ObjectiveTo observe the clinical efficacy and safety of Shenshuai Guanchang prescription in improving the intestinal barrier function，reducing non-indole uremic toxins，ameliorating micro-inflammatory state，and delaying renal function progression in non-dialysis patients with chronic kidney disease （CKD） stage 4-5. MethodsA total of 80 patients with CKD stage 4-5 who did not receive dialysis replacement therapy and were diagnosed with the syndrome of spleen and kidney deficiency，blood stasis and dampness turbidity were randomly assigned into a control group and a treatment group，with 40 patients in each group. The control group received conventional basic treatment and Western medicine symptomatic treatment，while the treatment group received combined intervention with Shenshuai Guanchang prescription through retention enema in addition to the treatment of the control group. Both groups had a treatment course of 4 weeks. The two groups were compared regarding the changes in urine toxin indicators ［p-cresyl sulfate （PCS） and trimethylamine oxide （TMAO）］，intestinal barrier indicators ［D-lactic acid （D-LA），lipopolysaccharide （LPS），and intestinal fatty acid-binding protein （I-FABP）］，renal function indicators ［serum creatinine （SCr），blood urea nitrogen （BUN），and estimated glomerular filtration rate （eGFR）］，and micro-inflammatory state indicators ［interleukin-6 （IL-6），tumor necrosis factor-α （TNF-α），and neutrophil-to-lymphocyte ratio （NLR）］ before and after treatment. The therapeutic effects were evaluated from three aspects：The efficacy regarding traditional Chinese medicine （TCM） symptom scores，the efficacy regarding laboratory indicators，and comprehensive efficacy. The safety of the clinical research drugs used by both groups of patients was also observed. ResultsA total of 37 cases in the treatment group and 38 cases in the control group completed the observation. After treatment，the treatment group showed declined levels of PCS，TMAO，D-LA，SCr，TNF-α，and NLR，spleen and kidney deficiency symptom score，blood stasis and dampness symptom score，and total symptom score （P<0.05），and increased eGFR （P<0.05）. Moreover，the treatment group had lower levels of PCS，TMAO，D-LA，I-FABP，IL-6，and TNF-α，spleen and kidney deficiency symptom score，blood stasis and dampness symptom score，and total symptom score （P<0.05），higher response rate regarding TCM symptoms （χ²=6.68，P<0.05），and higher comprehensive efficacy （χ²=4.08，P<0.05） than the control group. No significant abnormalities were observed in the safety indicators of the two groups of patients. During the treatment period，adverse reactions were reduced after symptomatic treatment，and no serious adverse reactions occurred. ConclusionShenshuai Guanchang prescription can alleviate the clinical symptoms，improve the intestinal barrier function，reduce non-indole-type uremic toxins，alleviate the micro-inflammatory state，and has good clinical application safety of non-dialysis patients with CKD stage 4-5.

OBJECTIVE To investigate the effect and potential mechanism of Ziyin Mingmu Formula in treating age-related mac-ular degeneration(AMD)by combining network pharmacology with animal model validation.METHODS Active ingredients of Ziyin Mingmu Formula were obtained from the TCMSP and BATMAN databases,and their targets were searched using the PharmMapper da-tabase.AMD disease targets were identified using the GeneCards,DrugBank,OMIM,and TTD databases.Venny analysis was per-formed to identify the intersection of active ingredient and disease targets.A protein-protein interaction(PPI)network was constructed using the String database,and core targets were screened using Cytoscape 3.9.0 software.KEGG pathway enrichment analysis was per-formed using the DAVID database.Molecular docking of key active ingredients with core targets was performed using Autodock software.A laser-induced mouse choroidal neovascularization(CNV)model was used.Optical coherence tomography angiography(OCTA)was used to assess CNV area in vivo,immunofluorescence staining was used to assess CNV area on choroidal flat mounts,and Western blot analysis was used to examine the expression of proteins involved in the vascular endothelial growth factor(VEGF)pathway.RESULTS Network pharmacology analysis identified 221 active ingredients in the Ziyin Mingmu Formula.PPI analysis i-dentified 29 core targets,including SRC,protein kinase B(AKT1),mitogen-activated protein kinase 1(MAPK1),and heat shock protein 90α family class A member 1(HSP90AA1).KEGG analysis revealed that the VEGF signaling pathway was the most highly en-riched.Molecular docking revealed that the core targets SRC,AKT1,MAPK1,and HSP90AA1 had good binding affinity with the main active ingredients,diosmetin,catechin,vestitol,and licochalcone A.Animal experiments showed that the Ziyin Mingmu Formula significantly reduced CNV area in model mice,downregulated VEGF protein expression,decreased VEGFR2,p38,and ERK1/2 pro-tein phosphorylation levels,and inhibited the VEGF signaling pathway.CONCLUSION Ziyin Mingmu Formula may inhibit CNV for-mation by regulating the VEGF signaling pathway.

