LINC08148 promotes the caveola-mediated endocytosis of Zika virus through upregulating transcription of Src.

Long non-coding RNAs (lncRNAs) represent a new group of host factors involved in viral infection. Current study identified an intergenic lncRNA, LINC08148, as a proviral factor of Zika virus (ZIKV) and Dengue virus 2 (DENV2). Knockout (KO) or silencing of LINC08148 decreases the replication of ZIKV and DENV2. LINC08148 mainly acts at the endocytosis step of ZIKV but at a later stage of DENV2. RNA-seq analysis reveals that LINC08148 knockout downregulates the transcription levels of five endocytosis-related genes including AP2B1, CHMP4C, DNM1, FCHO1, and Src. Among them, loss of Src significantly decreases the uptake of ZIKV. Trans-complementation of Src in the LINC08148KO cells largely restores the caveola-mediated endocytosis of ZIKV, indicating that the proviral effect of LINC08148 is exerted through Src. Finally, LINC08148 upregulates the Src transcription through associating with its transcription factor SP1. This work establishes an essential role of LINC08148 in the ZIKV entry, underscoring a significance of lncRNAs in the viral infection. IMPORTANCE: Long non-coding RNAs (lncRNAs), like proteins, participate in viral infection. However, functions of most lncRNAs remain unknown. In this study, we performed a functional screen based on microarray data and identified a new proviral lncRNA, LINC08148. Then, we uncovered that LINC08148 is involved in the caveola-mediated endocytosis of ZIKV, rather than the classical clathrin-mediated endocytosis. Mechanistically, LINC08148 upregulates the transcription of Src, an initiator of caveola-mediated endocytosis, through binding to its transcription factor SP1. This study identifies a new lncRNA involved in the ZIKV infection, suggesting lncRNAs and cellular proteins are closely linked and cooperate to regulate viral infection.

Exploring the efficacy and beneficial population of preimplantation genetic testing for aneuploidy start from the oocyte retrieval cycle: a real-world study.

BACKGROUND: Preimplantation genetic testing for aneuploidy (PGT-A) is widely used as an embryo selection technique in in vitro fertilization (IVF), but its effectiveness and potential beneficiary populations are unclear. METHODS: This retrospective cohort study included patients who underwent their first oocyte retrieval cycles at CITIC-Xiangya between January 2016 and November 2019, and the associated fresh and thawed embryo transfer cycles up to November 30, 2020. PGT-A (PGT-A group) and intracytoplasmic sperm injection (ICSI)/IVF (non-PGT-A group) cycles were included. The numbers of oocytes and embryos obtained were unrestricted. In total, 60,580 patients were enrolled, and baseline data were matched between groups using 1:3 propensity score matching. Sensitivity analyses, including propensity score stratification and traditional multivariate logistic regression, were performed on the original unmatched cohort to check the robustness of the overall results. Analyses were stratified by age, body mass index, ovarian reserve/responsiveness, and potential indications to explore benefits in subgroups. The primary outcome was cumulative live birth rate (CLBR). The other outcomes included live birth rate (LBR), pregnancy loss rate, clinical pregnancy rate, pregnancy complications, low birth weight rate, and neonatal malformation rate. RESULTS: In total, 4195 PGT-A users were matched with 10,140 non-PGT-A users. A significant reduction in CLBR was observed in women using PGT-A (27.5% vs. 31.1%; odds ratio (OR) = 0.84, 95% confidence interval (CI) 0.78-0.91; P < 0.001). However, women using PGT-A had higher first-transfer pregnancy (63.9% vs. 46.9%; OR = 2.01, 95% CI 1.81-2.23; P < 0.001) and LBR (52.6% vs. 34.2%, OR = 2.13, 95% CI 1.92-2.36; P < 0.001) rates and lower rates of early miscarriage (12.8% vs. 20.2%; OR = 0.58, 95% CI 0.48-0.70; P < 0.001), preterm birth (8.6% vs 17.3%; P < 0.001), and low birth weight (4.9% vs. 19.3%; P < 0.001). Moreover, subgroup analyses revealed that women aged ≥ 38 years, diagnosed with recurrent pregnancy loss or intrauterine adhesions benefited from PGT-A, with a significant increase in first-transfer LBR without a decrease in CLBR. CONCLUSION: PGT-A does not increase and decrease CLBR per oocyte retrieval cycle; nonetheless, it is effective in infertile populations with specific indications. PGT-A reduces complications associated with multiple gestations.

