ObjectiveTo investigate whether Shixiaosan can improve neurological function and inhibit ferroptosis in rats with cerebral ischemia-reperfusion injury （CIRI） by regulating the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） pathway. MethodsA rat model of CIRI was established using the intraluminal filament method. Briefly， cervical blood vessels were separated， branches of the external carotid artery were ligated， and the common carotid artery and internal carotid artery were clamped. A nylon filament was inserted through the opening of the external carotid artery to the origin of the middle cerebral artery to block blood flow and induce cerebral ischemia. After 60-120 min of ischemia， the filament was withdrawn to restore blood flow， and the external carotid artery incision was ligated. The rats were divided into a CIRI group， a Shixiaosan low-dose （-L） group （intragastric administration of 1.26 g·kg^-1 Shixiaosan）， a Shixiaosan high-dose （-H） group （intragastric administration of 2.52 g·kg^-1 Shixiaosan）， a donepezil hydrochloride tablet （DON） group （intragastric administration of 0.45 mg·kg^-1 DON）， and a Shixiaosan -H + Nrf2 inhibitor （ML385） group （intragastric administration of 2.52 g·kg^-1 Shixiaosan combined with intraperitoneal injection of 30 mg·kg^-1 ML385）. An additional 12 rats underwent cervical artery separation followed by incision suturing and served as the control group. Equal volumes of double-distilled water were administered to the CIRI and control groups. Neurological function impairment was assessed using the modified Garcia JH score. Magnetic resonance imaging was used to determine the cerebral infarct volume ratio. Hematoxylin-eosin （HE） staining and Prussian blue staining were performed to observe neuronal injury and iron accumulation in the ischemic penumbra， respectively. Transmission electron microscopy was used to examine the ultrastructure of neuronal mitochondria in the ischemic penumbra. Commercial kits were used to measure ferrous iron （Fe²⁺）， malondialdehyde （MDA）， reduced glutathione （GSH） content， and reactive oxygen species （ROS） activity in the ischemic penumbra. The BODIPY （581/591） C11 fluorescent probe was used to detect intracellular lipid peroxidation levels. Western blot was performed to detect protein expression levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFRC）， ferritin heavy chain （FHC）， and ferritin light chain （FLC） in the ischemic penumbra. ResultsCompared with the control group， the CIRI group exhibited neuronal injury in the ischemic penumbra， characterized by reduced neuron numbers， nucleolar shrinkage， and interstitial edema. Marked iron accumulation was observed in the tissue. Neuronal mitochondria showed atrophy and rupture， with reduced mitochondrial cristae and increased membrane density. The cerebral infarct volume ratio， Fe²⁺ content， MDA content， ROS activity， and lipid peroxidation levels were increased， whereas the modified Garcia JH score， GSH content， and protein expression levels of Nrf2， SLC7A11， GPX4， FHC， and FLC were decreased， and TFRC protein expression was increased （P<0.05）. Compared with the CIRI group， the Shixiaosan -L group， Shixiaosan -H group， and DON group showed attenuated neuronal injury in the ischemic penumbra， reduced iron accumulation， alleviated mitochondrial damage， decreased cerebral infarct volume ratio， Fe²⁺ and MDA contents， ROS activity， and lipid peroxidation levels， as well as increased modified Garcia JH scores， GSH content， and protein expression levels of Nrf2， SLC7A11， GPX4， FHC， and FLC， while TFRC protein expression was decreased （P<0.05）. The magnitude of changes in all indicators was greater in the Shixiaosan -H group than in the Shixiaosan -L group （P<0.05）. Compared with the Shixiaosan -H group， all measured indicators in the Shixiaosan -H + ML385 group showed opposite trends （P<0.05）. ConclusionShixiaosan may inhibit ferroptosis and restore neurological function in rats with CIRI by activating the Nrf2/SLC7A11/GPX4 pathway.

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Purpose: Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels. Materials and Methods: A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro. Results: Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect. Conclusion Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.

