Effect of Remimazolam Supplementation on Propofol Requirements During Hysteroscopy: A Double-Blind, Dose-Response Study.

BACKGROUND: Propofol is commonly used for procedural sedation but may increase side effects in a dose-dependent manner. Remimazolam, an ultrashort-acting benzodiazepine, has been approved for procedural sedation but may delay awakening. This study tested the hypothesis that remimazolam as a supplement reduces effect-site propofol concentration (Ceprop) required to suppress response to cervical dilation in patients undergoing hysteroscopy. METHODS: One hundred and fifty patients who were scheduled for hysteroscopy were randomized to receive 0, 0.05, 0.1, 0.15, or 0.2 mg·kg-1 intravenous remimazolam, followed by a bolus of sufentanil 0.15 µg⋅kg-1, and a target-controlled propofol infusion. The initial target Ceprop was 3.5 µg·mL-1 and was increased or decreased in subsequent patients by steps of 0.5 µg·mL-1 according to whether there was loss of response to cervical dilation in the previous patient. We used up-down sequential analysis to determine values of Ceprop that suppressed response to cervical dilation in 50% of patients (EC50). RESULTS: The EC50 of propofol for suppressing response to cervical dilation was lower in patients given 0.1 mg·kg-1 (2.08 [95% confidence interval, CI, 1.88-2.28] µg·mL-1), 0.15 mg⋅kg-1 (1.83 [1.56-2.10] µg·mL-1), and 0.2 mg⋅kg-1 (1.43 [1.27-1.58] µg·mL-1) remimazolam than those given 0 mg⋅kg-1 (3.67 [3.49-3.86] µg·mL-1) or 0.05 mg⋅kg-1 (3.47 [3.28-3.67] µg·mL-1) remimazolam (all were P < .005). Remimazolam at doses of 0.1, 0.15, and 0.2 mg·kg-1 decreased EC50 of propofol by 43.3% (95% CI, 41.3%-45.5%), 50.3% (48.0%-52.8%), and 61.2% (58.7%-63.8%), respectively, from baseline (remimazolam 0 mg⋅kg-1). Propofol consumption was lower in patients given 0.1 mg⋅kg-1 (4.15 [3.51-5.44] mg·kg-1), 0.15 mg⋅kg-1 (3.54 [3.16-4.46] mg·kg-1), and 0.2 mg⋅kg-1 (2.74 [1.73-4.01] mg·kg-1) remimazolam than those given 0 mg⋅kg-1 (6.09 [4.99-7.35] mg·kg-1) remimazolam (all were P < .005). Time to anesthesia emergence did not differ significantly among the 5 groups. CONCLUSIONS: For women undergoing hysteroscopic procedures, remimazolam at doses from 0.1 to 0.2 mg·kg-1 reduced the EC50 of propofol inhibiting response to cervical dilation and the total propofol requirement. Whether the combination could improve perioperative outcomes deserves further investigation.

High tunneling electroresistance in ferroelectric tunnel junctions based on two-dimensional α-In2Se3/MoTe2 van der Waals heterostructures.

Ferroelectric polarization-controlled band alignment can be realized in van der Waals heterostructures (vdWHs), which can be used to create new types of ferroelectric tunnel junctions (FTJs). In this work, we design six probable configurations of two-dimensional vdWHs based on a two-dimensional α-In2Se3 ferroelectric material which has two opposite polarization states P↑ and P↓, and the semiconductor MoTe2. First-principles calculations show robust ferroelectric polarization-controlled switching behavior between the high conductance state in configuration AA-P↓ and the low conductance state in configuration AA-P↑ in the most stable AA stacked vdWHs. Based on this vdWH, a two-dimensional transverse FTJ with AA-P↓ or AA-P↑ as the tunneling barrier and (In0.5Sn0.5)2Se3 monolayers (n-type doped) as electrodes is designed. The tunneling electroresistance ratio of the FTJs at the Fermi level reaches 1.22 × 104% when the tunneling barrier contains two repeating units N = 2 and can be greatly increased by increasing the thickness of the ferroelectric layer. Analysis of the work function, charge redistribution, and local density of states is performed to interpret the above phenomena. The findings suggest the great potential of the AA stacked α-In2Se3/MoTe2 vdWH in the design of high-performance FTJs and application in high-density non-volatile memory devices.