Behavioral abnormalities in C57BL/6 mice with chronic ulcerative colitis induced by DSS.

BACKGROUND: Clinical epidemiological studies have found that some patients with ulcerative colitis (UC) are prone to mental disorders. DSS-induced acute and chronic UC models are often used to evaluate the efficacy of anti-UC drugs. However, whether DSS has an effect on mouse behavior has not been reported. METHODS: Acute and chronic UC models were induced by 3% DSS and 1.5% DSS, respectively. The bloody stool, the changes in the colon length, and histopathological changes in the colon were used to evaluate the success of the animal model. The behavior of mice was evaluated by open field experiment, tail suspension experiment and Sucrose preference test. RESULTS: The weight of mice in 3% DSS group decreased significantly, the DAI score increased significantly, the colon length of mice was significantly shortened, and the structure of colonic crypts was abnormal, which showed inflammatory cell infiltration and shrinkage of crypts. Compared with the control group, the immobility time of 3%DSS group mice in the tail suspension test and forced swimming test had no effect, the number of running and grooming times was significantly reduced, and there was no significant difference in the number of standing times. No abnormality was observed in HE staining of the hippocampus. However, in 1.5% DSS-induced chronic UC model, behavioral and hippocampal abnormalities were observed not only UC symptoms. CONCLUSIONS: The acute UC model induced by 3% DSS has certain influence on the behavior of mice, but the mental state of mice is normal, which may be the abnormal behavior caused by UC symptoms; However, the chronic UC model induced by 1.5% DSS has a significant effect on the behavior of mice, and the mice have mental disorders, which are caused by mental disorders.

An AQI decomposition ensemble model based on SSA-LSTM using improved AMSSA-VMD decomposition reconstruction technique.

Air quality index (AQI) is a key index for monitoring air pollution and can be used as guide for ensuring good public health. Accurate AQI prediction allows timely control and management of air pollution. In this study, a new integrated learning model was constructed to predict AQI. A smart reverse learning approach based on AMSSA was utilized to increase the diversity of populations, and an improved AMSSA (IAMSSA) was established. The optimum parameters with penalty factor α and mode number K of VMD were obtained using IAMSSA. The IAMSSA-VMD was used to decompose nonlinear and non-stationary AQI information series into several regular and smooth sub-sequences. The Sparrow Search Algorithm (SSA) was used to determine the optimum LSTM parameters. The results showed that: (1) IAMSSA exhibits faster convergence and higher accuracy and stability using simulation experiments compared with seven conventional optimization algorithms in 12 test functions. (2) IAMSSA-VMD was used to decompose the original air quality data results in multiple uncoupled intrinsic mode function (IMF) components and one residual (RES). An SSA-LSTM model was built for each IMF and one RES component, which effectively extracted the predicted values. (3) LSTM, SSA-LSTM, VMD-LSTM, VMD-SSA-LSTM, AMSSA-VMD-SSA-LSTM, and IAMSSA-VMD-SSA-LSTM models were used for prediction of AQI based on data from three cities (Chengdu, Guangzhou, and Shenyang). IAMSSA-VMD-SSA-LSTM exhibited the optimal prediction performance with MAE, RMSE, MAPE, and R2 of 3.692, 4.909, 6.241, and 0.981, respectively. (4) Generalization outcomes revealed that the IAMSSA-VMD-SSA-LSTM model had optimal generalization ability. In summary, the decomposition ensemble model proposed in this study has higher prediction accuracy, improved fitting effect and generalization ability compared with other models. These properties indicate the superiority of the decomposition ensemble model and provides a theoretical and technical basis for prediction of air pollution and ecosystem restoration.

Primary root response to combined drought and heat stress is regulated via salicylic acid metabolism in maize.

