CCDC88C variants are associated with focal epilepsy and genotype-phenotype correlation.

CCDC88C gene, which encodes coiled-coil domain containing 88C, is essential for cell communication during neural development. Variants in the CCDC88C caused congenital hydrocephalus, some accompanied by seizures. In patients with epilepsy without acquired etiologies, we performed whole-exome sequencing (trio-based). Two de novo and two biallelic CCDC88C variants were identified in four cases with focal (partial) epilepsy. These variants did not present or had low frequencies in the gnomAD populations and were predicted to be damaging by multiple computational algorithms. Patients with de novo variants presented with adult-onset epilepsy, whereas patients with biallelic variants displayed infant-onset epilepsy. They all responded well to anti-seizure medications and were seizure-free. Further analysis showed that de novo variants were located at crucial domains, whereas one paired biallelic variants were located outside the crucial domains, and the other paired variant had a non-classical splicing and a variant located at crucial domain, suggesting a sub-molecular effect. CCDC88C variants associated with congenital hydrocephalus were all truncated, whereas epilepsy-associated variants were mainly missense, the proportion of which was significantly higher than that of congenital hydrocephalus-associated variants. CCDC88C is potentially associated with focal epilepsy with favorable outcome. The underlying mechanisms of phenotypic variation may correlation between genotype and phenotype.

Mangiferin alleviates diabetic pulmonary fibrosis in mice via inhibiting endothelial-mesenchymal transition through AMPK/FoxO3/SIRT3 axis.

Diabetes mellitus results in numerous complications. Diabetic pulmonary fibrosis (DPF), a late pulmonary complication of diabetes, has not attracted as much attention as diabetic nephropathy and cardiomyopathy. Mangiferin (MF) is a natural small molecular compound that exhibits a variety of pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetes, and anti-fibrosis effects. In this study, we investigated whether long-term diabetes shock induces DPF, and explored whether MF had a protective effect against DPF. We first examined the lung tissues and sections of 20 diabetic patients obtained from discarded lung surgical resection specimens and found that pulmonary fibrosis mainly accumulated around the pulmonary vessels, accompanied by significantly enhanced endothelial-mesenchymal transition (EndMT). We established a mouse model of DPF by STZ injections. Ten days after the final STZ injection, the mice were administered MF (20, 60 mg/kg, i.g.) every 3 days for 4 weeks, and kept feeding until 16 weeks and euthanized. We showed that pulmonary fibrotic lesions were developed in the diabetic mice, which began around the pulmonary vessels, while MF administration did not affect long-term blood glucose levels, but dose-dependently alleviated diabetes-induced pulmonary fibrosis. In human umbilical vein endothelial cells (HUVECs), exposure to high glucose (33.3 mM) induced EndMT, which was dose-dependently inhibited by treatment with MF (10, 50 µM). Furthermore, MF treatment promoted SIRT3 expression in high glucose-exposed HUVECs by directly binding to AMPK to enhance the activity of FoxO3, which finally reversed diabetes-induced EndMT. We conclude that MF attenuates DPF by inhibiting EndMT through the AMPK/FoxO3/SIRT3 axis. MF could be a potential candidate for the early prevention and treatment of DPF.

Diagnostic performance of acoustic radiation force impulse for acute pancreatitis: A meta-analysis.

OBJECTIVE: The objective of this meta-analysis is to evaluate the diagnostic performance of acoustic radiation force impulse (ARFI) in acute pancreatitis (AP) patients. METHODS: PubMed, Web of Science, Embase, Wanfang, Chinese Biological Medicine databases, and Chinese Biomedical Literature Service System were searched for relevant studies to explore the potential diagnostic performance of ARFI in AP from inception to November 2023. STATA 14.0 was used to analyze the standardized mean difference (SMD) with 95% confidence interval (CI), pooled sensitivity, specificity, area under the curve, meta-regression analysis, sensitivity analysis, and publication bias. RESULTS: Nine studies, involving 533 AP patients and 585 healthy controls, were included. AP patients had significantly higher ARFI levels than healthy controls (SMD: 3.13, 95% CI: 1.88-4.39, P = .001). The area under the curve of ARFI for diagnosing AP was 0.99 (95% CI: 0.98-1.00), with 98% sensitivity and 94% specificity. Meta-regression identified the study region and study period as the sources of heterogeneity. Sensitivity analysis showed that the exclusion of any single study did not materially alter the overall combined effect. No evidence of publication bias was observed in the included studies. CONCLUSION: This meta-analysis demonstrated that ARFI exerted satisfactory diagnostic performance in AP.