Light-induced pure spin current in carbon hexagonal-connected zigzag graphene nanoribbons via magnetic field modulation.

Pure spin current, exhibiting no Joule heat and self-powered characteristics, has recently attracted intensive attention. Here, through first-principles calculations and symmetry analysis, we propose a new method to generate photoelectric pure spin current in carbon hexagonal connected three zigzag graphene nanoribbons (ZGNRs) via magnetic field modulation. Specifically, a device with centro-symmetry is designed, which consists of three ZGNRs using two carbon hexagons as connectors ('2-C6'). When the edge spin states of the three ZGNRs from left to right are modulated to AFM-AFM-AFM or FM-AFM-FM by magnetic fields, excellent pure spin currents are obtained which are independent of the photon energy and the angle of the linearly polarized light. However, when the edge spin states are FM-FM-FM orderly, the photocurrent is nearly zero and can be neglected. Analysis show that the first two spin magnetic structures own the spatial inversion antisymmetric spin density which is the origin of stable pure spin currents, while the FM-FM-FM structure owns Cs symmetric spin density, leading to the nearly zero photocurrent. Our findings provide a scheme for obtaining pure spin currents by changing the spin states of the graphene nanoribbons via magnetic field modulation, which is of great importance for the design of spintronic devices.

The effect of light-irradiated area on the spin dependent photocurrent in zigzag graphene nanoribbon junctions.

In this work, we study the photogalvanic effect of a zigzag graphene nanoribbon junction with a centro-symmetrical structure which consists of 8 zigzag chains by density functional calculations. Specifically, we focus on the cases where the irradiated region is just part of the central region and located at different positions, with an aim to see how the spin dependent photocurrents will change and whether pure spin current can be obtained. It is found that the magnitude of the spin-dependent photocurrents increases with a gradual increase of the irradiated region and pure spin current is achieved when and only when the entire central region is irradiated. In addition, we studied the additive effect in this device to see that if we divide the central region into two parts, whether the sum of the spin current generated by irradiating the two parts individually is equal to that produced when the entire central region is irradiated. It is found that the sum of the spin currents produced by irradiating the two parts individually is smaller than that obtained by irradiating the whole central region, which means that the rule of "1 + 2 = 3" does not hold and the coupling effect between the two parts is important in photocurrent generation.

Realizing pure spin current by the photogalvanic effect in armchair graphene nanoribbons with nano-constriction engineering.

We propose nano-constriction engineering of armchair graphene nanoribbons (AGNRs) to construct photoelectric nanodevices aiming to generate pure spin currents through the photogalvanic effect (PGE) using first-principles calculations. Two devices with different symmetries were designed, one by introducing only one isosceles zigzag triangle defect on the lower edge of the central region ('D1') and the other by two symmetrically distributed isosceles zigzag triangle defects on the two edges ('D2'). The results show that pure spin current without accompanying charge current can be generated in both junctions, but with a big difference that pure spin current can be generated only at special polarization angles θ = 0°, 90° and 180° in device D1, while it can be generated at any polarization angle in D2. The robustness in D2 is attributed to the spatial inversion symmetry in geometry and the inversion antisymmetry of spin density. These findings suggest that local magnetism engineering provides a reliable method for generating robust pure spin currents with the PGE in nonmagnetic systems, especially opening up new possibilities for the application of AGNRs in spintronics.

Chromosome-level genome assembly of bunching onion illuminates genome evolution and flavor formation in Allium crops.