The primary root is the first organ to perceive the stress signals for abiotic stress. In this study, maize plants subjected to drought, heat and combined stresses displayed a significantly reduced primary root length. Metabolic and transcriptional analyses detected 72 and 5,469 differentially expressed metabolites and genes in response to stress conditions, respectively. The functional annotation of differentially expressed metabolites and genes indicated that primary root development was mediated by pathways involving phenylalanine metabolism, hormone metabolism and signaling under stress conditions. Furthermore, we found that the concentration of salicylic acid and two precursors, shikimic acid and phenylalanine, showed rapid negative accumulation after all three stresses. The expression levels of some key genes involved in salicylic acid metabolism and signal transduction were differentially expressed under stress conditions. This study extends our understanding of the mechanism of primary root responses to abiotic stress tolerance in maize.

[Effect and mechanism of Jingqi Yukui Capsules on gastric ulcer mucosa healing quality: based on network pharmacology and animal experiment].

This study aims to identify the active components and the mechanism of Jingqi Yukui Capsules(JQYK) in the treatment of gastric ulcer based on network pharmacology, and verify some key targets and signaling pathways through animal experiment. To be specific, first, the active components and targets of JQYK were retrieved from a Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets of gastric ulcer from GeneCards and Online Mendelian Inheritance in Man(OMIM) with the search term "gastric ulcer". The common targets of the two were the potential targets of the prescription for the treatment of the di-sease. Then, protein-protein interaction(PPI) network of key targets were constructed based on STRING and Cytoscape 3.7.2, followed by Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by matescape database and pathway visualization by Omicshare. For the animal experiment, the improved method of Okabe was used to induce gastric ulcer in rats, and the model rats were classified into the model group, JQYK high-dose(JQYK-H), medium-dose(JQYK-M), and low-dose(JQYK-L) groups, Anweiyang Capsules(WYA) group, and Rabeprazole Sodium Enteric Capsules(RBPZ) group. Normal rats were included in the blank group. Rats in the blank group and model group were given distilled water and those in the administration groups received corresponding drugs. Then gastric ulcer healing in rats was observed. The changes of the gastric histomorphology in rats were evaluated based on hematoxylin-eosin(HE) staining, and the content of inducible nitric oxide synthase(iNOS) in rat gastric tissue was detected with Coomassie brilliant blue method. The mRNA and protein levels of some proteins in rat gastric tissue were determined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot(WB) to further validate some key targets and signaling pathways. A total of 206 active components and 535 targets of JQYK, 1 305 targets of gastric ulcer, and 166 common targets of the disease and the drug were yielded. According to PPI analysis and KEGG pathway enrichment analysis, multiple key targets, such as interleukin-6(IL-6), tumor necrosis factor(TNF), mitogen-activated protein kinase 1(MAPK1), MAPK3, and MAPK14, as well as nuclear factor kappa-B(NF-κB) signaling pathway, IL-17 signaling pathway, and leukocyte transendothelial migration in the top 20 key signaling pathways were closely related to inflammation. The key protein p38 MAPK and NF-κB signaling pathway were selected for further verification by animal experiment. The gastric ulcer in the JQYK-H group recovered nearly to the level in the blank group, with significant decrease in the content of iNOS in rat gastric tissue and significant reduction in the mRNA and phosphorylation levels of p38 MAPK and the mRNA and protein levels of NF-κB p65 in rat gastric tissue. The results indicated that JQYK can inhibit the phosphorylation of the key protein p38 MAPK and the expression of NF-κB p65 in the NF-κB signaling pathway, thereby exerting the anti-inflammatory effect and effectively improving the quality of gastric ulcer healing in rats. Thus, the animal experiment result verifies some predictions of network pharmacology.

Regenerative responses of rabbit corneal endothelial cells to stimulation by fibroblast growth factor 1 (FGF1) derivatives, TTHX1001 and TTHX1114.

Utilising rabbit corneal endothelial cells (CEC) in three different paradigms, two human FGF1 derivatives (TTHX1001 and TTHX1114), engineered to exhibit greater stability, were tested as proliferative agents. Primary CECs and mouse NIH 3T3 cells treated with the two FGF1 derivatives showed equivalent EC50 ranges (3.3-24 vs.1.9-16. ng/mL) and, in organ culture, chemically lesioned corneas regained half of the lost endothelial layer in three days after treatment with the FGF1 derivatives as compared to controls. In vivo, following cryolesioning, the CEC monolayer, as judged by specular microscopy, regenerated 10-11 days faster when treated with TTHX1001. Over two weeks, all treated eyes showed clearing of opacity about twice that of untreated controls. In all three rabbit models, both FGF1 derivatives were effective in inducing CEC proliferation over control conditions, supporting the prediction that these stabilised FGF1 derivatives can potentially regenerate corneal endothelial deficits in humans.

