AIM:To investigate the effect of paeoniflorin on the inflammatory response of diabetic retinopathy rats by regulating phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt)signaling pathway.METHODS: A total of 70 SPF male SD rats were selected, and 12 rats were randomly selected as the control group(normal saline gavage). The remaining 58 rats were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ)to establish diabetic rat models. Rats with diabetic retinopathy were randomly divided into model group(normal saline), paeoniflorin low-dose group(100 mg/kg paeoniflorin), paeoniflorin high-dose group(200 mg/kg paeoniflorin)and metformin group(100 mg/kg metformin), with 12 rats in each group. The body mass of the rats in each group were compared. HE staining was used to observe the pathological changes of the rat retina. Automatic biochemical analyzer was used to detect the levels of fasting blood glucose, glycosylated hemoglobin, serum high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), total cholesterol and triglyceride in the rats. Enzyme-linked immunosorbent assay was used to detect the levels of serum superoxide dismutase(SOD), reactive oxygen species(ROS), malondialdehyde(MDA), glutathione peroxidase(GSH-PX), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)and interleukin-1β(IL-1β)in the rats. Western blot was used to detect the expressions of Occludin, p-PI3K, tight junction protein-1(ZO-1), p-Akt and VE-Cadherin in the rat retina.RESULTS: The expression levels of Occludin, ZO-1 and VE-cadherin in low-dose and high-dose paeoniflora groups were higher than those in the model group, while the expression levels of TNF-α, IL-6, IL-1β, p-PI3K and p-Akt in serum were lower than those in the model group. The high-dose group of paeoniflorin was significantly better than the low-dose group of paeoniflorin(all P<0.05).CONCLUSION: Paeoniflorin may reduce inflammatory response in diabetic retinopathy rats by inhibiting PI3K/Akt signaling pathway.

AIM:To investigate the effect of paeoniflorin on the inflammatory response of diabetic retinopathy rats by regulating phosphatidylinositol-3 kinase/protein kinase B(PI3K/Akt)signaling pathway.METHODS: A total of 70 SPF male SD rats were selected, and 12 rats were randomly selected as the control group(normal saline gavage). The remaining 58 rats were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ)to establish diabetic rat models. Rats with diabetic retinopathy were randomly divided into model group(normal saline), paeoniflorin low-dose group(100 mg/kg paeoniflorin), paeoniflorin high-dose group(200 mg/kg paeoniflorin)and metformin group(100 mg/kg metformin), with 12 rats in each group. The body mass of the rats in each group were compared. HE staining was used to observe the pathological changes of the rat retina. Automatic biochemical analyzer was used to detect the levels of fasting blood glucose, glycosylated hemoglobin, serum high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), total cholesterol and triglyceride in the rats. Enzyme-linked immunosorbent assay was used to detect the levels of serum superoxide dismutase(SOD), reactive oxygen species(ROS), malondialdehyde(MDA), glutathione peroxidase(GSH-PX), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6)and interleukin-1β(IL-1β)in the rats. Western blot was used to detect the expressions of Occludin, p-PI3K, tight junction protein-1(ZO-1), p-Akt and VE-Cadherin in the rat retina.RESULTS: The expression levels of Occludin, ZO-1 and VE-cadherin in low-dose and high-dose paeoniflora groups were higher than those in the model group, while the expression levels of TNF-α, IL-6, IL-1β, p-PI3K and p-Akt in serum were lower than those in the model group. The high-dose group of paeoniflorin was significantly better than the low-dose group of paeoniflorin(all P<0.05).CONCLUSION: Paeoniflorin may reduce inflammatory response in diabetic retinopathy rats by inhibiting PI3K/Akt signaling pathway.

