Adverse events of direct factor Xa inhibitors: a disproportionality analysis of the FAERS database.

OBJECTIVES: Direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, commonly used direct oral anticoagulant (DOAC), are widely used to prevent and treat stroke and venous thromboembolic events in patients with atrial fibrillation (AF). This study aimed to assess and compare reports of adverse events associated with rivaroxaban, apixaban, and edoxaban, including hemorrhagic and non-hemorrhagic events. METHODS: Reporting odds ratio (ROR), proportional reporting ratio (PRR), Medications and Health Care Products Regulatory Agency (MHRA), and the information component (IC) were used to perform a risk assessment of adverse event reports in the FDA Adverse Event Reporting System (FAERS) database for the years 2018-2022. RESULTS: Combined with disproportionality analysis in different backgrounds, the salient risks of the three-factor Xa inhibitors varied. Rivaroxaban had the most significant risk of hemorrhage, apixaban had a higher incidence and risk of death, cardiac and cerebral adverse events, and edoxaban showed a more prominent risk in the kidneys and urinary system. CONCLUSION: Hemorrhage is a common risk with factor Xa inhibitors, with rivaroxaban being the most significant. Apixaban and edoxaban also showed significant association with non-hemorrhagic adverse events, and increased attention to non-hemorrhagic adverse events is needed in clinical use.

Notes on the genus Paracyriothasastes Breuning, 1978 (Coleoptera: Cerambycidae: Lamiinae: Lamiini).

The monotypic genus Paracyriothasastes Breuning, 1978 was established for Cereopsius marmoreus Pascoe, 1857 from Malaysia. Uraechoides Breuning, 1981 was established for Uraechoides vivesi Breuning, 1981 also from Malaysia, and is currently composed of the type species and U. taomeiae Hayashi, Nara Yu, 1995, the latter from China (Taiwan) (Tavakilian Chevillotte 2020).

Aberrant expression of miR-127, miR-21 and miR-16 in placentas of deceased cloned sheep.

Placental deficiencies are associated with developmental abnormalities of animal produced by somatic cell nuclear transfer (SCNT). It is reported that aberrant expression of microRNAs (miRNAs) in the common placenta is associated with fetal growth restriction and placental deficiencies. However, an understanding of the expression and function of miRNAs in the placentas of cloned animal is lacking. In this study, we characterized the expression of five growth-associated miRNAs (miR-127, miR-16, miR-21, miR-93 and miR-182) in placentas of deceased transgenic cloned sheep (deceased group, n=7), live transgenic cloned sheep (live group, n=5) and conventionally produced sheep (control group, n=10). Expression levels of miR-127 (P<0.01), miR-21 (P<0.01) and miR-16 (P<0.05) were significantly up-regulated in the placentas of deceased group compared to that of control group. In contrast, the expression of these miRNAs was largely normal in the placentas of live group, except for the expression of miR-21. Furthermore, we confirmed that retrotransposon-like gene (Rtl1), a key gene in placental development, was down-regulated by miR-127 as a target in placenta cells. Our results suggested that the abnormal expression of miR-127, miR-21 and miR-16 in placentas of deceased sheep, through dysregulation of target genes, may result in developmental deficiencies of transgenic cloned sheep.

Targeted Editing of Myostatin Gene in Sheep by Transcription Activator-like Effector Nucleases.

Myostatin (MSTN) is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Gene knockout of MSTN can result in increasing muscle mass in sheep. The objectives were to investigate whether myostatin gene can be edited in sheep by transcription activator-like effector nucleases (TALENs) in tandem with single-stranded DNA oligonucleotides (ssODNs). We designed a pair of TALENs to target a highly conserved sequence in the coding region of the sheep MSTN gene. The activity of the TALENs was verified by using luciferase single-strand annealing reporter assay in HEK 293T cell line. Co-transfection of TALENs and ssODNs oligonucleotides induced precise gene editing of myostatin gene in sheep primary fibroblasts. MSTN gene-edited cells were successfully used as nuclear donors for generating cloned embryos. TALENs combined with ssDNA oligonucleotides provide a useful approach for precise gene modification in livestock animals.

Development of sheep kidney cells with increased resistance to different subgenotypes of BVDV-1 by RNA interference.