Exploiting natural variation in crown root traits via genome-wide association studies in maize.

BACKGROUND: Root system architecture (RSA), which is determined by the crown root angle (CRA), crown root diameter (CRD), and crown root number (CRN), is an important factor affecting the ability of plants to obtain nutrients and water from the soil. However, the genetic mechanisms regulating crown root traits in the field remain unclear. METHODS: In this study, the CRA, CRD, and CRN of 316 diverse maize inbred lines were analysed in three field trials. Substantial phenotypic variations were observed for the three crown root traits in all environments. A genome-wide association study was conducted using two single-locus methods (GLM and MLM) and three multi-locus methods (FarmCPU, FASTmrMLM, and FASTmrEMMA) with 140,421 SNP. RESULTS: A total of 38 QTL including 126 SNPs were detected for CRA, CRD, and CRN. Additionally, 113 candidate genes within 50 kb of the significant SNPs were identified. Combining the gene annotation information and the expression profiles, 3 genes including GRMZM2G141205 (IAA), GRMZM2G138511 (HSP) and GRMZM2G175910 (cytokinin-O-glucosyltransferase) were selected as potentially candidate genes related to crown root development. Moreover, GRMZM2G141205, encoding an AUX/IAA transcriptional regulator, was resequenced in all tested lines. Five variants were identified as significantly associated with CRN in different environments. Four haplotypes were detected based on these significant variants, and Hap1 has more CRN. CONCLUSIONS: These findings may be useful for clarifying the genetic basis of maize root system architecture. Furthermore, the identified candidate genes and variants may be relevant for breeding new maize varieties with root traits suitable for diverse environmental conditions.

Integrating transcriptome, co-expression and QTL-seq analysis reveals that primary root growth in maize is regulated via flavonoid biosynthesis and auxin signal transduction.

The primary root is critical for early seedling growth and survival. To understand the molecular mechanisms governing primary root development, we performed a dynamic transcriptome analysis of two maize (Zea mays) inbred lines with contrasting primary root length at nine time points over a 12-day period. A total of 18 702 genes were differentially expressed between two lines or different time points. Gene enrichment, phytohormone content determination, and metabolomics analysis showed that auxin biosynthesis and signal transduction, as well as the phenylpropanoid and flavonoid biosynthesis pathways, were associated with root development. Co-expression network analysis revealed that eight modules were associated with lines/stages, as well as primary or lateral root length. In root-related modules, flavonoid metabolism accompanied by auxin biosynthesis and signal transduction constituted a complex gene regulatory network during primary root development. Two candidate genes (rootless concerning crown and seminal roots, rtcs and Zm00001d012781) involved in auxin signaling and flavonoid biosynthesis were identified by co-expression network analysis, QTL-seq and functional annotation. These results increase our understanding of the regulatory network controlling the development of primary and lateral root length, and provide a valuable genetic resource for improvement of root performance in maize.

Genetic control of root plasticity in response to salt stress in maize.

KEY MESSAGE: GWAS identified 559 significant SNPs associated with the remodelling of the root architecture in response to salt, and 168 candidate genes were prioritized by integrating RNA-seq, DEG and WGCNA data. Salinity is a major environmental factor limiting crop growth and productivity. The root is the first plant organ to encounter salt stress, yet the effects of salinity on maize root development remain unclear. In this study, the natural variations in 14 root and 4 shoot traits were evaluated in 319 maize inbred lines under control and saline conditions. Considerable phenotypic variations were observed for all traits, with high salt concentrations decreasing the root length, but increasing the root diameter. A genome-wide association study was conducted to analyse these traits and their plasticity (relative variation). We detected 559 significant single nucleotide polymorphisms, of which 125, 181 and 253 were associated with the control condition, stress condition and trait plasticity, respectively. A total of 168 of 587 candidate genes identified by genome-wide association study were supported by the differentially expressed genes or co-expression networks. Two candidate genes ZmIAA1 and ZmGRAS43 were validated by resequencing. Among these genes, 130 were detected under stress condition or trait plasticity that involved in diverse biological processes including plant hormone signal transduction, phenylpropanoid biosynthesis and fatty acid biosynthesis. Our findings clarify the root remodelling to salinity, and the identified loci and candidate genes may be important for the genetic improvement of root traits and salt tolerance in maize.