ObjectiveTo explore the role and mechanism of Hei Xiaoyaosan in regulating the protein kinase B （Akt）/glycogen synthase kinase-3β （GSK-3β）/nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway in cascade modulation of oxidative stress and apoptosis for preventing and treating Alzheimer's disease （AD）. MethodsNinety male SD rats of 4 months old were randomly assigned into a control group （n=10）， a sham group （with injection of 1 μL normal saline into bilateral hippocampi， n=10）， and a modeling group （with injection of 1 μL beta-amyloid 1-42 solution into bilateral hippocampi to induce AD， n=70）. One week after modeling， 50 successfully modeled rats were selected and randomly allocated into model， donepezil hydrochloride （0.45 mg·kg^-1）， and high-， medium-， and low-dose （15.30， 7.65， 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups. The rats were administrated with corresponding drugs once daily for six consecutive weeks. The Morris water maze was used to assess the learning and memory abilities of rats. Hematoxylin-eosin （HE） staining was performed to reveal hippocampal morphological changes in AD rats. Apoptosis in the hippocampal CA3 region was detected by terminal-deoxynucleotidyl transferase-mediated Nick end labeling. Immunofluorescence was used to visualize the expression of neuronal nuclear antigen （NeuN） in the CA1 region. Additionally， enzyme-linked immunosorbent assay was performed to assess the activities of glutathione peroxidase （GSH-Px）， glutathione-S-transferase （GST）， and catalase （CAT） in the hippocampus. Real-time PCR was conducted to measure the mRNA levels of Akt， GSK-3β， Nrf2， and HO-1， while Western blot was employed to determine the protein levels of phosphorylated Akt （p-Akt）/Akt， phosphorylated GSK-3β （p-GSK-3β）/GSK-3β， Nrf2， and HO-1. ResultsCompared with the control group， the model group on day 5 showed an increase in total swimming distance （P<0.01）， a reduction in the percentage of time spent in the target quadrant （P<0.01）， reduced and disarranged neurons， nuclear condensation， varying degrees of cellular damage， increased apoptosis of hippocampal neurons （P<0.01）， decreased NeuN content （P<0.01）， weakend activities of GSH-Px， GST， and CAT （P<0.01）， and down-regulated mRNA levels of Nrf2 and HO-1 （P<0.01） and protein levels of p-Akt/Akt， p-GSK-3β/GSK-3β， Nrf2， and HO-1 （P<0.01） in the hippocampus. Compared with the model group， donepezil hydrochloride and high， medium， and low doses of Hei Xiaoyaosan shortened the total swimming distance on day 5 （P<0.05， P<0.01）， increased the percentage of time spent in the target quadrant （P<0.05， P<0.01）， improved the arrangement and morphology of neurons， reduced nuclear condensation and the apoptosis rate of hippocampal neurons （P<0.01）， increased the NeuN content （P<0.01）， enhanced the activities of GSH-Px， GST， and CAT （P<0.05， P<0.01）， and up-regulated the mRNA levels of Nrf2 and HO-1 （P<0.05， P<0.01） and the protein levels of p-Akt/Akt， p-GSK-3β/GSK-3β， Nrf2， and HO-1 （P<0.05， P<0.01） in the hippocampus. ConclusionHei Xiaoyaosan can regulate the Akt/GSK-3β/Nrf2/HO-1 pathway to enhance the antioxidant stress capacity and inhibit neuron apoptosis to exert the neuroprotective effect， thereby ameliorating the cognitive dysfunction and pathological damage in AD rats.