Objectives: . This study aimed to explore the role of the Pcdh15 gene in hearing maintenance and to examine the effects of its deficiency on cochlear structure, cochlear function, and hearing loss in mice. Methods: . CRISPR/Cas9 technology was used to generate Pcdh15 knockout (KO) mice. Auditory function was evaluated using hearing tests, while histological approaches were employed to assess morphological changes in cochlear hair cells and spiral ganglion neurons (SGNs). RNA sequencing (RNA-seq) was performed on cochlear tissue from postnatal day 18 (P18) wild-type (WT) and Pcdh15 KO mice to identify differentially expressed genes (DEGs). These DEGs were subjected to functional annotation and pathway analysis, with particular emphasis on oxidative phosphorylation (OXPHOS). Reactive oxygen species (ROS) levels were quantified using flow cytometry and DCFH-DA assays. Results: . Pcdh15 KO mice exhibited progressive sensorineural hearing loss, which worsened to profound deafness by P18. Notably, cochlear hair cells and SGNs showed substantial loss and pronounced morphological abnormalities, particularly within the basal high-frequency region. RNA-seq analysis identified 1,359 DEGs, including 1,024 downregulated and 335 upregulated genes. Pathway analysis indicated that Pcdh15 deficiency was associated with inhibition of the OXPHOS pathway, potentially disrupting mitochondrial respiratory chain complexes I, III, IV, and V and thereby impairing energy production and ATP metabolism. In addition, early-stage cochleae from KO mice demonstrated elevated ROS levels and increased oxidative stress, suggesting that redox imbalance may contribute to hearing damage. Conclusion . Pcdh15 plays a critical role in hearing maintenance. Its deficiency is associated with severe hearing loss and marked cochlear abnormalities, which are linked to inhibition of OXPHOS, disruption of energy metabolism, and exacerbation of oxidative stress. Together, these findings provide new insights into the mechanisms underlying hearing loss and suggest potential targets for therapeutic intervention.

Objective To investigate the current status of work readiness and its influencing factors among patients returning to work after lung cancer surgery. Methods A retrospective study was conducted on young and middle-aged postoperative lung cancer patients who were treated at the Department of Thoracic Surgery, West China Hospital, Sichuan University from March to September 2023 and returned to their jobs. Data were collected through a general information questionnaire, readiness for return-to-work scale (RRTW), general self-efficacy scale (GSES), and simplified coping style questionnaire (SCSQ). Univariate and multivariate logistic regression analyses were used to explore the factors affecting the work readiness of patients returning to work. Results A total of 219 patients were included, with 59 males and 160 females aged 18-60 years. Among the postoperative lung cancer patients returning to work, 73.1% were in the active maintenance stage of return-to-work readiness with a RRTW score of (17.59±1.48) points, and 26.9% were in the uncertain maintenance stage with a RRTW score of (16.22±1.50) points. Multivariate logistic regression analysis showed that patients aged≤30 years (OR=52.381), employees of enterprises and institutions (OR=7.682), agricultural, pastoral, fishery, forestry laborers (OR=15.665), positive coping (OR=5.043), those with higher self-efficacy (OR=1.157) and engaged in physically demanding work (OR=2.449) had higher return-to-work readiness, while patients with≥2 children (OR=0.055), self-payment (OR=0.044), and those working more than 40 hours per week (OR=0.122) had lower return-to-work readiness. Conclusion The return-to-work readiness of young and middle-aged postoperative lung cancer patients needs to be improved, and occupation, job nature, main coping styles, general self-efficacy and other factors are associated with return-to-work readiness.

