Cardiovascular Risk in Patients With Treated Isolated Diastolic Hypertension and Isolated Low Diastolic Blood Pressure.

BACKGROUND: The prognosis of high or markedly low diastolic blood pressure (DBP) with normalized on-treatment systolic blood pressure on major adverse cardiovascular events (MACEs) is uncertain. This study examined whether treated isolated diastolic hypertension (IDH) and treated isolated low DBP (ILDBP) were associated with MACEs in patients with hypertension. METHODS AND RESULTS: A total of 7582 patients with on-treatment systolic blood pressure <130 mm Hg from SPRINT (Systolic Blood Pressure Intervention Trial) were categorized on the basis of average DBP: <60 mm Hg (n=1031; treated ILDBP), 60 to 79 mm Hg (n=5432), ≥80 mm Hg (n=1119; treated IDH). MACE risk was estimated using Cox proportional-hazards models. Among the SPRINT participants, median age was 67.0 years and 64.9% were men. Over a median follow-up of 3.4 years, 512 patients developed a MACE. The incidence of MACEs was 3.9 cases per 100 person-years for treated ILDBP, 1.9 cases for DBP 60 to 79 mm Hg, and 1.8 cases for treated IDH. Comparing with DBP 60 to 79 mm Hg, treated ILDBP was associated with an 1.32-fold MACE risk (hazard ratio [HR], 1.32, 95% CI, 1.05-1.66), whereas treated IDH was not (HR, 1.18 [95% CI, 0.87-1.59]). There was no effect modification by age, sex, atherosclerotic cardiovascular disease risk, or cardiovascular disease history (all P values for interaction >0.05). CONCLUSIONS: In this secondary analysis of SPRINT, among treated patients with normalized systolic blood pressure, excessively low DBP was associated with an increased MACE risk, while treated IDH was not. Further research is required for treated ILDBP management.

Optimal stroke preventive strategy for patients aged 80 years or older with atrial fibrillation: a systematic review with traditional and network meta-analysis.

BACKGROUND: An optimal antithrombotic strategy for patients aged 80 years or older with atrial fibrillation (AF) remains elusive. OBJECTIVE: Using a systematic review with traditional and network meta-analysis, we investigated outcomes in AF patients ≥80 years treated with different antithrombotic strategies. METHODS: We searched eligible randomised controlled trials (RCTs) and observational studies from MEDLINE, EMBASE, Cochrane Library and Web of Science databases from inception to 16 December 2021. Research comparing treatment outcomes of novel oral anticoagulants (NOACs), aspirin, vitamin K antagonists (VKAs) or no oral anticoagulant/placebo therapy in patients ≥80 years with AF were included. Outcomes were stroke or systemic embolism (SSE), major bleeding, all-cause mortality, intracranial bleeding (ICH) and gastrointestinal bleeding. Traditional and network meta-analyses were performed. Net clinical benefit integrating SSE and major bleeding was calculated. RESULTS: Fifty-three studies were identified for analysis. In the meta-analysis of RCTs, risk of SSE (risk ratio [RR]: 0.82; 95% confidence interval [CI]: 0.73-0.99) and ICH (RR: 0.38; 95% CI: 0.28-0.52) was significantly reduced when NOACs were compared with VKAs. Network meta-analysis of RCTs demonstrated that edoxaban (P-score: 0.8976) and apixaban (P-score: 0.8528) outperformed other antithrombotic therapies by showing a lower major bleeding risk and better net clinical benefit. Both traditional and network meta-analyses from RCTs combining with observational studies showed consistent results. CONCLUSIONS: In patients aged 80 years or older with AF, NOACs have better outcomes than VKAs regarding efficacy and safety profiles. Edoxaban and apixaban may be preferred treatment options since they are safer than other antithrombotic strategies.

Nanocomposites of graphene and zirconia for adsorption of organic-arsenic drugs: Performances comparison and analysis of adsorption behavior.