Health damage to housewives by contaminants emitted from coal combustion in the Chinese countryside: focusing on day-to-day cooking.

PURPOSE: The study aimed to estimate the health damage and find out the main exposure pathways of housewives posed by polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) from coal combustion in rural areas of China. METHODS: We obtained the concentrations of 16 PAHs and 8 HMs from published literatures and the Monte Carlo simulation was used to process and analysis the data. Sensitivity analysis was also applied to clear parameter uncertainty and the health damage of housewives was quantitatively evaluated by loss of life expectancy. RESULTS: Housewives' carcinogenic risks from PAHs exposure were in descending order of inhalation > ingestion > dermal contact, while exposed to HMs were ingestion > dermal contact > inhalation. The carcinogenic risks from PAHs primarily originated from benzo[a]pyrene (BaP), dibenz[ah]anthracene (DahA) and benzo[b]fluorathene (BbF). For HMs, arsenic posed the highest carcinogenic risk to housewives, with a contribution of 92.98%. In addition, the life expectancy loss of housewives exposed to PAHs was 469.04 min from inhalation and 51.82 min for HMs from ingestion. CONCLUSION: Through a comprehensive assessment of the health risks in housewives exposed to emissions from coal combustion, we can gain insight into the hazards from PAHs and HMs in housewives, and take measures to reduce their exposure risks.

Physical activity and atrial tachyarrhythmia recurrence in atrial fibrillation patients after catheter ablation.

BACKGROUND: The association between physical activity (PA) and atrial tachyarrhythmia (AT) recurrence after ablation for atrial fibrillation (AF) remains unclear. METHODS: We consecutively enrolled 496 patients treated with AF ablation therapy in Beijing Anzhen Hospital. After excluding six patients with valvular heart disease, seven patients with congenital heart disease, 33 patients lost to follow-up, and 14 patients who did not provide PA level during follow-ups, 436 patients had their PA level assessed by the International Physical Activity Questionnaire-Short Form before ablation and each time of follow-up. The association between PA level (measured at the time closest to AT recurrence, or the end of 12-month follow-up if no AT recurrence), as well as active PA during follow-up, and postablation AT recurrence was tested by multivariate logistic regression. RESULTS: Of the enrolled patients, 134 (30.7%) patients experienced AT recurrence in the first 12 months postablation. Compared to patients with low PA, patients with moderate or high PA had a lower risk of AT recurrence (odds ratio [OR] = .44; 95% confidence interval [CI], .25-.80; P = .01 for patients with moderate PA; and OR = .43 [95% CI, .21-.85], P = .02 for patients with high PA). Compared to patients without active PA, patients with active PA had a lower risk of AT recurrence (OR = .44 [95% CI, .27-.70], P < .01). CONCLUSIONS: Moderate and high PA are associated with a lower risk of AT recurrence after AF ablation. Active PA during follow-up is also associated with a significantly lower risk of AT recurrence in the postablation AF population.

Improved oral delivery of tilianin through lipid-polymer hybrid nanoparticles to enhance bioavailability.

