Inhibition of SK Channels in VTA Affects Dopaminergic Neurons to Improve the Depression-Like Behaviors of Post-Stroke Depression Rats.

Purpose: This study aimed to investigate the effect of small-conductance calcium-activated potassium channels (SK channels) on the dopaminergic (DA) neuron pathways in the ventral tegmental area (VTA) during the pathogenesis of post-stroke depression (PSD) and explore the improvement of PSD by inhibiting the SK channels. Patients and Methods: Four groups of Sprague-Dawley rats were randomly divided: Control, PSD, SK channel inhibitor (apamin) and SK channel activator (CyPPA) groups. In both control and CyPPA groups, sham surgery was performed. In the other two groups, middle cerebral arteries were occluded. The behavioral indicators related to depression in different groups were compared. Immunofluorescence was used to measure the activity of DA neurons in the VTA, while qRT-PCR was used to assess the expression of SK channel genes. Results: The results showed that apamin treatment improved behavioral indicators related to depression compared to the PSD group. Furthermore, the qRT-PCR analysis revealed differential expression of the KCNN1 and KCNN3 subgenes of the SK channels in each group. Immunofluorescence analysis revealed an increase in the expression of DA neurons in the VTA of the PSD group, which was subsequently reduced upon apamin intervention. Conclusion: This study suggests that SK channel activation following stroke contributes to depression-related behaviors in PSD rats through increased expression of DA neurons in the VTA. And depression-related behavior is improved in PSD rats by inhibiting the SK channels. The results of this study provide a new understanding of PSD pathogenesis and the possibility of developing new strategies to prevent PSD by targeting SK channels.

Shuangdan Mingmu Capsule for Diabetic Retinopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Objective: To systematically evaluate the efficacy and safety of the Shuangdan Mingmu capsule in the treatment of diabetic retinopathy (DR). Methods: Common Chinese and English databases, including PubMed, Medline, Embase, VIP, Wanfang, and the Chinese National Knowledge Infrastructure (CNKI), were searched from their inception to May 31, 2022. According to the Cochrane Handbook, two reviewers independently evaluated and collected data on the included studies. Meta-analysis was performed by RevMan software 5.4. Results: Seven trials with a total of 835 patients were included. The clinical effectiveness rate was defined as the primary outcome, and the TCM symptom score, Chinese-Version Low Vision Quality of Life Questionnaire (CLVQOL) scores, macular thickness, hemorrhagic spot area, vascular endothelial growth factor levels, platelet-derived growth factor levels, and the incidence of adverse effects were the secondary outcome. The results of the meta-analysis showed that, compared with conventional medical treatment alone, the Shuangdan Mingmu capsule combined with conventional treatment could significantly improve the clinical effectiveness rate of treating DR (OR = 4.07, 95% CI (2.10, 7.89), p < 0.0001), and reduce the incidence of adverse reactions in DR patients (OR = 0.47, 95% CI (0.26, 0.86), p=0.01). In addition, other results showed that TCM symptom score(OR = -3.47, 95% CI (-3.84, -3.10), p < 0.00001); CLVQOL scores (OR = 23.93, 95% CI (21.37, 26.49), p < 0.00001); macular thickness (OR = -47.34, 95% CI (-50.67, 44.00), p < 0.00001); hemorrhagic spot area (OR = -0.91, 95% CI (-1.01, -0.81), p < 0.00001); vascular endothelial growth factor levels (OR = -45.76, 95% CI (-49.74, 41.79), p < 0.00001); platelet-derived growth factor levels (OR = -1.73, 95% CI (-2.15, -1.31), p < 0.00001). Conclusion: Compared with conventional treatment alone, the Shuangdan Mingmu capsule combined with conventional treatment is more effective and safer in the treatment of diabetic retinopathy. However, due to the limitations of the included studies, more high-quality studies are still needed to further assess the efficacy and safety of the Shuangdan Mingmu capsule in the treatment of diabetic retinopathy.

Verification and comparison of three prediction models of ischemic stroke in young adults based on the back propagation neural networks.

ABSTRACT: This work aims to explore risk factors for ischemic stroke in young adults and analyze the Traditional Vascular Risk Factors Model based on age, hypertension, diabetes, smoking history, and drinking history. Further, the Lipid Metabolism Model was analyzed based on lipoprotein a [LP (a)], high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein AI (apo AI), apolipoprotein B (apo B), and the Early Renal Injury Model based on urinary microalbuminuria/creatinine ratio (UACR). Besides, we estimated glomerular filtration rate (eGFR), cystatin C (Cys-C), homocysteine (Hcy), ß2 microglobulin (ß2m), and validated their predictive efficacy and clinical value for the development of ischemic stroke in young adults.We selected and retrospectively analyzed the clinical data of 565 young inpatients admitted to Zhejiang Provincial Hospital of Chinese Medicine between 2010 and 2020, 187 of whom were young stroke patients. A single-factor analysis was used to analyze the risk factors for stroke in young people and developed a traditional vascular risk factors model, a lipid metabolism model, and an early kidney injury model based on backpropagation (BP) neural networks technology to predict early stroke occurrence. Moreover, the prediction performance by the area under the receiver operating characteristics (ROC) curve (AUC) was assessed to further understand the risk factors for stroke in young people and apply their predictive role in the clinical setting.Single-factor analysis showed that ischemic stroke in young adults was associated with hypertension, diabetes, smoking history, drinking history, LP(a), HDL, LDL, apo AI, apo B, eGFR, Cys-C, and ß2m (P < .05). The BP neural networks technique was used to plot the ROC curves for the Traditional Vascular Risk Factors Model, the Lipid Metabolism Model, and the Early Kidney Injury Model in enrolled patients, and calculated AUC values of 0.7915, 0.8387, and 0.9803, respectively.The early kidney injury model precisely predicted the risk of ischemic stroke in young adults and exhibited a certain clinical value as a reference for morbidity assessment. Whereas the prediction performance of the Traditional Vascular Risk Factors Model and the Lipid Metabolism Model were inferior to that of the early kidney injury model.