The Allium genus is cultivated globally as vegetables, condiments, or medicinal plants and is characterized by large genomes and strong pungency. However, the genome evolution and genomic basis underlying their unique flavor formation remain poorly understood. Herein, we report an 11.27-Gb chromosome-scale genome assembly for bunching onion (A. fistulosum). The uneven bursts of long-terminal repeats contribute to diversity in genome constituents, and dispersed duplication events largely account for gene expansion in Allium genomes. The extensive duplication and differentiation of alliinase and lachrymatory factor synthase manifest as important evolutionary events during flavor formation in Allium crops. Furthermore, differential selective preference for flavor-related genes likely lead to the variations in isoalliin content in bunching onions. Moreover, we reveal that China is the origin and domestication center for bunching onions. Our findings provide insights into Allium genome evolution, flavor formation and domestication history and enable future genome-assisted breeding of important traits in these crops.

Clinical effect analysis of laminectomy alone and laminectomy with instrumentation in the treatment of TOLF.

BACKGROUND: To explore the clinical effect of laminectomy alone and laminectomy with instrumentation in the treatment of TOLF. METHODS: A retrospective study was conducted on the clinical data of 142 patients with TOLF and laminectomy who underwent spine surgery at XXX Medical University from January 2003 to January 2018. According to whether the laminectomy was combined with instrumentation, the patients were divided into two groups: group A (laminectomy alone (LA), n = 77) and group B (laminectomy with instrumentation (LI), n = 65). Comparisons of possible influencing factors of demographic variables and operation-related variables were carried out between the two groups. In this study, the clinical effects of LA and LI in the treatment of TOLF were discussed. Thus, we explored the clinical effect of LA and LI in the treatment of TOLF. RESULTS: In terms of demographics, there was a statistically significant difference in BMI between group A and group B (P < 0.05). The differences in age, sex, smoking, drinking, heart disease, hypertension and diabetes were not statistically significant (P > 0.05). In terms of preoperative symptoms, there was a significant difference in gait disturbance, pain in the LE, and urination disorder between group A and group B (P < 0.05), but there was no significant difference in other variables between the two groups (P > 0.05). In terms of operation-related variables, there was a significant difference in the preoperative duration of symptoms, intramedullary signal change on MRI, dural ossification, residual rate of cross-sectional spinal canal area on CT, shape on the sagittal MRI, operation time, pre-mJOA, post-mJOA at 1 year, and leakage of cerebrospinal fluid between group A and group B (P < 0.05), but there was no significant difference in other variables between the two groups (P > 0.05). The preoperative average JOA score of group A was 6.37 and that of group B was 5.19. In group A, the average JOA score at 6 months, 1 year and 2 years after surgery was 7.87, 8.23 and 8.26, respectively, and the average JOA score improvement rate was 32.79 %, 38.32 and 38.53 %, respectively. In group B, the average JOA score at 6 months, 1 year and 2 years after surgery was 7.74, 8.15 and 8.29, respectively, and the average JOA score improvement rate was 39.15 %, 46.86 and 47.12 %, respectively. CONCLUSIONS: Currently, there is no consensus on whether instrumentation is needed after laminectomy for TOLF. We found that for patients with a long duration of gait disturbance, urination disorder, preoperative duration of symptoms, intramedullary signal change on MRI, dural ossification, residual rate of cross-sectional spinal canal area on CT less than 60 %, and shape on the sagittal MRI being beak and low, pre-mJOA had better clinical effects after LI as compared to those after LA, and the incidence of perioperative complications was lower.

Complete remission of refractory pemphigus vulgaris in a Chinese patient with mutated NUDT15 by combination of minimal doses of azathioprine and prednisone.

Although azathioprine (AZA) combined with corticosteroids remains the first-line therapy to treat patients with pemphigus vulgaris (PV), there are increasing reports of AZA-induced leukopenia, which provides the rationale for monitoring the blood cell count and testing the genotypes at the thiopurine methyltransferase (TPMT) and the nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genes. Here, we reported a case of persistent refractory PV in a Chinese patient with three runs of AZA-corticosteroids treatment. In the first two runs he received AZA-corticosteroids at standard or slightly reduced doses and developed leukopenia. In the third run of treatment, he was found to have NUDT15 mutation (rs116855232) and wild-type homozygous TPMT*3C (rs1142345), treatment with minimal doses of AZA and prednisone resulted in a complete remission of PV without any side effects including leukopenia. Our observations not only highlight the benefits of testing the TPMT and NUDT15 genotypes and monitoring the dynamic changes of the white blood cell count in guiding the AZA therapy, but also suggest the potential of using the AZA-corticosteroids combination at very low doses in the treatment of refractory PV.