Tilianin (TIL) may prevent and treat myocardial ischemia reperfusion injuries. However, its oral administration is hampered by its low bioavailability. The present study aimed to formulate lipid-polymer hybrid nanoparticles (LPHNs) as carriers for the sustained release and oral bioavailability enhancement of TIL in vitro and in vivo. A nanodrug delivery system of TIL-loaded LPHNs (TIL-LPHNs) was constructed. TIL-LPHNs were prepared via a self-assembly method, and their particle size, polymer dispersity index (PDI), zeta potential, encapsulation efficiency (EE) and morphology were investigated. In addition, pharmacokinetic studies were performed in vivo. The TIL-LPHN formulation produced a spherical, homogeneous, smooth surface and multi-lamellar structured nanoparticles. The particle size and distribution profile of TIL-LPHNs had a mean particle diameter of 54.6 ±â€¯5.3 nm and PDI of 0.112 ±â€¯0.017. The zeta potential was -33.4 ±â€¯4.7 mV. The EE of TIL-LPHNs was 86.6 ±â€¯3.6%, which was determined with the dialysis method. The TIL-LPHNs significantly enhanced the oral bioavailability of TIL with a 3.7-fold increase in the area under the concentration-time curve in comparison with the TIL solution. These findings support the potential use of LPHNs in improving the stability and bioavailability of TIL via oral administration.

Natural variation of ZmHKT1 affects root morphology in maize at the seedling stage.

MAIN CONCLUSION: Eight variants in ZmHKT1 promoter were significantly associated with root diameter, four haplotypes based on these significant variants were found, and Hap2 has the largest root diameter. Roots play an important role in uptake of water, nutrients and plant anchorage. Identification of gene and corresponding SNPs associated with root traits would enable develop maize lines with better root traits that might help to improve capacity for absorbing nutrients and water acquisition. The genomic sequences of a salt tolerance gene ZmHKT1 was resequenced in 349 maize inbred lines, and the association between nucleotide polymorphisms and seedling root traits was detected. A total of 269 variants in ZmHKT1 were identified, including 226 single nucleotide polymorphisms and 43 insertions and deletions. The gene displayed high level of nucleotide diversity, especially in non-genic regions. A total of 19 variations in untranslated region of ZmHKT1 were found to be associated with six seedling traits. Eight variants in promoter region were significantly associated with average root diameter (ARD), four haplotypes were found based on these significant variants, and Hap2 has the largest ARD. Two SNPs in high-linkage disequilibrium (SNP-415 and SNP 2169) with pleiotropic effects were significantly associated with plant height, root surface area, root volume, and shoot dry weight. This result revealed that ZmHKT1 was an important contributor to the phenotypic variations of seedling root traits in maize, these significant variants could use to develop functional markers to improve root traits.

Letrozole supplementation during controlled ovarian stimulation in expected high responders: a pilot randomized controlled study.

BACKGROUND: Almost all of the previous studies related with co-administration of letrozole in IVF cycles were performed in poor responders and letrozole may reduce the total gonadotropin dose required for ovarian stimulation, and the pregnancy rate did not decrease in poor responders. This study aimed to assess whether high responders co-treatment with letrozole reduced supraphysiological late follicular phase estradiol levels and the incidence of premature progesterone elevated at the end of the follicular phase, thereby impacting positively on endometrial receptivity. METHODS: A randomized parallel controlled study in a university-affiliated center include 130 high responders between October 2015 and August 2016. The patients were randomized on the first stimulation day of the IVF cycle and from stimulation day 5 receive letrozole (group A) or without letrozole treatment (group B). RESULTS: Although estradiol levels were significantly lower in the letrozole group (group A) (P < 0.001), progesterone elevation (> 1.5 ng/mL was considered as a rise) on the day of hCG triggering (15.4, 7.7%) was not statistically significant (P = 0.170). RecFSH, the recovery rate of eggs, the high-quality embryo rate, and the thickness of endometrium (P = 0.776) were similar between the letrozole group(group A) and control groups (group B). Clinical pregnancy rates were 53.1% (26/49) and 72.9% (35/48) in the letrozole and control groups, respectively, with a statistical significance (P = 0.043).Live birth rates were 42.9% (21/49) and 62.5% (30/48),showed a marginally significant difference (P = 0.053). The miscarriage rate did not significantly differ between the two groups. CONCLUSIONS: In this pilot study, letrozole supplementation could not reduce the incidence of premature progesterone rise during the late follicular phase in stimulated in vitro fertilization cycles in expected high responders, producing a harmful effect on the pregnancy outcome. TRIAL REGISTRATION: China Clinical Trial Registration Center: ChiCTR-IPR-15006211 URL of the trial registry record: http://www.chictr.org.cn/showproj.aspx?proj=10731 . Trial registration date: 8 April, 2015. Date of first patient's enrolment: 5 October, 2015.