ObjectiveTo investigate the association of hepatic steatosis with the level of viral replication and the progression of hepatic fibrosis in patients with chronic hepatitis B （CHB） through a real-world study， and to determine the independent influencing factors for hepatic fibrosis. MethodsA total of 887 CHB patients who attended the outpatient service and inpatient ward of Hepatology in The First Affiliated Hospital of Dalian Medical University from July 2021 to March 2025 were enrolled as subjects， and according to the presence or absence of metabolic dysfunction-associated steatotic liver disease （MASLD）， they were divided into CHB group with 560 patients and CHB+MASLD group with 327 patients. The association between hepatic steatosis and HBV load in CHB patients was analyzed， as well as the impact of varying degrees of hepatic steatosis on hepatic fibrosis. The t-test or the Mann-Whitney U test was used for comparison of continuous data between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； a Spearman correlation analysis was performed； a Logistic regression analysis was used to investigate influencing factors. ResultsThe patients enrolled received antiviral therapy according to viral load； of all patients， 275 （31%） received nucleos（t）ide analogue combined with pegylated interferon-α， 532 （60%） received nucleos（t）ide analogue monotherapy， and 80 （9%） did not receive antiviral therapy. A total of 44 patients （5.0%） who were receiving PEG-IFN-α therapy and had marked thrombocytopenia were excluded， and finally 843 patients were included for comparison of aspartate aminotransferase-to-platelet ratio index （APRI） and fibrosis-4 index （FIB-4）. Compared with the CHB group， the CHB+MASLD group had a significantly higher proportion of male patients （χ²=5.917， P<0.05） and a significant increase in CAP value （t=21.646， P<0.05）. The median values of liver function parameters for the population enrolled were within the normal range， and no significant inflammatory activity was observed. The virological analysis showed that compared with the CHB group， the CHB+MASLD group had significantly lower serum level of pregenomic RNA （Z=-2.894， P<0.05） and HBeAg positivity rate （χ²=8.725， P<0.05）， and CAP was significantly negatively correlated with pgRNA （r=-0.117， P<0.05）. In the HBeAg-negative subgroup， compared with the CHB group， the CHB+MASLD group had a significantly lower level of hepatitis B surface antigen （Z=-0.765， P<0.05）； in the HBeAg-positive subgroup， the CHB+MASLD group had a significantly higher level of HBV DNA than the CHB group （Z=-2.509， P<0.05）. The analysis of hepatic fibrosis showed that the CHB+MASLD group had significantly lower values of APRI （Z=-3.418， P<0.05） and FIB-4 （Z=-6.237， P<0.05）. Compared with the CHB group， the CHB+MASLD S1 group had a significantly higher proportion of patients without fibrosis and a significantly lower proportion patients with liver cirrhosis （χ²=7.935， P<0.05）； in the CHB+MASLD S2 group， there was no significant difference in the proportion of patients with different fibrosis stages； the CHB+MASLD S3 group had a significantly lower proportion of patients without fibrosis and a significantly higher proportion of patients with early-stage fibrosis （χ²=9.101， P<0.05）. The Logistic regression analysis showed that an increase in CAP （odds ratio ［OR］=1.08， 95% confidence interval ［CI］： 1.03 — 1.13， P<0.05）， an increase in age （OR=1.02， 95%CI： 1.01 — 1.04， P<0.05）， male sex （OR=1.77， 95%CI： 1.19 — 2.64， P<0.05）， an increase in HBV DNA （OR=1.35， 95%CI： 1.15 — 1.57， P<0.001）， an increase in aspartate aminotransferase （OR=1.02， 95%CI： 1.01 — 1.03， P<0.001）， and an increase in gamma-glutamyl transpeptidase （OR=1.00， 95%CI： 1.00 — 1.01， P=0.028） were independent influencing factors for hepatic fibrosis. The risk of hepatic fibrosis in S3 patients was higher than that in patients without steatosis （OR=5.05， 95%CI： 2.48 — 10.29， P<0.001）. ConclusionThere is a lower level of HBV replication in CHB patients comorbid with MASLD. Hepatic steatosis is associated with HBV-related virological markers and the progression of hepatic fibrosis， and severe fatty liver disease may promote the progression of hepatic fibrosis in CHB patients.