ObjectiveTo explore the mechanism of Hei Xiaoyaosan in improving the cognitive function in Alzheimer's disease （AD） from cell apoptosis mediated by the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/nuclear factor kappa B （NF-κB） signaling pathway. MethodsFour-month-old SD male rats were randomly assigned into a blank group， a sham group， a model group， a donepezil hydrochloride （0.45 mg·kg^-1） group， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 10 rats in each group. The sham group received bilateral hippocampal injection of 1 μL normal saline， while the other groups received bilateral hippocampal injection of 1 μL beta-amyloid 1-42 （Aβ_1-42） solution for the modeling of AD. Rats were administrated with corresponding agents once a day for 42 consecutive days. The Morris water maze test was carried out to assess the learning and memory abilities of rats. Hematoxylin-eosin staining was employed to observe pathological changes in the hippocampus of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Western blot was employed to determine the protein levels of PI3K， Akt， and NF-κB. A cell model of AD was established by co-culturing Aβ_1-42 and PC12 cells in vitro. Cell viability and apoptosis were detected by the cell-counting kit 8 （CCK-8） assay and flow cytometry （FC）， respectively. ResultsAnimal experiments showed that compared with the blank group， the model group had a prolonged escape latency （P<0.01）， a reduced number of crossing platforms （P<0.01）， disarrangement and a reduced number of hippocampal neurons， up-regulated expression of Bax and Caspase-3， down-regulated expression of Bcl-2 （P<0.01）， decreased p-PI3K/PI3K and p-Akt/Akt levels， and an increased p-NF-κB/NF-κB level （P<0.01）. Compared with the model group， donepezil hydrochloride and high- and medium-dose Hei Xiaoyaosan shortened the escape latency and increased the number of crossing platforms （P<0.05， P<0.01）， improved the arrangement and increased the number of hippocampal neurons， down-regulated the expression levels of Bax and Caspase-3， up-reguated the expression level of Bcl-2 （P<0.05， P<0.01）， increased the p-PI3K/PI3K and p-Akt/Akt levels （P<0.05， P<0.01）， and reduced the p-NF-κB/NF-κB level （P<0.05， P<0.01）. Cell experiments showed that compared with the blank group， the model group exhibited an increased apoptosis rate （P<0.01）. Compared with the model group， the serum containing Hei Xiaoyaosan at various doses improved the cell viability （P<0.01）， and the serum containing Hei Xiaoyaosan at the high dose decreased the cell apoptosis （P<0.01）. ConclusionHei Xiaoyaosan may improve the learning and memory abilities of AD model rats by regulating cell apoptosis， while increasing the vitality and reducing the apoptosis rate of AD model cells via the PI3K/Akt/NF-κB signaling pathway.

ObjectiveTo investigate the effects of Hei Xiaoyaosan on cognitive impairment and the histone deacetylase sirtuin-1 （SIRT1）/tumor suppressor p53/solute carrier family 7 member 11 （SLC7A11） signaling pathway in the rat model of Alzheimer's disease （AD）. MethodsA total of 90 16-week-old SPF-grade SD male rats were randomly assigned in a blank group （n=10）， a sham group （n=10， with injection of 1 μL normal saline into the bilateral hippocampi）， and an AD modeling group （n=70， with injection of 1 μL β amyloid 1-42 solution into the bilateral hippocampi）. According to the random number table method， fifty successfully modeled rats were assigned into model， donepezil hydrochloride （0.45 mg·kg^-1）， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups， and they were administrated with corresponding agents via gavage once a day for 42 consecutive days. Morris water maze test was carried out to examine the cognitive function of rats. Nissl staining was employed to observe the morphology of hippocampal neurons in each group， and Prussian blue staining was used to detect iron deposition in the hippocampal tissue. Biochemical kits were used to measure the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and iron ion （Fe²⁺） in the hippocampal tissue. Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to determine the protein and mRNA levels， respectively， of SIRT1， p53， SLC7A11， glutathione peroxidase 4 （GPX4）， and acyl-CoA synthetase long-chain family member 4 （ACSL4） in the hippocampus. ResultsCompared with the blank group， the model group showed reductions in target quadrant movement distance （P<0.01） and target quadrant residence time （P<0.05）， disarrangement of hippocampal neurons， increased ferroptosis deposition in the hippocampus， a lowered level of SOD， risen levels of MDA and Fe²⁺ （P<0.05， P<0.01）， down-regulated protein and mRNA levels of SIRT1， SLC7A11， and GPX4 （P<0.05， P<0.01）， up-regulated protein and mRNA levels of p53 and ACSL4 （P<0.01）， and aggravated pathological process of AD. Compared with the model group， donepezil hydrochloride extended the target quadrant residence time and the target quadrant movement distance （P<0.05， P<0.01）. High- and medium- doses of Hei Xiaoyaosan extended the target quadrant residence time and the target quadrant movement distance （P<0.05， P<0.01）， improved the neuron arrangement and reduced the ferroptosis deposition in the hippocampus， elevated the SOD level， lowered the MDA and Fe²⁺ levels （P<0.05， P<0.01）， up-regulated the protein and mRNA levels of SIRT1， SLC7A11， and GPX4 （P<0.01， P<0.05）， and down-regulated the protein and mRNA levels of p53 and ACSL4 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan can regulate the SIRT1/p53/SLC7A11 signaling pathway to mitigate oxidative stress and inhibit ferroptosis， thereby ameliorating the cognitive dysfunction in AD rats.