Improved SERS Performance and Catalytic Activity of Dendritic Au/Ag Bimetallic Nanostructures Based on Ag Dendrites.

Bimetallic nanomaterials, which exhibit a combination of the properties associated with two different metals, have enabled innovative applications in nanoscience and nanotechnology. Here, we introduce the fabrication of dendritic Au/Ag bimetallic nanostructures for surface-enhanced Raman scattering (SERS) and catalytic applications. The dendritic Au/Ag bimetallic nanostructures were prepared by combining the electrochemical deposition and replacement reaction. The formation of Au nanoparticle shell on the surface of Ag dendrites greatly improves the stability of dendritic nanostructures, followed by a significant SERS enhancement. In addition, these dendritic Au/Ag bimetallic nanostructures are extremely efficient in degrading 4-nitrophenol (4-NP) compared with the initial dendritic Ag nanostructures. These experimental results indicate the great potential of the dendritic Au/Ag bimetallic nanostructures for the development of excellent SERS substrate and highly efficient catalysts.

Predictive value of leukocyte telomere length for the severity of coronary artery disease.

Aim: This study aimed to explore leukocyte telomere length (LTL) in the prediction of the severity of coronary artery disease (CAD). Materials & methods: A total of 359 CAD patients who underwent coronary angiography were enrolled in this study. Severity of coronary artery was assessed by Gensini score (GS). Results: LTL is negatively correlated with GS (Spearman's rank correlation coefficient = -0.335; p < 0.001). Multivariate logistic regression results showed that LTL was an independent predictor of high GS (p = 0.001). Area under the curve value of LTL for predicting high GS was 0.659 (p < 0.001). Conclusion: LTL could be considered as a potential predictor of the severity of coronary artery in patients with CAD.

Brassinosteroid-mediated reactive oxygen species are essential for tapetum degradation and pollen fertility in tomato.

Phytohormone brassinosteroids (BRs) are essential for plant growth and development, but the mechanisms of BR-mediated pollen development remain largely unknown. In this study, we show that pollen viability, pollen germination and seed number decreased in the BR-deficient mutant d^im , which has a lesion in the BR biosynthetic gene DWARF (DWF), and in the bzr1 mutant, which is deficient in BR signaling regulator BRASSINAZOLE RESISTANT 1 (BZR1), compared with those in wild-type plants, whereas plants overexpressing DWF or BZR1 exhibited the opposite effects. Loss or gain of function in the DWF or BZR1 genes altered the timing of reactive oxygen species (ROS) production and programmed cell death (PCD) in tapetal cells, resulting in delayed or premature tapetal degeneration, respectively. Further analysis revealed that BZR1 could directly bind to the promoter of RESPIRATORY BURST OXIDASE HOMOLOG 1 (RBOH1), and that RBOH1-mediated ROS promote pollen and seed development by triggering PCD and tapetal cell degradation. In contrast, the suppression of RBOH1 compromised BR signaling-mediated ROS production and pollen development. These findings provide strong evidence that BZR1-dependent ROS production plays a critical role in the BR-mediated regulation of tapetal cell degeneration and pollen development in Solanum lycopersicum (tomato) plants.

A Tunable Dual-Band and Polarization-Insensitive Coherent Perfect Absorber Based on Double-Layers Graphene Hybrid Waveguide.

