend is an important contemporary public health issure. METHODS: A total of 5288 patients (≤45 years) diagnosed with CHD and hospitalized at the Chinese PLA General Hospital and Anzhen Hospital, both in Beijing, were enrolled after satisfying the inclusion criteria. RESULTS: Young CHD patients increased in number from 2010 to 2014, especially men. Among the studied patients, there was no significant change over those years in blood pressure, but heart rate increased significantly (P < 0.05) and body mass index showed a rising trend (P > 0.05). The incidence of hypertension increased from 40.7 to 47.5%, diabetes from 20.3 to 26.1%, and hyperlipidemia from 27.3 to 35.7% (P < 0.05). However, the incidences of smoking and drinking both trended downward (P < 0.05). The levels of total cholesterol and triglycerides also showed a downward trend (P < 0.05), as did levels of low-density lipoprotein, but not to the point of statistical significance (P > 0.05). Mortality during hospitalization decreased significantly from 2010 to 2014 (P < 0.05), but there was no significant improvement in the incidences of cardiac death and major adverse cardiovascular events (MACE) after 1-year follow-up (P > 0.05). CONCLUSIONS: Over the 5 years studied, the overall incidence of cardiac death and MACE for young CHD patients (≤45 years) has shown little improvement. Secondary prevention of young CHD, and its risk factors, as well as appropriate courses of medical treatment must be further elucidated.

Functional Regulation of an Autographa californica Nucleopolyhedrovirus-Encoded MicroRNA, AcMNPV-miR-1, in Baculovirus Replication.

UNLABELLED: An Autographa californica nucleopolyhedrovirus-encoded microRNA (miRNA), AcMNPV-miR-1, downregulates the ac94 gene, reducing the production of infectious budded virions and accelerating the formation of occlusion-derived virions. In the current study, four viruses that constitutively overexpress AcMNPV-miR-1 were constructed to further explore the function of the miRNA. In addition to the ac94 gene, two new viral gene targets (ac18 and ac95) of AcMNPV-miR-1 were identified, and the possible interacting proteins were verified and tested. In the context of AcMNPV-miR-1 overexpression, ac18 was slightly upregulated, and ac95 was downregulated. Several interacting proteins were identified, and a functional pathway for AcMNPV-miR-1 was deduced. AcMNPV-miR-1 overexpression decreased budded virus infectivity, reduced viral DNA replication, accelerated polyhedron formation, and promoted viral infection efficiency in Trichoplusia ni larvae, suggesting that AcMNPV-miR-1 restrains virus infection of cells but facilitates virus infection of larvae. IMPORTANCE: Recently, microRNAs (miRNAs) have been widely reported as moderators or regulators of mammalian cellular processes, especially disease-related pathways in humans. However, the roles played by miRNAs encoded by baculoviruses, which infect numerous beneficial insects and agricultural pests, have rarely been described. To explore the actions of virus-encoded miRNAs, we investigated an miRNA encoded by Autographa californica nucleopolyhedrovirus (AcMNPV-miR-1). We previously identified this miRNA through the exogenous addition of AcMNPV-miR-1 mimics. In the current study, we constitutively overexpressed AcMNPV-miR-1 and analyzed the resultant effects to more comprehensively assess what is indeed the function of this miRNA during viral infection. In addition, we widely explored the target genes for the miRNA in the viral and host genomes and proposed a possible functional network for AcMNPV-miR-1, which provides a better general understanding of virus-encoded miRNAs. In brief, our study implied that AcMNPV-miR-1 constrains viral replication and cellular infection but enhances larval infection.

Autographa californica multiple nucleopolyhedrovirus gene ac81 is required for nucleocapsid envelopment.

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is a highly pathogenic Baculoviridae that targets insects, whose core gene, ac81, has an unknown function. To determine the role of ac81 in the life cycle of AcMNPV, an ac81-knockout (Ac-81KO-GP) was constructed through homologous recombination in Escherichia coli. We determined that no budded virions were produced in Ac-81KO-GP-transfected Sf9 cells, while there was no effect on viral DNA replication. Electron microscopy (EM) analysis revealed that occlusion-derived virions (ODVs) envelopment and the subsequent embedding of virions into occlusion bodies (OBs) were aborted due to ac81 deletion. Interestingly, confocal microscopy and immunofluorescence analysis revealed that Ac81 was predominantly localized to the ring zone of nuclei during the late phase of infection. In addition, Ac81 was localized to the mature and premature ODVs in virus-infected cells within the ring zone as revealed by immuno-electron microscopy (IEM) analysis. Furthermore, we determined that Ac81 contained a functional hydrophobic transmembrane (TM) domain, whose deletion resulted in a phenotype similar to that of Ac-81KO-GP. These results suggest that Ac81 might be a TM protein that played an important role in nucleocapsid envelopment.

Gender-specific associations of sleep duration with uncontrolled blood pressure in middle-aged patients.