ObjectiveTo explore the effect and mechanism of Hei Xiaoyaosan in regulating the tumor necrosis factor receptor superfamily member 6 （Fas）/Fas ligand （FasL）/cysteine protease-8 （Caspase-8）/cysteine protease-3 （Caspase-3） signaling pathway to intervene in neuronal apoptosis and prevent Alzheimer's disease （AD）. MethodNinety SPF-grade SD male rats of 4 months old were selected and randomly grouped as follows： 10 rats in the blank group， 10 rats in the sham group （bilateral hippocampus injected with 1 μL normal saline）， and 70 rats in the modeling group ［bilater hippocampus injected with 1 μL amyloid-beta protein 1-42 （Aβ_1-42） solution for the modeling of AD］. Fifty successfully modeled rats were selected and randomly assigned into model， donepezil hydrochloride （0.45 mg·kg^-1）， and high-， medium-， and low-dose （15.30， 7.65， 3.82 g·kg^-1） Hei Xiaoyaosan groups. Rats were administrated with corresponding agents by gavage once a day for 42 days. Terminal-deoxynucleoitidyl transferase-mediated nick end labeling （TUNEL） was employed to observe the apoptosis of neurons in the cortex and hippocampus， and immunohistochemistry （IHC） was used to detect the expression of B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax） in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to determine the mRNA levels of Fas， FasL， and Fas-associated protein with death domain （Fadd）. Western blot was used to determine the protein levels of Fas， FasL， Fadd， Caspase-3， cleved Caspase-3， Caspase-8， and cleved Caspase-8. ResultCompared with the blank group and sham group， the model group showed increased apoptosis rate in the cortex and hippocampus （P<0.01）， elevated Bax level （P<0.01）， lowered Bcl-2 level （P<0.01）， up-regulated mRNA levels of Fas， FasL， and Fadd in the hippocampus （P<0.01）， and up-regulated protein levels of Fas， FasL， Fadd， cleaved Caspase-3， and cleaved Caspase-8 （P<0.01）. Compared with the model group， donepezil hydrochloride and Hei Xiaoyaosan at high and medium doses decreased the apoptosis rate in the cortex and hippocampus （P<0.05， P<0.01）， lowered the Bax level （P<0.01）， elevated the Bcl-2 level （P<0.01）， and down-regulated the mRNA levels of Fas， FasL， and Fadd and the protein levels of Fas， FasL， Fadd， cleaved Caspase-3， and cleaved Caspase-8 （P<0.05， P<0.01） in the hippocampus. Low-dose Hei Xiaoyaosan decreased the apoptosis rate in the cortex and hippocampus （P<0.05， P<0.01）， lowered the Bcl-2 level （P<0.01）， and down-regulated the mRNA levels of FasL and Fadd （P<0.05） and the protein levels of Fas， FasL， Fadd， cleaved Caspase-3， and cleaved Caspase-8 （P<0.05） in the hippocampus. ConclusionHei Xiaoyaosan can protect neurons in the cortex and hippocampus of AD rats by inhibiting the apoptosis mediated by the Fas/FasL/Caspase-8/Caspase-3 signaling pathway.

