Liaoning Provincial People's Hospital

The core pathological mechanisms of diabetic microvascular diseases, such as nephropathy, diabetic retinopathy (DR), and neuropathy, involve the dysfunction and loss of microvascular endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and pericytes (PCs). Conventional therapeutic approaches struggle to achieve structural repair and functional regeneration of damaged vessels. Induced pluripotent stem cell (iPSC) technology offers revolutionary prospects for an autologous, limitless source of functional vascular cells, significantly advancing regenerative medicine in the field of diabetic vascular complications. This review systematically summarizes recent developments in differentiating iPSCs into key microvascular cell types. Combined with advanced co-culture, three-dimensional (3D) modeling, organoids, and microfluidic chip technologies, these developments have not only deepened our understanding of diabetic microvascular pathology but also demonstrated substantial clinical potential in cell transplantation therapies, vascular tissue engineering constructs, and personalized drug screening.

The trimester-specific association of prenatal dietary patterns with intrauterine fetal growth and neonatal birth size is unclear. We evaluated the trimester-specific association of prenatal dietary patterns with intrauterine fetal growth and neonatal birth size. A prospective pre-birth cohort study included 1,857 mother-neonate pairs in China. Food frequency questionnaires were used to assess the maternal diet across three trimesters. we used generalized estimating equation models to examine the longitudinal associations of prenatal dietary patterns with intrauterine fetal growth and neonatal birth size. In addition, we used multinomial logistic regression models and multivariable linear regression models to estimate the trimester-specific associations. 5.0% and 6.8% of the neonates were low birth weight and macrosomia births, respectively. We observed longitudinal positive associations of maternal adherence to a "dairy-egg pattern" over three trimesters with the risk of macrosomia births [tertile 3 (T3) vs. tertile 1 (T1): odds ratio = 1.64, 95% confidence interval (CI): 1.01, 2.65], and the association was more pronounced in the first trimester (T3 vs. T1: relative risk ratio = 2.12, 95% CI: 1.08, 4.18). Higher adherence to the "dairy-egg pattern" and the "fish-seafood pattern" in the second and third trimesters were associated with higher and lower risk of estimated fetal weight>90th percentile during corresponding trimesters, respectively. Trimester-specific dietary patterns were differentially associated with fetal growth trajectory and neonatal birth size. These findings highlight the importance of trimester-tailored dietary guidance for optimizing fetal growth during pregnancy.

Although effective for atrophic acne scars, ablative fractional CO₂ laser (AFCL) causes unavoidable downtime and carries the potential for post-inflammatory hyperpigmentation (PIH). To evaluate the efficacy and safety of hydroxybutyl chitosan (HBC) in wound healing and to investigate the possible molecular mechanisms of HBC. Eighteen participants were enrolled in a split-face study, with each hemiface randomly assigned to receive either HBC or positive control therapy (PC: desonide cream, epidermal growth factor gel, and fusidic acid cream in combination) following AFCL. Clinical assessments included erythema, edema, pain, the time to decrustation, the skin barrier function, and melanin were assessed. In parallel, a mouse skin wound healing model was employed to investigate the effects of HBC. The expression of interferon regulatory factor 7 (IRF7) and cathepsin S (Ctss), as well as M1 and M2 macrophage polarization, was evaluated by immunohistochemistry and Western blot analysis of mouse skin tissues. Although HBC exhibited a slightly delayed onset of wound healing compared to the PC protocol, it achieved comparable outcomes by Days 7 and 28 between the groups. HBC showed more early pain but no steroid-related irritation and better moisturization. In mice, HBC demonstrated effects comparable to PC drugs, promoting macrophage M2 polarization and upregulating IRF7 and Ctss expression. HBC is effective and safe for promoting wound healing post AFCL. HBC upregulates IRF7 and Ctss expression and promotes macrophage M2 polarization. The expression of IRF7/CTSS may be correlated with M2 polarization of macrophages. ChiCTR2200063765.

Frozen shoulder (FS) is a condition that causes shoulder pain and restricted movement, primarily due to inflammation, fibrosis, and adhesion of the shoulder joint capsule. It commonly affects individuals aged 30 to 60 years. Factors such as diabetes, obesity, and shoulder trauma are known risk factors. Although current treatments include nonsteroidal anti-inflammatory drugs, steroid injections, and physical therapy, approximately 22.5% of patients do not respond well to conservative treatments and may require surgical intervention. The ADAMTS family is thought to play a significant role in joint diseases, and this study investigates its impact on FS. This study employed the Mendelian Randomization (MR) analysis method using genome-wide association studies (GWAS) data to analyze the causal relationships between the ADAMTS-5 and ADAMTS-13 genes and FS. By screening SNPs related to ADAMTS-1, ADAMTS-5, and ADAMTS-13, data analysis was performed using R software to verify the impact of these genes on FS pathogenesis. Additionally, co-location analysis was conducted to identify potential therapeutic targets. The MR analysis results indicate that ADAMTS-1-mediated ADAMTS-5 levels, along with the levels of ADAMTS-5 and ADAMTS-13 themselves, significantly increase the risk of FS. Co-expression localization analysis revealed that rs62217270, rs977151, and rs4962153 are potential targets for inhibiting ADAMTS-1, ADAMTS-5, and ADAMTS-13, respectively. In our study, ADAMTS-1, ADAMTS-5, and ADAMTS-13 were identified as potential risk factors contributing to the development of FS. The SNP rs62217270 may serve as a potential therapeutic target for FS by downregulating ADAMTS-5 expression through inhibition of ADAMTS-1. Additionally, rs977151 and rs4962153 were identified as potential targets for FS treatment via the reduction of ADAMTS-5 and ADAMTS-13 levels, respectively.