A suspended monolayer graphene has only about 2.3% absorption rate in visible and infrared band, which limits its optoelectronic applications. To significantly increase graphene's absorption efficiency, a tunable dual-band and polarization-insensitive coherent perfect absorber (CPA) is proposed in the mid-infrared regime, which contains the silicon array coupled in double-layers graphene waveguide. Based on the FDTD methods, dual-band perfect absorption peaks are achieved in 9611 nm and 9924 nm, respectively. Moreover, due to its center symmetric feature, the proposed absorber also demonstrates polarization-insensitive. Meanwhile, the coherent absorption peaks can be all-optically modulated by altering the relative phase between two reverse incident lights. Furthermore, by manipulating the Fermi energies of two graphene layers, two coherent absorption peaks can move over a wide spectrum range, and our designed CPA can also be changed from dual-band CPA to narrowband CPA. Thus, our results can find some potential applications in the field of developing nanophotonic devices with excellent performance working at the mid-infrared regime.

[Establishment and application of a cell model for LRRC8A physiological characteristic study].

The aim of the present study was to establish a cell model of volume-regulated anion channel subunit LRRC8A and investigate the physiological characteristics of LRRC8A. The eukaryotic expression vectors of LRRC8A and YFP-H148Q/I152L were constructed and transfected into Fischer rat thyroid (FRT) cells by Lipofectamine 2000. The FRT cell lines co-expressing LRRC8A and YFP-H148Q/I152L were obtained by antibiotic screening. The expression of LRRC8A and YFP-H148Q/I152L in FRT cells was detected by the inverted fluorescence microscope. The fluorescence quenching kinetic experiment was done to verify the function and effectiveness of the cell model. Then the cell model was utilized to study the physiological characteristics of LRRC8A, such as the characteristics of anion transport, the opening of LRRC8A by osmotic pressure, the effect of anion transport velocity, and the effect of chloride channel inhibitors on LRRC8A anion channel. The results of the inverted fluorescence microscope showed that LRRC8A was expressed on the cell membrane and YFP-H148Q/I152L was expressed in the cytoplasm. The results of fluorescence quenching kinetic test showed that under the condition of low osmotic state, LRRC8A could transport some kinds of anions, such as iodine and chloride ions. Osmotic pressure played a key role in the regulation of LRRC8A volume-regulated anion channel opening. Chloride channel inhibitors inhibited ion transport of LRRC8A channel in a dose-dependent manner. It is suggested that LRRC8A has the characteristics of classic volume-regulated anion channels by using the cell model of FRT cells co-expressing LRRC8A and YFP-H148Q/I152L.

Morphology-Controlled Fabrication of Large-Scale Dendritic Silver Nanostructures for Catalysis and SERS Applications.

Highly branched metallic nanostructures, which possess a large amount of catalyst active sites and surface-enhanced Raman scattering (SERS) hot spots owing to their large surface areas, multi-level branches, corners, and edges, have shown potential in various applications including catalysis and SERS. In this study, well-defined dendritic silver (Ag) nanostructures were prepared by a facile and controllable electrochemical deposition strategy. The morphology of Ag nanostructures is controlled by regulating electrodeposition time and concentration of AgNO3 in the electrolyte solution. Compared to conventional Ag nanoparticle films, dendritic Ag nanostructures exhibited larger SERS enhancement ascribed to the numerous hot spots exist in the nanogaps of parallel and vertically stacked multilayer Ag dendrites. In addition, the prepared dendritic Ag nanostructures show 3.2-fold higher catalytic activity towards the reduction of 4-nitrophenol (4-NP) by NaBH4 than the Ag nanoparticle films. The results indicate that the dendritic Ag nanostructures represent a unique bifunctional nanostructure that serves as both efficient catalysts and excellent SERS substrates, which may be further employed as a nanoreactor for in situ investigation and real-time monitoring of catalytic reactions by SERS technique.

HMGB1 Protects the Heart Against Ischemia-Reperfusion Injury via PI3K/AkT Pathway-Mediated Upregulation of VEGF Expression.