OBJECTIVE: The present study was designed to evaluate the associations between sleep duration and uncontrolled blood pressure in a hospital-based sample of middle-aged adults. METHODS: Between March 2012 and December 2012, a cross-sectional survey was conducted among the hypertensive outpatients of Anzhen Hospital and a community hospital in Beijing, China. Eligible participants were adults aged 35-55 years with an established diagnosis of hypertension and had been on standard antihypertensive drug treatment for at least 6 months. An interviewer-led questionnaire was used to collect the participants' demographic, lifestyle and dietary information, as well as medical histories. Usual sleep durations were categorized as <7 h, 7-8 h and >8 h per night. Logistic regression models were used to assess gender-specific associations between sleep duration and uncontrolled hypertension, with adjustment for age, gender, family history, diabetes, smoking, alcohol consumption and physical activity. RESULTS: A total of 3038 participants were finally investigated. Among them, 1569 (51.6%) patients had their blood pressure uncontrolled. In men, no significant association was found between sleep duration categories and uncontrolled hypertension. In women, compared with those sleeping <7 h, longer sleepers tended to have a lower risk of uncontrolled hypertension for sleeping 7-8 hours (odds ratio [OR] 0.537, 95% confidence interval [CI], 0.370-0.780) and sleeping >8 h (OR 0.316, 95% CI, 0.202-0.494), respectively. CONCLUSION: Modest associations between short sleep duration and uncontrolled hypertension were seen in middle-aged women but not in men in the hypertensive population.

Association of serum cotinine levels and the parameters of vascular structure and function in never-smoking adults.

Passive smoking is now recognized to be associated with early arterial damage. The aim of this study was to assess the relationship between secondhand smoke (SHS) exposure, measured objectively by serum cotinine level, and the parameters used to assess vascular structure and function among never smokers in North China. From January 2008 to August 2008, 652 adults aged 20-70 years were enrolled. Brachial-ankle pulse wave velocity (baPWV), ankle-brachial index, and carotid intima-media thickness measurements were performed in all patients. All participants were required to respond to an interviewer-led questionnaire including medical histories and demographic data and to receive blood tests on biochemical indicators. We found that in nonsmokers, higher levels of serum cotinine were positively associated with higher baPWV and brachial pulse pressure after adjusting for heart rate, body mass index, and other confounders. Tests for linear trends for this association were statistically significant. In contrast, no association was present with ankle-brachial index and carotid intima-media thickness. In never smokers, higher SHS exposure measured objectively by serum cotinine levels was found to be associated with brachial pulse pressure and baPWV after adjusting for confounders.

A microRNA encoded by Autographa californica nucleopolyhedrovirus regulates expression of viral gene ODV-E25.

Baculovirus-encoded microRNAs (miRNAs) have been described in Bombyx mori nucleopolyhedrovirus; however, most of their functions remain unclear. Here we report the identification and characterization of an miRNA encoded by Autographa californica nucleopolyhedrovirus. The identified miRNA, AcMNPV-miR-1, perfectly matched a segment in the coding sequence of the viral gene ODV-E25 and downregulated ODV-E25 mRNA expression, which likely resulted in a reduction of infectious budded virions and accelerated the formation of occlusion-derived virions.

Prevalence of arterial stiffness in North China, and associations with risk factors of cardiovascular disease: a community-based study.

BACKGROUND: Brachial-ankle pulse wave velocity (baPWV), which reflects the stiffness of both central and peripheral muscular arteries, has been frequently used as a simple index for assessing arterial stiffness. The aim of the present study was to investigate the prevalence of arterial stiffness in North China based on baPWV measurements, and explore the associations between increased arterial stiffness and risk factors of cardiovascular diseases (CVD). METHODS: Twenty-three community populations were established in North China. For each participant, parameters for calculating baPWV, including blood pressures and pressure waveforms, were measured using a non-invasive automatic device. All participants were required to respond to an interviewer-led questionnaire including medical histories and demographic data, and to receive blood tests on biochemical indictors. RESULTS: A total of 2,852 participants were finally investigated. Among them, 1,201 people with low burden of CVD risk factors were chosen to be the healthy reference sample. The cut-off point of high baPWV was defined as age-specific 90th percentile of the reference sample. Thus, the prevalence of high baPWV was found to be 22.3% and 26.4% in men and women respectively. After adjusted for age, heart rate (HR), systolic blood pressure (SBP), fasting glucose level, and smoking were significantly associated with high baPWV in men; while level of serum total cholesterol (TC), HR, SBP, and diabetes were significantly associated with high baPWV in women. CONCLUSIONS: Based on the age-specific cut-off points, the middle-aged population has a higher prevalence of high baPWV in North China. There exists a difference between men and women in terms of the potential risk factors associated with arterial stiffness.

Histone deacetylase 1 is required for Carbamazepine-induced CYP3A4 expression.

Carbamazepine (CBZ) is a commonly prescribed antiepileptic drug. Adverse effects and drug-drug interaction are the two major concerns for its clinic application. CBZ is mainly metabolized by cytochrome P450 (CYP) 3A4, a strong inducer of CYP3A4 as well, which in turn influences the pharmaceutical profiles of the co-administrated drugs. To date, little is known about the mechanisms underlying CBZ-induced CYP3A4 expression. In this study, we explored the possible roles of Pregnane X receptor (PXR) and the histone deacetylase 1 (HDAC1) on the CBZ-induced CYP3A4 expression. The results showed that: (1) Although the expression of PXR was increased in CBZ treated cells, PXR gene silencing surprisingly showed no significant effects on CBZ-induced CYP3A4 expression; (2) CBZ inhibited the binding of HDAC1 to the promoter of CYP3A4. In addition, both dominant negative form and siRNA of HDAC1 could repress the CBZ-induced CYP3A4 expression. These data, for the first time indicate that HDAC1, is required for the CBZ-induced CYP3A4 expression.