ObjectiveTo explore the effect and mechanism of Hei Xiaoyaosan in modulating the synaptic plasticity in APP/PS1 mice by regulating the cyclic adenosine monophosphate （cAMP）/protein kinase A （PKA）/N-methyl-D-aspartate receptor （NMDAR） signaling pathway. MethodTwelve 4-month-old male C57BL/6J mice were selected as the blank control group， and 60 4-month-old male APP/PS1 double transgenic mice were randomized into model， KW-6002 （adenosine receptor antagonist， 3 mg·kg^-1）， and high-， medium-， and low-dose （22.10， 11.05， 5.53 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 12 mice in each group. Mice were administrated with corresponding drugs for 90 days. Transmission electron microscopy was employed to observe the synaptic ultrastructure of hippocampal neurons， and Golgi staining was used to observe the dendritic spine density of neurons in hippocampal CA1 region. Western blot was employed to measure the protein levels of cAMP， PKA， N-methyl-D-aspartate receptors 1， 2A， and 2B （NR1， NR2A， and NR2B， respectively）， postsynaptic density protein 95 （PSD95）， and synapsin 1 （SYN1）. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to determine the mRNA levels of cAMP， PKA， and NR1. Enzyme-linked immunosorbent assay was employed to determine the content of interleukin-12 （IL-12） and interleukin-4 （IL-4） in the hippocampus. ResultCompared with the blank group， the model group showed blurred boundaries between presynaptic membrane and postsynaptic membrane in hippocampal CA1 region， reduced and scattered synaptic vesicles， and decreased density of postsynaptic membrane， and irregular， disarranged， and loosened dendritic spines of neurons in hippocampal CA1 region （P<0.01）. In addition， the model group presented down-regulated protein levels of cAMP， PKA， NR1， NR2A， NR2B， PSD95， and SYN1 and mRNA levels of cAMP， PKA， and NR1， elevated IL-12 level， and lowered IL-4 level in the hippocampus （P<0.01）. Compared with the model group， the drug intervention groups showed clear and intact boundaries between presynaptic membrane and postsynaptic membrane in hippocampal CA1 region， increased synaptic vesicles with dense arrangement， increased density of postsynaptic membrane， and improved morphology， arrangement， and density of neuronal dendritic spines （P<0.05， P<0.01）. In addition， the drug interventions up-regulated the protein levels of cAMP， PKA， NR1， NR2A， NR2B， PSD95， and SYN1 （P<0.05，P<0.01） and mRNA levels of cAMP， PKA， and NR1 （P<0.01）， lowered the IL-12 level （P<0.01）， and elevated the IL-4 level （P<0.01） in the hippocampus. ConclusionHei Xiaoyaosan can improve the structure and morphology of hippocampal neurons in APP/PS1 mice by activating the cAMP/PKA/NMDAR signaling pathway and repairing synaptic plasticity.

ObjectiveTo investigate the role and mechanism of Hei Xiaoyaosan in intervening in oxidative stress in the rat model of Alzheimer's disease （AD） via modulating the rat sarcoma （RAS）/rapidly accelerating fibrosarcoma （RAF）/mitogen-activated protein kinase kinase （MEK）/extracellular signal-regulated kinase （ERK） signaling pathway. MethodOne hundred 4-month-old SPF-grade Wistar male rats were randomly grouped as follows： 10 in the blank group， 10 in the sham group （bilateral hippocampus injected with 1 μL normal saline）， and 80 in the modeling group ［bilateral hippocampus injected with 1 μL amyloid beta protein 1-42 （Aβ_1-42） solution for the modeling of AD］. Fifty rats qualified for modeling were selected and randomized into the model， donepezil hydrochloride （0.5 mg·kg^-1）， and high-， medium-， and low-dose （15.30， 7.65， 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups. The rats were administrated with corresponding drugs by gavage once a day for 42 consecutive days. At the end of gavage， Morris water maze test was performed to examine the learning and memory abilities of the rats， and Nissl staining was used to observe the pathological changes of neurons in CA3 region of the hippocampus. The immunofluorescence assay was used to observe Aβ deposition and tau phosphorylation. Western blot was employed to determine the protein levels of RAS， RAF， phosphorylated （p）-RAF， MEK， p-MEK， ERK， and p-ERK in the hippocampal tissue. Biochemical methods were used to determine the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， and superoxide dismutase （SOD） in the hippocampal tissue. ResultCompared with the sham group， the model group showed prolonged escape latency （P<0.01）， shortened swimming distance in the target quadrant （P<0.01）， reduced and uneven stained Nissl bodies， enhanced fluorescence intensity of Aβ and p-tau （P<0.01）， up-regulated protein levels of RAS， p-RAF， p-MEK， and p-ERK in the hippocampal tissue （P<0.01）， increased ROS and MDA content （P<0.01）， and decreased SOD activity （P<0.01） on day 5. Compared with the model group， donepezil hydrochloride and high-， medium-， and low-dose Hei Xiaoyaosan shortened the escape latency （P<0.01）， increased the swimming distance in the target quadrant （P<0.01）， improved the arrangement， morphology， and structures of neurons and the number and distribution of Nissl bodies， decreased the fluorescence intensity of Aβ and p-tau （P<0.01）， up-regulated the protein levels of RAS， p-RAF， p-MEK， and p-ERK （P<0.05， P<0.01）， decreased the ROS and MDA content （P<0.01）， and increased the SOD activity （P<0.01） on day 5. ConclusionHei Xiaoyaosan may ameliorate oxidative stress， reduce Aβ and p-tau levels， and inhibit hippocampal neuronal damage by regulating the RAS/RAF/MEK/ERK signaling pathway， thus improving learning and memory abilities.