OBJECTIVE To investigate the effect and potential mechanism of Ziyin Mingmu Formula in treating age-related mac-ular degeneration(AMD)by combining network pharmacology with animal model validation.METHODS Active ingredients of Ziyin Mingmu Formula were obtained from the TCMSP and BATMAN databases,and their targets were searched using the PharmMapper da-tabase.AMD disease targets were identified using the GeneCards,DrugBank,OMIM,and TTD databases.Venny analysis was per-formed to identify the intersection of active ingredient and disease targets.A protein-protein interaction(PPI)network was constructed using the String database,and core targets were screened using Cytoscape 3.9.0 software.KEGG pathway enrichment analysis was per-formed using the DAVID database.Molecular docking of key active ingredients with core targets was performed using Autodock software.A laser-induced mouse choroidal neovascularization(CNV)model was used.Optical coherence tomography angiography(OCTA)was used to assess CNV area in vivo,immunofluorescence staining was used to assess CNV area on choroidal flat mounts,and Western blot analysis was used to examine the expression of proteins involved in the vascular endothelial growth factor(VEGF)pathway.RESULTS Network pharmacology analysis identified 221 active ingredients in the Ziyin Mingmu Formula.PPI analysis i-dentified 29 core targets,including SRC,protein kinase B(AKT1),mitogen-activated protein kinase 1(MAPK1),and heat shock protein 90α family class A member 1(HSP90AA1).KEGG analysis revealed that the VEGF signaling pathway was the most highly en-riched.Molecular docking revealed that the core targets SRC,AKT1,MAPK1,and HSP90AA1 had good binding affinity with the main active ingredients,diosmetin,catechin,vestitol,and licochalcone A.Animal experiments showed that the Ziyin Mingmu Formula significantly reduced CNV area in model mice,downregulated VEGF protein expression,decreased VEGFR2,p38,and ERK1/2 pro-tein phosphorylation levels,and inhibited the VEGF signaling pathway.CONCLUSION Ziyin Mingmu Formula may inhibit CNV for-mation by regulating the VEGF signaling pathway.

The key pathological feature of age-related macular degeneration(AMD)is dysfunction of retinal pigment epithelial cells.Cell adhesion,serving as the biological basis for dynamic interactions between cells and between cells and the extracellular matrix,regulates tissue homeostasis through transmembrane signaling networks mediated by adhesion molecules.Studies have shown that the aberrant expression of E-cadherin,which offers advantages such as dynamic plas-ticity,tissue specificity,and signal transduction capability,is closely associated with the pathological mechanism of AMD.Targeting E-cadherin-related molecules may thus serve as a potential strategy for AMD intervention.This article reviews re-cent advances in the molecular regulatory mechanisms and therapeutic research concerning E-cadherin in AMD,aiming to provide a theoretical basis for its clinical translation.

The key pathological feature of age-related macular degeneration(AMD)is dysfunction of retinal pigment epithelial cells.Cell adhesion,serving as the biological basis for dynamic interactions between cells and between cells and the extracellular matrix,regulates tissue homeostasis through transmembrane signaling networks mediated by adhesion molecules.Studies have shown that the aberrant expression of E-cadherin,which offers advantages such as dynamic plas-ticity,tissue specificity,and signal transduction capability,is closely associated with the pathological mechanism of AMD.Targeting E-cadherin-related molecules may thus serve as a potential strategy for AMD intervention.This article reviews re-cent advances in the molecular regulatory mechanisms and therapeutic research concerning E-cadherin in AMD,aiming to provide a theoretical basis for its clinical translation.