3-Nitro-4-hydroxy-phenylarsonic acid (3-NHPAA), an organic-arsenic compound, as one of widely used antibacterial veterinary drug, has greatly attracted the attention due to its potential threats on ecological environment. A series of the nanocomposites of zirconia nanoparticles with crystal phases (pure monoclinic, pure tetragonal and mixed phase (monoclinic + tetragonal)) anchored on reduced graphene oxide were produced through managing the concentration of triethanolamine solution and the reaction time. The effects of the crystal phases of the zirconia in the structure of the nanocomposites were played a key role in the adsorption performances of the 3-NHPAA. Experiment data identified the nanocomposites with monoclinic phase of zirconia excelled at the adsorption of the 3-NHPAA with a higher adsorption capacity up to 207.2 mg g-1. The uptake of the 3-NHPAA by the three nanocomposites was implemented within 60 min and highly pH-dependent which illustrated electrostatic attraction between them as a main mechanism during the adsorption process. A wider pH range (3.8-8.8) for the uptake of the 3-NHPAA by the nanocomposites with the monoclinic phase of zirconia was obtained compared with the nanocomposites containing tetragonal phase (3.8-5.9) or the mixed phase (3.8-7.1) of zirconia. The adsorption of the 3-NHPAA was well described by the pseudo-second order kinetic and Langmuir equations. The thermodynamic parameters suggested that the adsorption of the 3-NHPAA over the three nanocomposites was endothermic and spontaneous in nature. In summary, the nanocomposites of reduced graphene oxide and monoclinic phase of zirconia nanoparticles as an adsorbent were better to the adsorption of the 3-NHPAA.

Mechanistic target of rapamycin-mediated autophagy is involved in the alleviation of lipopolysaccharide-induced acute lung injury in rats.

Acute lung injury (ALI) is a complex clinical syndrome with high morbidity and mortality rates. Autophagy is an adaptive process that plays a complex role in ALI. The aim of this study was to investigate the effects of autophagy on lipopolysaccharide (LPS)-induced lung injury by establishing a rat ALI model and to further explore the possible mechanisms involved. Rats were pretreated with the autophagy inhibitor 3-methyladenine (3-MA) or the autophagy activator rapamycin before they were challenged with the intratracheal instillation of LPS (5 mg/kg). The level of autophagy in the lung tissue was detected. Lung injury and vascular permeability were assessed. The role of the mechanistic target of rapamycin (mTOR)-mediated Unc-51-like kinase 1 (ULK1) and the class III PI3 kinase VPS34 in autophagy regulation was examined. LPS challenge induced autophagy and rapamycin pretreatment enhanced autophagy activity in LPS-induced ALI rats. LPS caused severe lung injury and high pulmonary vascular permeability, which could be alleviated by enhancing autophagy. In addition, the inhibition of mTOR upregulated the expression of ULK1 and VPS34 and thus increased LPS-induced autophagy. Autophagy plays a protective role in LPS-induced ALI, and enhancing autophagy via the inhibition of mTOR alleviates lung injury and pulmonary barrier function. Moreover, mTOR negatively mediates ULK1 and VPS34 to regulate LPS-induced autophagy in rats.

A highly conjugated benzimidazole carbene-based ruthenium sensitizer for dye-sensitized solar cells.

A new type of carbene-based ruthenium sensitizer, CB104, with a highly conjugated ancillary ligand, diphenylvinylthiophene-substituted benzimidazolepyridine, was designed and developed for dye-sensitized solar cell applications. The influence of the thiophene antenna on the performance of the cell anchored with CB104 was investigated. Compared with the dye CBTR, the conjugated thiophene in the ancillary ligand of CB104 enhanced the molar extinction coefficient of the intraligand π-π* transition and the intensity of the lower energy metal-to-ligand charge-transfer band. However, the incident photon-to-current conversion efficiency spectrum of the cell anchored with CB104 (0.15 mM) showed a maximum of 63 % at 420 nm. The cell sensitized with the dye CB104 attained a power conversion efficiency of 7.30 %, which was lower than that of the cell with nonconjugated sensitizer CBTR (8.92 %) under the same fabrication conditions. The variation in the performance of these two dyes demonstrated that elongating the conjugated light-harvesting antenna resulted in the reduction of short-circuit photocurrent density, which might have been due to the aggregation of dye molecules. In the presence of a coabsorbate, chenodeoxycholic acid, the CB104-sensitized cell exhibited an enhanced photocurrent density and achieved a photovoltaic efficiency of 8.36 %.