Control of Anticoagulation Therapy in Patients with Atrial Fibrillation Treated with Warfarin: A Study from the Chinese Atrial Fibrillation Registry.

BACKGROUND Several factors determine the efficacy of warfarin anticoagulation in patients with non-valvular atrial fibrillation (NVAF). This study aimed to use data from the Chinese Atrial Fibrillation Registry study to assess the control of anticoagulation therapy in Chinese patients with NVAF treated with warfarin. MATERIAL AND METHODS From the Chinese Atrial Fibrillation Registry study the anticoagulant use and dosing, the time in therapeutic range (TTR) of the international normalized ratio (INR), and standard deviation of the observed INR values (SDINR), and their influencing factors were evaluated. RESULTS The median INR and SDINR were 2.04 (IQR 1.71-2.41) and 0.50 (IQR, 0.35-0.69), respectively. The median TTR was 51.7% (IQR, 30.6-70.1%) and only 25.1% had a TTR ≥70%. Age was ≥70 years (OR, 0.72; 95% CI, 0.55-0.94; P=0.015), bleeding history (OR 0.48; 95% CI, 0.23-0.89; P=0.029), the use of a single drug (OR, 0.62; 95% CI, 0.42-0.92; P=0.016), more than drug (OR, 0.60; 95% CI, 0.41-0.88; P=0.009), and lack of assessment of bleeding risk (OR, 0.72; 95% CI, 0.54-0.97; P=0.033) were associated with TTR <70% (INR 2.0-3.0). Coronary heart disease (CHD) and peripheral artery disease (PAD) (OR, 0.69; 95% CI, 0.52-0.90; P=0.007) and diabetes mellitus (OR, 0.79; 95% CI, 0.62-0.99; P=0.044) were associated with increased variability in INR (SDINR ≥0.5). CONCLUSIONS In Chinese patients with NVAF, warfarin anticoagulation was associated with lower TTR and less stable anticoagulation than in current guidelines, and risk factors for reduced safety and efficacy were identified.

Networks of E-cadherin, ß1 integrin, and focal adhesion kinase in the pathogenesis of tubal pregnancy.

E-cadherin, ß1 integrin, and focal adhesion kinase (FAK) are reported to involved in eutopic implantation by mediating cell adhesion. However, less is documented about their roles in ectopic implantation. This study was undertaken to evaluate the roles and networks of E-cadherin, ß1 integrin, and FAK in tubal pregnancy. A total of 31 Fallopian tube specimens were obtained from tubal pregnant women. Immunohistochemistry and western blot were used to analyze the distributions and levels of E-cadherin, ß1 integrin and phosphorylated-FAK (Pho-FAK) in the Fallopian tube epithelium. Normal Fallopian tube samples derived from non-pregnant women with benign genital diseases were used for comparison. E-cadherin presented in the cytomembrane of tubal epithelial cells and ß1 integrin mainly expressed in the cytoplasm. A lowest-level of E-cadherin was detected in the implantation site (0.63 ± 0.29) when compared with the non-implantation site (0.95 ± 0.37) and the controls (0.89 ± 0.33) (P < 0.05). ß1 integrin, as well as Pho-FAK in the implantation site (0.81 ± 0.35; 0.72 ± 0.24), showed a higher-level than that in the non-implantation site (0.59 ± 0.26; 0.48 ± 0.27) or the control group (0.38 ± 0.19; 0.36 ± 0.25) (p < .05). The decreased E-cadherin and increased ß1 integrin are implicated in tubal pregnancy. The involvement of ß1 integrin maybe depends on ß1 integrin/FAK signaling.

Dysregulated erythropoietin-producing hepatocellular receptor A2 (EphA2) is involved in tubal pregnancy via regulating cell adhesion of the Fallopian tube epithelial cells.