OBJECTIVE To evaluate the clinical efficacy of modified Zhujing Pills in the treatment of dry age-related macular degeneration(AMD)of liver and kidney insufficiency type.METHODS 64 patients with dry AMD of liver and kidney insufficiency type were randomly divided into an experimental group and a control group,32 patients each.The control group was given oral treat-ment with Laishiding capsules,and the experimental group was given oral treatment with modified Zhujing Pills granules.The treatment course for both groups was 3 months.Before and after treatment,the patients in the two groups were observed for TCM syndrome scores,visual acuity,fundus autofluorescence(AF),changes in drusen area within 5 mm of the fovea,and plasma superoxide dis-mutase(SOD),glutathione peroxidase(GSH-Px)activity and malondialdehyde(MDA)levels.RESULTS After treatment,the scores of TCM syndromes in the experimental group were significantly reduced(P＜0.05,P＜0.01),and the efficacy of TCM syn-dromes was better than that of the control group(P＜0.01);the visual acuity of the patients in the experimental group was significantly improved,AF was significantly weakened and the area of drusen was reduced(P＜0.05,P＜0.01),which were better than those in the control group(P＜0.05);the plasma SOD and GSH-Px activities of the experimental group were increased,and the MDA level was significantly lowered(P＜0.05,P＜0.01),which were better than the control group(P＜0.05).CONCLUSION Modified Zhujing Pills can reduce fundus AF intensity,decrease macular drusen area,improve visual acuity,and reduce TCM syndrome scores in pa-tients with dry AMD.The therapeutic mechanism may be related to its antioxidant effect.

Age-related macular degeneration(ARMD)is the leading cause of blindness in the elderly. Studies have shown that the regulation disorder of extracellular matrix(ECM)is one of the important characteristics of ARMD, and its damage can be sustained throughout the disease course. Additionally, various cell types participate in the formation and abnormal deposition of ECM under the control of multiple signals. Subsequently, they transmit signals that regulate adhesion, migration, proliferation, apoptosis, survival or differentiation, which lead to the destruction of the retinal and choroidal microenvironment, immune dysfunction, infiltrative inflammatory cell differentiation, neovascularization and epithelial mesenchymal transformation, and ultimately lead to subretinal fibrosis, scarring and severe visual impairment in advanced ARMD. Therefore, increasing attention has been paid to the role of ECM in ARMD in recent years. This article reviews the relationship between retinal ECM and ARMD and the role between ECM and various types of cells in ARMD, hoping to provide guidance for the research direction of ARMD treatment.

Objective:To study the effect of ZhuJing pill variant formula medicated serum on hydrogen peroxide (H 2O 2)-induced epithelial-mesenchymal transition (EMT) of human retinal pigment epithelial (ARPE-19) cells and its mechanism. Methods:Thirty female SPF grade SD rats aged 2 months old were selected.The rats were randomized into blank control group and Zhujing pill variant formula group according to random number table method, with 15 in each group, which were intragastrically administered with normal saline and ZhuJing pill variant formula solution for 7 days accordingly to prepare blank control serum and medicated serum.ZhuJing pill variant formula medicated serum was prepared with SD rats.ARPE-19 cells were divided into normal control group, model control group, blank serum group as well as 2.5%, 5.0% and 10.0% medicated serum groups, SB216763 group and SB216763+ medicated serum group.Normal and blank control groups were cultured in normal culture medium, while the other six groups were cultured in blank rat serum medium, medicated serum medium of corresponding concentration, 10 μmol/L SB216763 medium and 10 μmol/L SB216763+ 10.0% medicated serum medium, respectively.Normal control group was routinely cultured, while the other groups were routinely cultured for 24 hours, and then added with H 2O 2 with the final concentration of 200 μmol/L for 24 hours.Cell viability was assessed by cell counting kit-8 (CCK-8) assay, and cell migration ability was detected by Transwell assay.Intracellular reactive oxygen species (ROS) level was detected by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay, and MDA level was identified by sulfhydryl barbituric acid assay.The expression levels of Nrf2 pathway related proteins including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), quinone oxidoreductase 1 (NQO-1) and EMT-related proteins including transforming growth factor-β2 (TGF-β2), protein kinase B (AKT), glycogen synthase kinase-3β (GSK-3β), snail family zinc finger 1 (SNAIL1), α-smooth muscle actin (α-SMA), epithelial cadherin (E-cadherin) in cells were measured by western blot assay.The use and care of animals complied with Regulations for the Administration of Affairs Concerning Experimental Animals. Results:There was no significant difference in cell survival rate among blank serum group, 2.5%, 5.0% and 10.0% medicated serum groups ( F=0.163, P>0.05). The cell survival rates were (100.50±5.91)%, (60.87±4.30)%, (73.27±4.46)%, (80.73±5.67)% and (89.90±4.97)% in normal control group, model control group, 2.5%, 5.0% and 10.0% medicated serum groups, and the number of migrating cells was (84.67±8.33), (222.33±13.58), (215.67±10.02), (174.67±10.60), (143.67±8.02) and (107.67±6.66) pcs/visual field in normal control group, model control group, blank serum group, 2.5%, 5.0% and 10.0% medicated serum groups, respectively, with significant differences among the groups ( F=26.628, 99.289; both at P<0.01). The contents of ROS and MDA in model control group were significantly increased in comparison with normal control group (both at P<0.01). The contents of ROS and MDA of 2.5%, 5.0% and 10.0% medicated serum groups were significantly decreased in comparison with model control group (all at P<0.01). The relative expression levels of SNAIL1, α-SMA, TGF-β2, p-AKT and p-GSK-3β proteins were significantly higher and the relative expression level of E-cadherin protein was significantly lower in model control group compared with normal control group, 2.5%, 5.0% and 10.0% medicated serum groups (all at P<0.05). Compared with normal control group, the relative expression level of cytoplasmic Nrf2 in model control group was decreased, while the relative expression levels of nuclear Nrf2, HO-1 and NQO-1 were increased, and the differences were statistically significant (all at P<0.05). Compared with model control group, the relative expression levels of cytoplasmic Nrf2 in 2.5%, 5.0% and 10.0% medicated serum groups were reduced, and the relative expression levels of nuclear Nrf2, HO-1 and NQO-1 were enhanced, and the differences were statistically significant (all at P<0.01). Compared with model control group, the relative expression level of cytoplasmic Nrf2 in SB216763 group was decreased, and the relative expression level of nuclear Nrf2 was increased, and the differences were statistically significant (both at P<0.05). Compared with SB216763 group, the relative expression levels of cytoplasmic Nrf2, SNAIL1 and α-SMA in SB216763+ medicated serum group were decreased, and the relative expression levels of nuclear Nrf2 and E-cadherin protein were increased, and the differences were statistically significant (both at P<0.05). Conclusions:ZhuJing pill variant formula medicated serum can inhibit H 2O 2-induced EMT in ARPE-19 cells.The mechanism may be related to the inhibition of AKT/GSK-3β pathway and the activation of Nrf2 signaling pathway.