Delivery of exogenous high mobility group box 1 (HMGB1) may exert a beneficial effect on myocardial ischemia-reperfusion (I/R) injury. Since the expression of vascular endothelial growth factor (VEGF) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) in the myocardium mediates the cardioprotective function of basic fibroblast growth factor, we hypothesized that VEGF and the PI3K/Akt signaling pathway also mediate the protective effects of intravenously delivered HMGB1. Thus, the objective of the present study was to analyze the impact of intravenous administration of HMGB1 on the myocardial expression of VEGF, myocardial fibrosis, and cardiac function in rats subjected to acute myocardial I/R. The ischemia was induced by ligation of the left anterior descending coronary artery for 30 min and was followed by 3 h of reperfusion. Myocardial malondialdehyde content, infarct size, and collagen volume fraction decreased, while the activity of superoxide dismutase was increased, the expression of VEGF and p-Akt was upregulated, and cardiac function was improved in the HMGB1-treated group when compared with rats subjected to I/R only (all P < 0.05). However, these effects of HMGB1 were abolished by LY294002. The obtained results demonstrate that the cardioprotective effects of intravenous administration of HMGB1 prior to I/R may be mediated by upregulation of myocardial expression of VEGF, which may activate the PI3K/Akt signaling pathway.

BZR1 Mediates Brassinosteroid-Induced Autophagy and Nitrogen Starvation in Tomato.

Autophagy, an innate cellular destructive mechanism, plays crucial roles in plant development and responses to stress. Autophagy is known to be stimulated or suppressed by multiple molecular processes, but the role of phytohormone signaling in autophagy is unclear. Here, we demonstrate that the transcripts of autophagy-related genes (ATGs) and the formation of autophagosomes are triggered by enhanced levels of brassinosteroid (BR). Furthermore, the BR-activated transcription factor brassinazole-resistant1 (BZR1), a positive regulator of the BR signaling pathway, is involved in BR-induced autophagy. Treatment with BR enhanced the formation of autophagosomes and the transcripts of ATGs in BZR1-overexpressing plants, while the effects of BR were compromised in BZR1-silenced plants. Yeast one-hybrid analysis and chromatin immunoprecipitation coupled with quantitative polymerase chain reaction revealed that BZR1 bound to the promoters of ATG2 and ATG6 The BR-induced formation of autophagosomes decreased in ATG2- and ATG6-silenced plants. Moreover, exogenous application of BR enhanced chlorophyll content and autophagosome formation and decreased the accumulation of ubiquitinated proteins under nitrogen starvation. Leaf chlorosis and chlorophyll degradation were exacerbated in BZR1-silenced plants and the BR biosynthetic mutant d^im but were alleviated in BZR1- and BZR1-1D-overexpressing plants under nitrogen starvation. Meanwhile, nitrogen starvation-induced expression of ATGs and autophagosome formation were compromised in both BZR1-silenced and d^im plants but were increased in BZR1- and BZR1-1D-overexpressing plants. Taken together, our results suggest that BZR1-dependent BR signaling up-regulates the expression of ATGs and autophagosome formation, which plays a critical role in the plant response to nitrogen starvation in tomato (Solanum lycopersicum).

S897 phosphorylation of EphA2 is indispensable for EphA2-dependent nasopharyngeal carcinoma cell invasion, metastasis and stem properties.

Our phosphoproteomics identified that phosphorylation of EphA2 at serine 897 (pS897-EphA2) was significantly upregulated in the high metastatic nasopharyngeal carcinoma (NPC) cells relative to non-metastatic NPC cells. However, the role and underlying mechanism of pS897-EphA2 in cancer metastasis and stem properties maintenance remain poorly understood. In this study, we established NPC cell lines with stable expression of exogenous EphA2 and EphA2-S897A using endogenous EphA2 knockdown cells, and observed that pS897-EphA2 maintained EphA2-dependent NPC cell in vitro migration and invasion, in vivo metastasis and cancer stem properties. Using phospho-kinase antibody array to identify signaling downstream of pS897-EphA2, we found that AKT/Stat3 signaling mediated pS897-EphA2-promoting NPC cell invasion, metastasis and stem properties, and Sox-2 and c-Myc were the effectors of pS897-EphA2. Immunohistochemistry showed that pS897-EphA2 was positively correlated with NPC metastasis and negatively correlated with patient overall survival. Moreover, ERK/RSK signaling controlled serum-induced pS897-EphA2 in NPC cells. Collectively, our results demonstrate that pS897-EphA2 is indispensable for EphA2-dependent NPC cell invasion, metastasis and stem properties by activating AKT/Stat3/Sox-2 and c-Myc signaling pathway, suggesting that pS897-EphA2 can serve as a therapeutic target in NPC and perhaps in other cancers.