BACKGROUND: Tyrosine kinase receptor erythropoietin-producing hepatocellular receptor A2 (EphA2) is abundant in the endometrium and plays a role in the establishment of eutopic implantation. A similar molecular mechanism may exist between uterine implantation and tubal implantation, therefore EphA2 involvement in tubal pregnancy is suspected. Due to the limited availability of human Fallopian tube specimens, EphA2 expression in human Fallopian tube epithelium remains largely unknown. METHODS: A total of 31 women with tubal pregnancy and 41 non-pregnant women with benign uterine diseases were enrolled in this study. Immunohistochemistry was used to investigate the expression pattern of EphA2 in the Fallopian tube epithelium of non-pregnant women (n = 29) and women with tubal pregnancy (n = 17). The changes of EphA2 and its activated form, phosphorylated-EphA2 (Pho-EphA2), in the Fallopian tube epithelium from non-pregnant women (n = 12) and women with tubal pregnancy (n = 14) were compared by quantitative RT-PCR and western blot assay. RESULTS: EphA2 was expressed throughout the Fallopian tube epithelium, including the isthmus, the ampulla and the infundibulum. EphA2 concentration remained unchanged throughout the whole menstrual cycle, irrespective of menstrual phases and tubal regions. EphA2 mRNA in the Fallopian tube epithelium did not differ between normal women and women with tubal pregnancy (P > 0.05). With respect to the protein level, a significantly higher ratio of EphA2 over Pho-EphA2 was shown in women with tubal pregnancy (P < 0.05). CONCLUSIONS: EphA2 is widely expressed in human Fallopian tube epithelium in a temporospatial-independent manner. Dysregulated EphA2 and its phosphorylation-dependent regulatory mechanism may unexpectedly enhance the cell adhesion activity of the Fallopian tube epithelial cells, leading to a mis-contact between the Fallopian tube epithelium and the embryo.

Effects of the Kunlun snow chrysanthemum polysaccharides on acetaminophen-induced oxidative stress, inflammation and apoptosis using animal model.

To investigate the preventive effect of Kunlun snow chrysanthemum polysaccharides (KSCP) on acetaminophen (AP) induced liver damage and its possible mechanism. Mice acute liver injury model was established via intraperitoneal injection of AP (300 mg/kg). The biochemical indicators of plasma and liver tissue were tested. The effects of KSCP on the liver index were examined. The liver pathological changes were investigated. The expressions of related protein were detected via Western blotting. In our study, compared with model group, the concentrations and contents of ALT, AST, TNF-α, IL-1ß and MDA were reduced and activities of SOD were increase in H-KSCP (1.2mg/10 g)-pretreated mice (P<0.01). The liver index was significantly reduced in H-KSCP-pretreated mice compared with model group (4.89±0.22 vs 7.4±0.66, P<0.01). Liver cellular swelling, degeneration and necrosis relieved, and pathological injury had been improved. Western blotting results showed that the caspase-3 protein level in H-KSCP group was significantly decreased, expression of Bcl-2 protein and Bcl-2/Bax ratio was increased, whereas which of Bax protein was decreased (P<0.01). KSCP-pretreated at middle and high doses can prevent against the liver injury, its action mechanism may be related to its anti-inflammatory effects and regulation of apoptosis related proteins expression. Overall, our results showed that KSCP may be an effective preventive agent in preventing acute liver injury.

Adoptive Regulatory T-cell Therapy Attenuates Perihematomal Inflammation in a Mouse Model of Experimental Intracerebral Hemorrhage.

The CD4+CD25+ regulatory T cells (Tregs), an innate immunomodulator, suppress cerebral inflammation and maintain immune homeostasis in multiple central nervous system injury, but its role in intracerebral hemorrhage (ICH) has not been fully characterized. This study investigated the effect of Tregs on brain injury using the mouse ICH model, which is established by autologous blood infusion. The results showed that tail intravenous injection of Tregs significantly reduced brain water content and Evans blue dye extravasation of perihematoma at day (1, 3 and 7), and improved short- and long-term neurological deficits following ICH in mouse model. Tregs treatment reduced the content of pro-inflammatory cytokines interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, and malondialdehyde, while increasing the superoxide dismutase (SOD) enzymatic activity at day (1, 3 and 7) following ICH. Furthermore, Tregs treatment obviously reduced the number of NF-κB+, IL-6+, TUNEL+ and active caspase-3+ cells at day 3 after ICH. These results indicate that adoptive transfer of Tregs may provide neuroprotection following ICH in mouse models.