Risk factors for the development of cryptogenic stroke and the predictive value of right-to-left shunt in patent foramen ovale.

OBJECTIVE: The purpose of this study was to evaluate the relationship between the right-to-left shunt of the patent foramen ovale and the risk score for paradoxical embolism in cryptogenic stroke, as well as the risk factors for the development of cryptogenic stroke. PATIENTS AND METHODS: A retrospective analysis was performed on 257 patients with cryptogenic stroke who were diagnosed and treated in our hospital from February 2020 to January 2022 as a study group, and 98 patients who were diagnosed and treated at the Department of Neurology in our hospital at the same time and excluded from stroke, were selected as the control group. Transcranial Doppler ultrasound acoustic contrast testing was used to grade right-to-left shunts of patent foramen ovale. Clinical information of individuals who had cryptogenic strokes was examined. The correlation between the right-to-left shunt of patent foramen ovale and the risk score for both cryptogenic stroke and paradoxical embolism was analyzed. The factors affecting the occurrence of cryptogenic stroke were investigated. The correlation between right-to-left shunt and paradoxical embolism risk score was explored. Receiver operator characteristic curve (ROC) analysis was used to evaluate each factor's clinical usefulness in predicting the occurrence of cryptogenic stroke. RESULTS: No difference was observed in the history of hypertension, low-density lipoprotein, C-reactive protein and fibrinogen between the control group and the study group (p<0.05). In the study group with patent foramen ovale, the proportion of patients with grades I and II of the right-to-left shunt of patent foramen ovale was significantly lower than that in the control group, while the percentage of patients with grades III and IV was obviously greater than that in the control group (p<0.05). Right-to-left shunt grade, C-reactive protein, and fibrinogen were independent risk factors for cryptogenic stroke by logistic multivariate regression analysis (p<0.05). With an increase in the right-to-left shunt of the patent foramen ovale, patients' risk scores for paradoxical embolism increased considerably (p<0.05). In patients with cryptogenic stroke, the right-to-left shunt grade of the patent foramen ovale was positively connected with the paradoxical embolism risk score (r=0.331, p<0.001). ROC analysis results showed that the areas under the curves (AUC) of right-to-left shunt grading, C-reactive protein, and fibrinogen were 0.651, 0.871, and 0.779, respectively. The combination of the three indexes had an AUC of 0.908, a sensitivity of 87.90%, a specificity of 82.70%, and a Youden index of 0.706, indicating a high predictive value of the combination. CONCLUSIONS: The right-to-left shunt of patent foramen ovale was an independent risk factor for cryptogenic stroke, which was positively correlated with the paradoxical embolic risk score. Its combination with clinical serologic indexes had a high clinical value for predicting cryptogenic stroke.

Effects of different drainage methods on serum bile acid and hepatocyte apoptosis and regeneration after partial hepatectomy in rats with obstructive jaundice.

The aim of this study was to investigate the mechanism of hepatocyte apoptosis and regeneration after partial hepatectomy in obstructive jaundice (OJ) rats under different drainage methods of bile acid intervention. Forty male Sprague Dawley rats were randomly divided into five groups. An OJ rat model was established by the following protocols. Seven days after obstruction, an SD rats model with 70% partial hepatectomy was established by different drainage methods of OJ. Blood and liver tissue samples were collected from rats 72 h after surgery; 72 h after partial hepatectomy (PH), the liver regeneration rate, the expression of proliferating cell nuclear antigen (PCNA) and the level of mitotic index (MI) in the internal biliary drainage (IBD) group were higher than those in external biliary drainage (EBD) group (P less than 0.05). Those in the EBD group were higher compared to the OJ group (P less than 0.05). There was no significant difference among the IBD group, EBD+CA group and (SO) sham operation group (P>0.05). Bax expressions had the same trend as AI in the five groups. The expression of Bcl-2 was increased in the IBD group and EBD+CA group, which was statistically higher compared to the SO group (P less than 0.05). In conclusion, both internal and external drainage can relieve biliary obstruction. The difference in liver regeneration caused by external drainage and internal drainage may be attributed to the destruction of bile acid enterohepatic circulation, which increases hepatocyte apoptosis and affects liver regeneration.

Loop-tail phenotype in heterozygous mice and neural tube defects in homozygous mice result from a nonsense mutation in the Vangl2 gene.

N-ethyl-N-nitrosourea (ENU) is a powerful point mutagen that can generate random mutations. It has been used to generate mouse mutations to produce phenotypic models of human disease. Neural tube defects (NTD) are common birth defects in which the brain and/or spinal cord can be exposed; however, the mechanisms of these defects are poorly understood. Craniorachischisis is one type of NTD that bears a close resemblance to the phenotype of the loop-tail (Lp) mouse. Here we describe a C57BL/6J Lp mouse generated by ENU-induced mutagenesis. The mutation was mapped to the Vangl2 gene on chromosome 1, near markers D1Mit113 and D1Mit149. Sequence analysis of Vangl2 heterozygotes (Vangl2(m1Yzcm)/+) revealed a C/T transition mutation that resulted in substitution of a glutamine codon for a stop (nonsense) codon at position 449. The Vangl2 protein is involved in epithelium planar cell polarity. The predicted truncated protein would lack the PDZ-domain binding motif involved in protein-protein interaction; therefore, Vangl2(m1Yzcm) may be a loss-of-function mutant. Morphological and histological examination of homozygous mouse embryos revealed a neural tube closure defect that leads to craniorachischisis. This Vangl2(m1Yzcm) mouse represents a valuable model for the study of NTDs in humans.