Patent Foramen Ovale Closure for Migraineurs with Massive Right-to-Left Shunt and White Matter Lesions: An Exploration on Curative Effects.

Objective: This study aims to investigate the therapeutic efficacy of patent foramen ovale (PFO) closure in migraine patients with a massive right-to-left shunt (RLS) and white matter lesions (WMLs). Methods: The research focused on migraine patients with a massive RLS who underwent PFO closure in our hospital from June 2020 to June 2021. The study included 51 patients without WMLs (control group, CG) and 27 patients with WMLs (observation group, OG). A 12-month postoperative follow-up survey was conducted to assess headache episodes (frequency and duration), evaluated using the Headache Impact Test-6 (HIT-6) and the Pain Intensity Visual Analog Scale (VAS). The psychological state was also evaluated using the Hamilton Anxiety and Depression Scale (HAMA, HAMD). Adverse reactions during the follow-up were recorded. Results: No significant differences in perioperative and prognostic adverse reactions were observed between OG and CG (P > .05). Both groups showed a reduction in postoperative headache episodes and pain intensity. However, the OG exhibited higher frequency and duration of headache episodes and elevated HIT-6 and VAS scores, resulting in lower clinical efficacy (P < .05). Postoperatively, both groups demonstrated reductions in HAMA and HAMD, with CG showing lower scores compared to OG (P < .05). Logistic regression analysis identified the course of the disease, HIT-6 score, and the presence of WMLs as independent risk factors for the efficacy of PFO closure (P < .05). Conclusions: PFO closure proves effective and safe in treating migraine patients with RLS. However, for those with WMLs, clinical attention should be directed toward the treatment of WMLs.

Short communication: An inducible CRISPR/dCas9 gene repression system in Lactococcus lactis.

Lactococcus lactis, one of the most important probiotic lactic acid bacteria (LAB), is widely used in the dairy industry as a cell factory for recombinant protein production. Currently, a nisin-controlled inducible expression system is used for this purpose and represents the only commercial expression system in LAB. However, the available genetic modification methods are rather limited for modulating gene expression in L. lactis. Here, we developed a 2-plasmid system for gene transcription repression in L. lactis NZ9000 that uses inducible clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9. An inducible promoter Pnisin was used to drive the expression of dCas9 from Streptococcus pyogenes, whereas a strong constitutive promoter P44 drove single guide RNA expression for single or multiple target genes. dCas9 enabled CRISPR interference-mediated silencing of single or multiple target genes with significant reduction of gene expression, up to 99%. In addition, LLNZ_07335, a putative penicillin acylase, was identified as bile salt hydrolase for bile salt resistance in NZ9000 using this system. To our knowledge, this report is the first for a functional gene for bile salt tolerance in L. lactis. Overall, our work introduces a new gene repression tool for various applications in L. lactis or other LAB.