Graphene Oxide Nanoparticles Combined with CRISPR/Cas9 System Enable Efficient Inhibition of Pseudorabies Virus.

We describe an application where graphene oxide nanoparticles (GONs) enable combined inhibition of Pseudorabies Virus (PRV) through delivery of a CRISPR/Cas9 system for targeted cleaving of a PRV genome and direct interaction with viral particles. The sheeted GONs could load CRISPR plasmid DNA (pDNA) to form a small sized, near-spheroidal GONs-CRISPR complex, which enables CRISPR pDNA efficient intracellular delivery and transient expression under serum conditions. Cell studies showed that GONs-CRISPR could allow rapid cellular uptake, endolysosomes escape, and nucleus transport within 3 h. Virus studies demonstrated that the pure GONs have antiviral activity and GONs-CRISPR could significantly inhibit PRV replication and result in progeny PRV decreasing by approximately 4000 times in infected host cells. Transmission electron microscopy (TEM) imaging showed that GONs-CRISPR could destroy the PRV structures by directly interacting with viral particles. This GONs-based strategy may extend the advanced application of the CRISPR system for antiviral action.

Intake of Diacylglycerols and the Fasting Insulin and Glucose Concentrations: A Meta-Analysis of 5 Randomized Controlled Studies.

Diacylglycerol (DAG) supplementation has been shown to be associated with the health improvement of patients with diabetes mellitus, although this efficacy is uncertain. We quantitatively examined the effect of dietary DAG on fasting serum glucose and insulin concentrations by conducting a meta-analysis of randomized controlled trials. Potential papers were initially searched from electronic databases of Medline, Embase, and Cochrane Library. Inclusion criteria required the trial to be randomized, with triacylglycerol (TAG) controlled with fasting serum glucose or insulin concentration as one of the end points. Information was extracted independently by two reviewers and the effect of DAG was examined using Review Manager 4.2. Results showed that DAG reduced fasting serum insulin concentration significantly compared with TAG (weighted mean difference [WMD] = -8.23 pmol/l; 95% confidence interval [CI], -15.17 to -1.28 pmol/l; p = 0.02). In addition, DAG supplementation reduced fasting serum glucose concentration greatly (WMD = -0.10 mmol/l; 95% CI, -0.24 to 0.04 mmol/l; p = 0.18), and this effect was significantly correlated with the duration of intervention (fasting serum glucose concentration = 1.075-0.012; duration of intervention; p = 0.04; r = 0.90). In conclusion, DAG supplementation improved fasting serum glucose and insulin concentrations compared with TAG, and the effect on glucose was significantly correlated with the duration of intervention.

A single-center retrospective study on epidemiological and Traditional Chinese Medicine syndrome characteristics of 21010 patients with reflux/heartburn symptoms.

OBJECTIVE: To provide a basis for the clinical identification of true and false reflux, integrated traditional Chinese and Western medicine, and psychosomatic treatment, we conducted a retrospective study of the etiology and epidemiological and Traditional Chinese Medicine (TCM) syndrome characteristics of patients with reflux/heartburn symptoms. METHODS: The 210 10 patients with reflux/heartburn treated at Tianjin Nankai Hospital from January 1, 2016, to December 31, 2019, were divided into four groups according to their pathogenesis. Sex, age, course of disease, incidence rate, gastroscopy, 24-h pH-impedance, esophageal manometry, Hamilton Anxiety Scale (HAMA) / Hamilton Depression Scale (HAMD) score, 8-week proton pump inhibitor (PPI) treatment effect, and TCM syndrome characteristics were statistically analyzed. RESULTS: A total of 21010 patients (8864 men and 12146 women), with reflux/heartburn symptoms were screened, including 6284 (29.9%) patients with reflux esophagitis (RE), 10427 (49.6%) patients with non-erosive reflux esophagitis (NERD), 2430 (11.6%) patients with reflux hypersensitivity (RH), and 1870 (8.9%) patients with functional heartburn (FH). The incidence of the disease was higher in women than in men (0.0001). The ranking of the incidence of anxiety and depression in these four groups was FH>RH>NERD>RE ( 0.0001). There were more women than men in the groups with anxiety and more men than women in the groups with depression ( 0.0001), and there was no significant difference in the distribution of anxiety and depression between men and women ( 0.5689). There were significant differences in TCM syndrome characteristics between NERD, RE, and functional esophageal diseases ( 0.01). The highest proportion of functional esophageal disease TCM symptoms was stagnation and phlegm obstruction syndrome (36.16%), and there was no significant difference between RH and FH. The effective rates of PPI treatment at 8 weeks in patients in the RE, NERD, RH, and FH groups were 89%, 72%, 54%, and 0%, respectively. RE was classified into grades A, B, C, and D according to the Los Angeles grading system. The ranking of the incidence of these four grades was A>B>C>D ( 0.0001). The effective rates of PPI treatment at 8 weeks were 91%, 81%, 69%, and 63% in patients with grade A, B, C, and D RE, respectively ( 0.0001). The highest proportion of TCM syndrome types of NERD and RE was the stagnated heat syndrome in the liver and stomach syndrome, 38.99% and 33.90%, respectively. CONCLUSION: Reflux/heartburn symptoms are relatively common in middle-aged women, and NERD is the most common etiology, followed by RE, RH, and FH. The most common TCM syndrome characteristics in NERD and RE were stagnated heat syndrome in the liver and stomach syndrome, and stagnation and phlegm obstruction syndrome in functional esophageal diseases. Most patients with reflux/heartburn symptoms also experienced anxiety and depression.