[Effect of electroacupuncture of "Fenglong" (ST 40) on levels of blood lipid and macrophage TNF-alpha and IL-6 in hyperlipidemic rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Fenglong" (ST 40) on blood lipid contents and inflammatory factor levels in hyperlipemia rats so as to elucidate its mechanism underlying improvement of hyperlipemia. METHODS: Fifty male SD rats were randomized into 5 groups: normal, model, diet -control, EA intervention (EA), diet-control + EA groups, with 10 rats in each group. Hyperlipemia model was established by feeding the animals with high-fat diet for 30 days. After modeling, rats in the diet-control group were fed with routine fodder. EA was applied to bilateral "Fenglong" (ST 40) for 30 min, once daily for 30 days. Following intraperitoneal injection of 1640 culture fluid, the peritoneal fluid was collected and centrifuged for extracting macrophages. Flow cytometry (FCM) was employed to determine the levels of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) after adding fluoresce-labeled antibodies. RESULTS: The contents of serum TC and LDL-C were remarkably higher and HDL-C level was significantly lower in the model group than in the normal group (P < 0.01). After EA intervention, serum TC and LDL-C showed an apparent decrease (P < 0.01). Compared with the normal group, percentages of CD11 b, TNF-alpha and IL-6 were significantly increased in the model group (P < 0.01), while in comparison with the model group, percentages of CD11 b in both EA and diet-control + EA groups, TNF-alpha and IL-6 percentages of macrophages in the diet-control, EA and diet-control + EA groups were notably decreased (P < 0.05, P < 0.01). The effects of the diet-control + EA group were considerably superior to those of the diet-control group in lowering CD11 b, TNF-alpha and IL-6 percentages (P < 0.05, P < 0.01). No significant differences were found between the diet-control and EA groups in the aforementioned indexes (P > 0.05). CD11 b level indicates changes of macrophage level due to its specific marker character. CONCLUSION: EA stimulation of "Fenglong" (ST 40) is effective in lowering serum TC, LDL-C, and macrophage TNF-alpha and IL-6 levels in hyperlipemia rats.

Analysis of global methylation using a Zta-expressing nasopharyngeal carcinoma cell line.

EBV infects more than 90% of the human population and persists in most individuals as a latent infection where the viral genome is silenced by host-driven methylation. The lytic cycle is initiated when the viral protein Zta binds to methylated BRLF1 and BRRF1 promoters. Although studies reveal the role of Zta and methylation changes in the viral genome upon EBV infection to reactivation, whether Zta plays any role in alteration of methylation in the host genome remains unknown. Using an inducible model, we demonstrate that global DNA methylation, based on whole-genome 5-methylcytosine content, and regional DNA methylation in repetitive elements, imprinting genes and the X chromosome, remains unchanged in response to Zta expression. Expression of DNA methyltransferases was also unaffected by ectopically expressed Zta. Our data imply that alteration of host gene expression following EBV reactivation may reflect methylation-independent Zta-mediated gene activation and not epigenetic modification of the host genome.

Computational analysis and refinement of sequence structure on chromosome 22q11.2 region: application to the development of quantitative real-time PCR assay for clinical diagnosis.

The low-copy repeat (LCR) is a new class of repetitive DNA element and has been implicated in many human disorders, including DiGeorge/velocardiofacial syndrome (DGS/VCFS). It is now recognized that nonallelic homologous recombination (NAHR) through LCRs flanking the chromosome 22q11.2 region leads to genome rearrangements and results in the DGS/VCFS. To refine the structure and content of chromosome 22q11.2 LCRs, we applied computational analysis to dissect region-specific LCRs using publicly available sequences. Nine distinct duplicons between 1.6 and 65 kb long and sharing >95% sequence identity were identified. The presence of these sequence motifs supports the NAHR mechanism. Further sequence analysis suggested that the previously defined 3-Mb deletion may actually comprise two deletion intervals of similar size close to each other and thus indistinguishable when using fluorescence in situ hybridization (FISH) analysis. The differentially deleted regions contain several hypothetical proteins and UniGene clusters and may partially explain the clinical heterogeneity observed in DGS/VCFS patients with the 3-Mb common deletion. To implement further sequence information in molecular medicine, we designed a real-time quantitative PCR assay and validated the method in 122 patients with suspected DGS/VCFS. The assay detected 28 patients with chromosome 22q11.2 deletion later confirmed using FISH. Our results indicated that the developed assay is reliable as well as time and cost effective for clinical diagnosis of chromosome 22q11.2 deletion. They also suggest that this methodology can be applied to develop a molecular approach for clinical detection and diagnosis of other genomic disorders.