Bovine viral diarrhea virus (BVDV) should be a ubiquitous viral pathogen to the cattle and sheep industry. This pathogen is responsible for severe economic losses. We previously showed that plasmid-mediated dual short hairpin RNA (shRNA) efficiently inhibit BVDV replication in bovine kidney epithelial (MDBK) cells. In this study, we delivered the dual shRNA system to sheep fibroblasts and generated transgenic cell colonies. These transgenic fibroblasts were further used for somatic cell nuclear transfer (SCNT). Three lambs were born at full term, but perished soon after birth. Integration of shRNA into the genome of cloned sheep was confirmed by PCR and expression of shRNA in transgenic sheep was confirmed by real-time PCR. Kidney epithelial cells were isolated from transgenic sheep and challenged with multiple BVDV subgenotypes (BVDV-1a, BVDV-1b and BVDV-1c). The dual shRNA expressed in transgenic kidney epithelial cells significantly inhibited BVDV replication in a cross-resistance manner. Our results showed that transgenic RNAi might be a useful tool for preparation of transgenic animals with increased resistance to BVDV.

Hepatitis B knowledge and preventive practices of Chinese American immigrants in Southern California.

PURPOSE: Chinese American immigrants have higher rates of chronic hepatitis B virus (HBV) infections and consequently higher rates of liver cancer compared to the general U.S. POPULATION: The need to assess this vulnerable population's knowledge and health practices is important to prevent HBV infections and improve outcomes. The purpose of this study was to describe HBV knowledge and preventive practices among Chinese American immigrants in Southern California. DATA SOURCES: Convenience sample of 179 Chinese American immigrants age ≥18 years from Los Angeles County (CA) participated in the study by completing a modified version of the B Free CEED's Hepatitis B Needs Assessment survey. CONCLUSIONS: Most participants were knowledgeable of HBV (91.6%) or HBV vaccination (70.5%), yet screening and vaccination for the virus were low (36.9% and 26.3%, respectively). Low knowledge was also found regarding modes of disease transmission. Barriers to engage preventive practices included: "feeling well/no health problems" and "not suggested by a doctor." These findings suggest the need for further education. IMPLICATIONS FOR PRACTICE: Nurse practitioners can play a significant role in assessing risk and implementing programs that are community focused, culturally sensitive, and evidence based to improve knowledge, screening, and preventive behaviors on HBV infections for this vulnerable population.

Efficient gene knockout in goats using CRISPR/Cas9 system.

The CRISPR/Cas9 system has been adapted as an efficient genome editing tool in laboratory animals such as mice, rats, zebrafish and pigs. Here, we report that CRISPR/Cas9 mediated approach can efficiently induce monoallelic and biallelic gene knockout in goat primary fibroblasts. Four genes were disrupted simultaneously in goat fibroblasts by CRISPR/Cas9-mediated genome editing. The single-gene knockout fibroblasts were successfully used for somatic cell nuclear transfer (SCNT) and resulted in live-born goats harboring biallelic mutations. The CRISPR/Cas9 system represents a highly effective and facile platform for targeted editing of large animal genomes, which can be broadly applied to both biomedical and agricultural applications.

[Influence of Ginkgo biloba extract on proliferation of ACC-2 cell, Survivin and TIP30 gene expression in adenoid cystic carcinoma of lacrimal gland].

Exploring the influence of extract of Ginkgo biloba (EGB) on the proliferation, apoptosis of ACC-2 cell in lacrimal adenoid cystic carcinoma and analyzing the influence of EGB on the gene expression of Survivin and TIP30 based on the levels of the gene and protein. ACC-2 cell in human with ACC of lacrimal gland disposed by EGB of different concentration was in vitro cultured. MTT method was used for cell proliferation detection. Annexin V/PI double-staining flow cytometer was used to detect cell apoptosis and cell cycle. Survivin and TIP30 gene expression together with protein expression were analyzed by RT-PCR and Western blotting. And it is indicated that EGB has inhibitory effect on the proliferation of ACC-2 cell in vitro. Furthermore, the dose-effect relationship was significant. Compared with the control group, it had statistical difference (P <0.01). The inhibitory concentration 50% (ICso) is 88 mg . L-1. By flow cytometer examination, it was indicated that EGB can gradually increase ACC-2 cell in G0-G1 stage and decrease it in G2-M and S stage. With the increase of dose, the apoptosis rate of ACC-2 cell obviously increased (P <0.05 or P <0.01). Both of the expression results of RT-PCR and Western hybrid proteins have showed that the concentration of EGB increased, it could be seen a significant decrease in Survivin gene expression (P <0.01). Meanwhile, the TIP30 gene expression got a significant increase. Therefore, EGB can effectively inhibit ACC-2 cell Survivin gene expression in human with adenoid cysistic carcinoma of larcrimal gland as well as promoting TIP30 gene expression, inducing the ACC-2 cell apoptosis and inhibiting tumor cell proliferation, which provided a certain theoretical and experimental basis for the application of Chinese herbal medicinal ingredient in the treatment of tumors.