[Methylation Analysis and Validation of Whole Genome DNA in Active Tuberculosis].

OBJECTIVE: To screen and identify the gene of DNA methylation in patients with active tuberculosis. METHODS: ① This study enrolled 9 cases of active tuberculosis patients (including 3 newly diagnosed tuberculosis patients and 6 cases of retreatment of active tuberculosis patients), 3 cases of latent tuberculosis patients and 3 cases of healthy controls. Genome DNA was extracted from Peripheral Blood Mononuclear Cell and following bisulfite conversion treatment. After hybridization with the Illumina HD 450K Infinium Mehtylation BeadChip, the results were compared between patients group and control group, GO and Pathway analysis were performed to evaluate the function of differentially expressed genes; ② We further enrolled 60 cases of active tuberculosis patients and 60 cases of health controls (their age and gender were matched). By using pyrosequencing method to detect the methylation levels of candidate genes (TLR1, TLR2, TLR4) screened by gene chip. RESULTS: ① Compared with healthy controls, we found that most of them were showed demethylation status. GO and Pathway analysis showed that the functions of the differentially methylated regions related genes were mainly enriched in the biological processes of the regulation of leukocyte apoptosis, cytokine regulation and inflammatory response which were closely related to tuberculosis. ②There were 10 CpG sites involved in the verified tuberculosis related genes (TLR1, TLR2, TLR4), the CpG sites of TLR1 gene showed the hypermethylation status (P<0.001), the CpG sites of TLR4 gene showed demethylation status (P=0.012). CONCLUSION: The present study demonstrated that in the course of MTB infection, the methylation status of genomic DNA was altered, and most of the Differentially Methylated Regions (DMRs) were showed status of demethylation. TLR1 gene and TLR4 gene may play an important role in the occurrence and development of tuberculosis.

ADRB3 Gene Trp64Arg Polymorphism and Essential Hypertension: A Meta-Analysis Including 9,555 Subjects.

Background: Presence of the ß3-Adrenergic receptor (ADRB3) gene Trp64Arg (T64A) polymorphism may be associated with an increased susceptibility for essential hypertension (EH). A clear consensus, however, has yet to be reached. Objective and methods: To further elucidate the relationship between the ADRB3 gene Trp64Arg polymorphism and EH, a meta-analysis of 9,555 subjects aggregated from 16 individual studies was performed. The combined odds ratios (ORs) and their corresponding 95% confidence intervals (CI) were evaluated using either a random or fixed effect model. Results: We found a marginally significant association between ADRB3 gene Trp64Arg polymorphism and EH in the whole population under the additive genetic model (OR: 1.200, 95% CI: 1.00-1.43, P = 0.049). Association within the Chinese subgroup, however, was significant under allelic (OR: 1.150, 95% CI: 1.002-1.320, P = 0.046), dominant (OR: 1.213, 95% CI: 1.005-1.464, P = 0.044), heterozygous (OR: 1.430, 95% CI:1.040-1.970, P = 0.03), and additive genetic models (OR: 1.280, 95% CI: 1.030-1.580, P = 0.02). A significant association was also found in the Caucasian subgroup under allelic (OR: 1.850, 95% CI: 1. 260-2.720, P = 0.002), dominant (OR: 2.004, 95% CI: 1.316-3.052, P = 0.001), heterozygous (OR: 2.220, 95% CI: 1.450-3.400, P = 0.0002), and additive genetic models (OR: 2.000, 95% CI: 1. 330-3.010, P = 0.0009). Conclusions: The presence of the ADRB3 gene Trp64Arg polymorphism is positively associated with EH, especially in the Chinese and Caucasian population. The Arg allele carriers of ADRB3 gene Trp64Arg polymorphism may be at an increased risk for developing EH.