Adaptive amino acid substitutions enable transmission of an H9N2 avian influenza virus in guinea pigs.

H9N2 is the most prevalent low pathogenic avian influenza virus (LPAIV) in domestic poultry in the world. Two distinct H9N2 poultry lineages, G1-like (A/quail/Hong Kong/G1/97) and Y280-like (A/Duck/Hong Kong/Y280/1997) viruses, are usually associated with binding affinity for both α 2,3 and α 2,6 sialic acid receptors (avian and human receptors), raising concern whether these viruses possess pandemic potential. To explore the impact of mouse adaptation on the transmissibility of a Y280-like virus A/Chicken/Hubei/214/2017(H9N2) (abbreviated as WT), we performed serial lung-to-lung passages of the WT virus in mice. The mouse-adapted variant (MA) exhibited enhanced pathogenicity and advantaged transmissibility after passaging in mice. Sequence analysis of the complete genomes of the MA virus revealed a total of 16 amino acid substitutions. These mutations distributed across 7 segments including PB2, PB1, PA, NP, HA, NA and NS1 genes. Furthermore, we generated a panel of recombinant or mutant H9N2 viruses using reverse genetics technology and confirmed that the PB2 gene governing the increased pathogenicity and transmissibility. The combinations of 340 K and 588 V in PB2 were important in determining the altered features. Our findings elucidate the specific mutations in PB2 contribute to the phenotype differences and emphasize the importance of monitoring the identified amino acid substitutions due to their potential threat to human health.

Coexistence of P190 and P210 BCR/ABL transcripts in chronic myeloid leukemia blast crisis resistant to imatinib.

INTRODUCTION: Philadelphia chromosome (Ph) is a hallmark of chronic myeloid leukemia (CML), which exists in more than 90% CML and in 3% to 40% acute lymphoblastic leukemia (ALL). CASE DESCRIPTION: A 25-year-old man was diagnosed with CML in chronic phase. He first received treatment with hydroxyurea, achieving hematological remission and following imatinib mesylate for main treatment. A year later, he began to appear unexplained high fever with ineffective antibiotic treatment and bone morrow and blood tests indicated blast crisis. Both BCR/ABL 210 and BCR/ABL 190 fusion transcript were positive. Imatinib resistance was confirmed by a screening for ABL kinase domain E255K mutations, and dasatinib was administered. After two months, the patient went on to hematological remission. DISCUSSION AND EVALUATION: During medical treatment for CML, we experienced a relatively rare case with co-expression of the p210 and p190 encoding BCR-ABL transcripts in blastic phase. Imatinib resistance was confirmed and remission wasn't easily obtained, yet dasatinib was helpful. When resistance emerges, the treatment options include increasing the daily dose of imatinib, or combining imatinib with other agents. Of course, dasatinib, nilotinib and bone marrow transplantation are good choice as well. CONCLUSIONS: The presence of p-190 transcript in CML may be related to progression of the disease. Thus monitoring the resistance of imatinib in CML patients, especially for advanced phase CML and BCR-ABL ALL, may be meaningful to guide clinical treatment and predict the prognosis.