Alzheimer's disease （AD） is a neurodegenerative disease that predominantly affects the elderly. It belongs to the category of dementia in traditional Chinese medicine （TCM）， with the onset and progression closely associated with the functions of the kidney， liver， and spleen. The classic TCM formula Hei Xiaoyaosan， which regulates the three Yin of liver， spleen， and kidney， shows broad prospects in treating neurodegenerative diseases. This article reviews the experimental studies reported in the past decade to summarize the mechanisms of Hei Xiaoyaosan and its active components in intervening in AD. Hei Xiaoyaosan can treat AD via multiple targets， levels， and aspects comprehensively. The clinical studies have demonstrated that Hei Xiaoyaosan alone or in combination with other therapies has a definite therapeutic effect on AD. Specifically， it can ameliorate the cognitive impairment， mitigate oxidative stress， and inhibit the overexpression of soluble apoptotic factors in AD patients. This review aims to provide a theoretical basis for the treatment of AD with Hei Xiaoyaosan and explore new research directions. Moreover， it gives new insights into the clinical application of Hei Xiaoyaosan and the development of products with both medicinal and edible values.

AIM: To investigate the efficacy and safety of ZKY001 eye drops with different concentrations in the treatment of corneal epithelial defects(CED)after primary pterygium excision.METHODS: This was a multicenter, randomized, double-blinded, placebo-controlled phase II clinical trial. From March 15, 2022 to November 14, 2022, patients with primary pterygium who had undergone surgery were recruited from 12 tertiary hospitals across China. Using block randomization, 178 patients(178 eyes)were randomly assigned to 3 groups in a 1:1:1 ratio: 0.002% ZKY001 group(n=59), 0.004% ZKY001 group(n=59), and placebo group(n=60, receiving ZKY001 sham eye drops). Subjects in each group received 1 drop of the study drug 4 times per day for 4 d. The percentage of CED area recovery from baseline, the first complete healing time of CED area, the number of first complete healing cases of CED, and changes in visual analogue scale(VAS)scores for eye discomfort including eye pain, foreign body sensation, tearing and photophobia were observed.RESULTS: In terms of improvement in CED, there were no statistically significant differences among the three groups including the first healing time of CED, the percentage improvement in CED area compared to baseline, and the percentage of first healing cases at different follow-up visits(all P>0.05). Numerically, the first healing time of CED was shorter in the test groups compared to the placebo group(67.87±21.688 h for the 0.002% ZKY001 group, 61.48±22.091 h for the 0.004% ZKY001 group, and 68.85±20.851 h for the placebo group). On D1 morning, the percentage improvement in CED area compared to baseline was maximally different from the placebo group, and the numerical difference advantage was maintained at subsequent follow-up visits. The number of first healing cases in the CED area at different follow-up visits was higher in the test groups than the placebo group. In terms of improvement in ocular discomfort, the total VAS scores were lower in the test groups compared to the placebo group, mainly due to reductions in foreign body sensation and pain scores. At D3, the 0.004% ZKY001 group showed statistically significant improvement in foreign body sensation(P<0.017). In terms of safety, the overall incidence of adverse events was low(9.0%)and similar among groups.CONCLUSION: The use of ZKY001 eyedrops after primary pterygium surgery can safely improve the CED repair, and alleviate postoperative symptoms caused by CED.