CCKA

Biliary dyskinesia is a relatively common gastrointestinal disease that is increasing in incidence as living standards improve. However, its underlying pathogenesis remains unclear, hindering the development of therapeutic drugs. Recently, "Expression and functional study of cholecystokinin-A receptors on the interstitial Cajal-like cells of the guinea pig common bile duct" demonstrated that cholecystokinin (CCK) regulates the contractile function of the common bile duct through interaction with the CCK-A receptor in interstitial Cajal-like cells, contributing to improving the academic understanding of biliary tract dynamics and providing emerging directions for the pathogenesis and clinical management of biliary dyskinesia. This letter provides a brief overview of the role of CCK and CCK-A receptors in biliary dyskinesia from the perspective of animal experiments and clinical studies, and discusses prospects and challenges for the clinical application of CCK and CCK-A receptors as potential therapeutic targets.

DNA methylation plays an important role in the occurrence and development of age-related cataracts (ARC). This study aims to reveal potential epigenetic biomarkers of ARC by detecting modifications to the DNA methylation patterns of genes shown to be related to ARC by transcriptomics. The MethylationEPIC BeadChip (850K) was used to analyze the DNA methylation levels in ARC patients and unaffected controls, and the Pearson correlation test was used to perform genome-wide integration analysis of DNA methylation and transcriptome data. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to perform functional analysis of the whole genome, promoter regions (TSS1500/TSS200), and the associated differentially methylated genes (DMG). Pyrosequencing was used to verify the methylation levels of the selected genes. The results showed that, compared with the control group, a total of 52,705 differentially methylated sites were detected in the ARC group, of which 13,858 were hypermethylated and 38,847 were hypomethylated. GO and KEGG analyses identified functions related to the cell membrane, the calcium signaling pathway, and their possible molecular mechanisms. Then, 57 DMGs with negative promoter methylation correlations were screened by association analysis. Pyrosequencing verified that the ARC group had higher methylation levels of C3 and CCKAR and lower methylation levels of NLRP3, LEFTY1, and GPR35 compared with the control group. In summary, our study reveals the whole-genome DNA methylation patterns and gene expression profiles in ARC, and the molecular markers of methylation identified herein may aid in the prevention, diagnosis, treatment, and prognosis of ARC.

To develop and validate a finite element (FE) model of a sacral pedicle subtraction osteotomy (S1-PSO) and to compare biomechanical properties of various multi-rod configurations to stabilize S1-PSOs.

A previously validated FE spinopelvic model was used to develop a 30° PSO at the sacrum. Five multi-rod techniques spanning the S1-PSO were made using 4 iliac screws and a variety of primary rods (PR) and accessory rods (AR; lateral: Lat-AR or medial: Med-AR). All constructs, except one, utilized a horizontal rod (HR) connecting the iliac bolts to which PRs and Med-ARs were connected. Lat-ARs were connected to proximal iliac bolts. The simulation was performed in two steps with the acetabula fixed. For each model, PSO ROM and maximum stress on the PRs, ARs, and HRs were recorded and compared. The maximum stress on the L5-S1 disc and the PSO forces were captured and compared.

Highest PSO ROMs were observed for 4-Rods (HR + 2 Med-AR). Constructs consisting of 5-Rods (HR + 2 Lat-ARs + 1 Med-AR) and 6-Rods (HR + 2 Lat-AR + 2 Med-AR) had the lowest PSO ROM. The least stress on the primary rods was seen with 6-Rods, followed by 5-Rods and 4-Rods (HR + 2 Lat-ARs). Lowest PSO forces and lowest L5-S1 disc stresses were observed for 4-Rod (Lat-AR), 5-Rod, and 6-Rod constructs, while 4-Rods (HR + Med-AR) had the highest.

In this first FE analysis of an S1-PSO, the 4-Rod construct (HR + Med-AR) created the least rigid environment and highest PSO forces anteriorly. While 5- and 6-Rods created the stiffest constructs and lowest stresses on the primary rods, it also jeopardized load transfer to the anterior column, which may not be favorable for healing anteriorly. A balance between the construct's rigidity and anterior load sharing is essential.