Temporomandibular joint (TMJ) synovitis is a chronic inflammatory condition prevalent in temporomandibular disorders, characterized by synovial inflammation and bone degradation. Quercetin, a natural flavonoid with diverse bioactive properties, is investigated for its potential in ameliorating TMJ synovitis by targeting the p38 MAPK pathway. Using network pharmacology and in vitro and in vivo models, the effects of quercetin on synoviocytes and inflammatory responses were evaluated. Results showed quercetin's significant inhibition of synoviocyte proliferation, promotion of apoptosis and reduction of inflammatory cytokines. Moreover, quercetin demonstrated stability in binding to critical targets like MAPK14 and led to downregulation of phosphorylated p38 MAPK and JNK. In vivo, quercetin improved synovial tissue architecture and mitigated bone destruction. Mechanistic studies confirmed the dependency of effects of quercetin on the p38 MAPK pathway, supported by functional experiments using pathway agonists and inhibitors. The present study underscored the potential of quercetin in treating TMJ synovitis by modulating inflammatory signaling, promoting cell apoptosis and preserving bone integrity, thereby offering novel insights into therapeutic strategies for TMJ-related synovitis.

Epilepsy, antiepileptic drugs (AEDs), and adjuvant treatments may correlate with the development of subclinical atherosclerosis. We performed a systematic review and meta-analysis to evaluate the effects of epilepsy, AEDs, and adjuvant treatments on the structural and functional markers of subclinical atherosclerosis represented by carotid intima-media thickness (cIMT), epicardial adipose tissue thickness (EATT), and flow-mediated vasodilation (FMD). Weighted mean differences (WMD) and corresponding 95% confidence intervals (CIs) were analyzed. Thirty-one studies were included with 9 different outcomes. Compared with controls, the epileptic patients demonstrated significantly thicker cIMT (WMD [95% CI] = 0.063 [0.045-0.080], P < .001) and EATT (WMD [95% CI] = 1.985 [1.630-2.341], P < .001). There was no significant difference in FMD (P > .050). Moreover, cIMT was still thicker in the epileptic patients on old AEDs compared with those on new AEDs (WMD [95% CI] = 0.038 [0.000-0.076], P = .050), on multi-AEDs compared with on mono-AEDs (WMD [95% CI] = 0.025 [0.021-0.029], P < .001), and on enzyme-inducing AEDs compared with on non-enzyme-inducing AEDs (WMD [95% CI] = 0.027 [0.006-0.047], P = .011). No significant differences in cIMT were detected in any comparison of adjuvant treatments (ketogenic diet, Atkins diet, and folic acid supplements; all P > .050). Epilepsy and AEDs, especially old AEDs, multi-AEDs, and enzyme-inducing AEDs, could exacerbate the development of subclinical atherosclerosis. Early prevention as well as timely intervention for subclinical atherosclerosis should be considered for these patients.

Abstract Background Hypertrophic cardiomyopathy (HCM) is a genetic disorder that contributes to disabling symptoms, heart failure, and premature death across all age groups. Echocardiography serves as the primary diagnostic tool for HCM; however, its diagnosis is often delayed or missed due to various factors. Therefore, earlier and more accurate identification of HCM patients is crucial. Currently, there is a paucity of population-based screening studies for HCM, and large-scale epidemiological studies on HCM prevalence are lacking in China. Purpose To investigate the detection rate and echocardiographic characteristics of patients with HCM phenotypes (and their major subtypes) identified by echocardiography in year 2023 across echocardiography databases from nine large medical centers in China. Methods This is a multicenter, cross-sectional study. Data were collected from the echocardiography databases of participating centers, including all outpatients, emergency patients, and inpatients who underwent echocardiography from January 1st, 2023, to December 31st, 2023. All adult patients with HCM phenotypes identified by echocardiography were enrolled. For patients who underwent multiple echocardiographic examinations, the results from the first examination within the study period were used for analysis. According to current guideline recommendations, an end-diastolic wall thickness ≥15 mm anywhere in the left ventricle was identified as an HCM phenotype. Applying a left ventricular outflow tract obstruction ≥30 mmHg (when documented), we further identified obstructive HCM (oHCM). Results Among 655,383 echocardiographic examinations conducted in 2023 across nine medical centers in mainland China, 1,925 patients met the diagnostic criteria for HCM phenotype. Thus, the detection rate of HCM in this cohort was approximately 0.29% (Figure 1). Among patients with HCM phenotype, the mean age was 59.1 ± 15.0 years, and 71.5% were male. The maximum left ventricular wall thickness averaged 18.9 ± 3.9 mm in all HCM phenotype patients. Of these, 172/1,924 (8.9%) met the diagnostic criteria for obstructive HCM (oHCM). In patients with oHCM, 91/172 (52.9%) exhibited a left ventricular outflow tract peak pressure gradient of ≥50 mmHg on either rest or stimulation test. Patients with oHCM exhibited significantly greater maximum left ventricular wall thickness and a higher incidence of moderate to severe mitral regurgitation compared to non-oHCM patients (Table 1). Conclusion In this multicenter echocardiography cohort from China, the detection rate of HCM phenotypes in year 2023 was approximately 0.29%, which aligns with the prevalence reported in other large-scale epidemiological studies on hypertrophic cardiomyopathy. A relatively lower detection rate of obstructive HCM phenotype reinforces the necessity of stimulation test training.Figure 1 Table 1