Association between stress hyperglycemia ratio and in-hospital outcomes: findings from the improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) Project.

BACKGROUND: Stress hyperglycemia ratio (SHR) could provide accurate information on the acute status of hyperglycemia. The relationship between SHR and acute coronary syndrome (ACS) prognosis remains unclear. This study was conducted to identity the association between SHR and in-hospital outcomes in patients with ACS. METHODS: A total of 12,010 patients were eventually enrolled in the study. The relationship between SHR and in-hospital major adverse cardiovascular events (MACEs) was then modeled by restricted cubic spline (RCS) curves, and all patients were divided into three groups according to the results. The multivariate logistic regression analysis was used to determine the associations between the SHR and in-hospital outcomes, described as odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were also performed on different diseases. RESULTS: The median age of this cohort was 63 (54, 71) years old, and 8942 (74.5%) were male. Group 1 was defined as SHR < 0.6 (n = 426), Group 2 was defined as SHR between 0.6 and 1 (n = 5821), and Group 3 was defined as SHR > 1 (n = 5763). Compared with Group 2, Group 1 (OR = 1.891, 95% CI: 1.028-3.479, P < 0.001) and Group 3 (OR = 1.868, 95% CI: 1.434-2.434, P < 0.001) had higher risks of suffering from in-hospital MACEs. SHR was associated with higher risks of in-hospital MACEs in the subgroups of DM [OR = 2.282, 95% CI: 1.477-3.524). CONCLUSIONS: Both low and high SHR levels were independently associated with in-hospital MACEs. Young males with DM, hypertension, and decreased renal function had much higher risks of suffering from SHR-correlated MACEs.

[Retracted] Effect of metformin on cell proliferation, apoptosis, migration and invasion in A172 glioma cells and its mechanisms.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the cell invasion and migration assay data shown in Fig. 6 and the cell proliferation assay experiments shown in Fig. 2 were strikingly similar to data appearing in different form in other articles by different authors; furthermore, in Fig. 2, for the '10 mM metformin' experiment, certain of the glioma cells appeared to be strikingly similar to other cells contained within the same data panels. Owing to the fact that the contentious data in the above article had already been published elsewhere or were under consideration for publication prior to its submission to Molecular Medicine Reports, and owing to concerns with the authenticity of certain of the data, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 20: 887­894, 2019; DOI: 10.3892/mmr.2019.10369].

Data-Driven Analysis Reveals Cortical Infarction Patterns Correlated With Inflammation and Prognosis: A Retrospective, Multicenter Cohort Study.

BACKGROUND: We aim to identify the distinct lesion patterns and regions associated with functional outcome and inflammation in patients with acute ischemic stroke, and investigate whether the association between lesion patterns and functional outcome was mediated by inflammation. METHODS AND RESULTS: We performed nonnegative matrix factorization to derived low-dimensional lesion patterns (atoms), and Bayesian linear regression models were applied to explore the associations of lesion patterns with inflammatory factors including high-sensitivity C-reactive protein and interleukin-6, as well as functional outcome (defined as modified Rankin Scale score at 3 months). The difference distribution mean and 95% highest probability density interval (HPDI) were calculated. Mediation analysis was used to examine the mediating effects of inflammation on the relationships between lesion patterns and functional outcome. Seven lesion patterns were derived from 5914 patients with acute ischemic stroke. Lesion patterns distributed in the cortical regions were associated with inflammatory response, including atom 1 (interleukin-6: mean, 0.113 [95% HPDI, 0.073-0.162]; high-sensitivity C-reactive protein: mean, 0.082 [95% HPDI, 0.038-0.123]) and atom 4 (interleukin-6: mean, 0.113 [95% HPDI, 0.071-0.167]; high-sensitivity C-reactive protein: mean, 0.108 [95% HPDI, 0.058-0.165]). These lesion patterns were also significantly associated with functional outcome (atom 1: mean, 1.958 [95% HPDI, 1.538-2.383]; atom 4: mean, 2.245 [95% HPDI, 1.773-2.741]). Mediation analysis suggested that interleukin-6 explained 15.34% and 7.47% in the association of atom 1 and atom 4 with functional outcome, respectively. CONCLUSIONS: Certain lesion patterns that are associated with both inflammation and functional outcome of acute ischemic stroke, especially cortical infarction, may play a role in functional outcome through modulating inflammatory reactions.