Objective: Predefining the most effective treatment for patients with depressive disorders remains a problem. We will examine the differential brain regions of gray matter (GM) in major depressive disorder (MDD) patients and the relationship between changes in their volume and the efficacy of early antidepressant treatment using magnetic resonance imaging (MRI). Methods: 159 never-medicated patients with first-episode MDD and 53 normal control subjects (NCs) were enrolled. The brains were scanned by MRI and measured with the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and after 2 weeks of treatment with selective serotonin reuptake inhibitor (SSRI)s, and the non-responder group and responder group were obtained. The patients were analyzed by voxel-based morphological (VBM) and SPSS software. Receiver operator characteristics (ROC) analysis was performed for the difference between the responder group and the non-responder group in the differential brain regions, and Pearson correlations were computed between volume size and HAMD score reduction rate. Results: Smaller GM volume of the right superior temporal gyrus (STG), and the orbital parts of the right medial frontal gyrus and right inferior frontal gyrus were observed in MDD versus the NCs. The non-responder group demonstrated a significant volume reduction at the right STG compared with the responders, but no corresponding change in orbital part of right medial frontal gyrus and right inferior frontal gyrus. ROC analysis showed that Accuracy=71.2%. There was a positive correlation between the STG gray matter volume and the HAMD-17 score reduction rate (r=0.347, p=0.002). Conclusion The study results confirmed the local changes in brain structure in MDD and may initially predict the early treatment response produced by SSRIs as antidepressants.

OBJECTIVE: Although the pathogenesis of depression remains unclear, C-reactive protein (CRP) levels are commonly elevated in depressed patients. Thus, CRP single-nucleotide polymorphisms (SNPs) that influence CRP levels may be associated with depression. In the present study, we explored whether CRP SNPs are related to depressive symptoms and antidepressants efficacy in Han Chinese patients.METHODS: We analyzed data from 440 patients with first-episode depression. We obtained genome CRP SNPs, scores of the 17-item Hamilton Rating Scale for Depression 17 (HAMD17) and its four-factor at baseline and after 6 weeks. Quantitative trait analysis was performed using UNPHASED software and curative effects were analyzed using SPSS software.RESULTS: Male patients with SNP rs1800947G exhibited lower insomnia scores and rs2794521CC exhibited lower scores of anxiety/ physical symptoms, total HAMD17 score. Female patients with rs2794521TT exhibited higher scores of insomnia and lower antidepressants efficacy.CONCLUSION: CRP SNPs rs1800947 and rs2794521 may be associated with depressive symptoms in patients with depression in a sex-specific fashion. Furthermore, rs2794521 may be a predictor of the efficacy of antidepressants in female patients.
Antidepressive Agents ; Asian Continental Ancestry Group ; C-Reactive Protein ; Depression ; Female ; Genome ; Humans ; Male ; Polymorphism, Single Nucleotide ; Sleep Initiation and Maintenance Disorders