Based on the modern understanding that lipid metabolism disorders mediate tumor microenvironmental imbalance in esophageal carcinoma， this paper proposes that failure of spleen and kidney warming and internal accumulation of phlegm-toxin constitute the core pathogenesis of esophageal carcinoma. Deficiency of spleen and kidney yang qi serves as the root cause， while impaired transformation and transportation of lipids and the accumulation of phlegm-toxin represent the superficial manifestations. Phlegm originates from the transformation of lipids， while toxin arises from and attaches to phlegm. Their interaction forms a sticky and persistent pathological state that runs throughout the entire disease process. The evolution of pathogenesis follows a dynamic and progressive pattern. In the early stage， failure of spleen and kidney warming and dysfunction of lipid metabolism mediate abnormalities in a lipid-enriched microenvironment； in the middle stage， lipid turbidity condenses into phlegm， and phlegm-toxin stasis promotes the formation of an inflammatory and hypercoagulable microenvironment； in the late stage， dysfunction of the sanjiao （三焦） warming function and impaired qi transformation lead to an imbalance in the hypoxic and metabolically dysfunctional microenvironment. Accordingly， a staged therapeutic approach is proposed， including warming the kidney and strengthening the spleen， transforming phlegm and resolving toxin， and warming and unblocking the sanjiao. By regulating lipid metabolism to restore tumor microenvironmental homeostasis， this approach provides a new theore-tical perspective and practical strategy for the intervention of esophageal cancer progression through traditional Chinese medicine.

Based on the modern understanding that lipid metabolism disorders mediate tumor microenvironmental imbalance in esophageal carcinoma， this paper proposes that failure of spleen and kidney warming and internal accumulation of phlegm-toxin constitute the core pathogenesis of esophageal carcinoma. Deficiency of spleen and kidney yang qi serves as the root cause， while impaired transformation and transportation of lipids and the accumulation of phlegm-toxin represent the superficial manifestations. Phlegm originates from the transformation of lipids， while toxin arises from and attaches to phlegm. Their interaction forms a sticky and persistent pathological state that runs throughout the entire disease process. The evolution of pathogenesis follows a dynamic and progressive pattern. In the early stage， failure of spleen and kidney warming and dysfunction of lipid metabolism mediate abnormalities in a lipid-enriched microenvironment； in the middle stage， lipid turbidity condenses into phlegm， and phlegm-toxin stasis promotes the formation of an inflammatory and hypercoagulable microenvironment； in the late stage， dysfunction of the sanjiao （三焦） warming function and impaired qi transformation lead to an imbalance in the hypoxic and metabolically dysfunctional microenvironment. Accordingly， a staged therapeutic approach is proposed， including warming the kidney and strengthening the spleen， transforming phlegm and resolving toxin， and warming and unblocking the sanjiao. By regulating lipid metabolism to restore tumor microenvironmental homeostasis， this approach provides a new theore-tical perspective and practical strategy for the intervention of esophageal cancer progression through traditional Chinese medicine.

Tissue repair requires the reconstruction of functional vascular networks to restore oxygen and nutrient delivery, eliminate metabolic waste, and maintain tissue homeostasis. Although biochemical factors such as growth factors and cytokines have been extensively studied in vascular regeneration, increasing evidence indicates that mechanical signals from the extracellular matrix (ECM) are equally important regulators of angiogenesis. Matrix stiffness, as a major biomechanical property of the tissue microenvironment, provides critical information that influences endothelial cell (EC) behavior and vascular remodeling through mechanotransduction. However, the biological effects of matrix stiffness are not universally defined as either pro- or anti-angiogenic, but are highly dependent on tissue context, cellular composition, disease progression, and the dynamic changes occurring during tissue repair. Therefore, understanding how matrix stiffness regulates vascular regeneration is essential for developing more precise strategies for tissue engineering and regenerative medicine. In this review, we summarize recent advances in the regulation of angiogenesis by matrix stiffness during tissue repair from multiple perspectives. First, we discuss the direct effects of matrix stiffness on EC behaviors, including differentiation, morphological remodeling, migration, proliferation, barrier maintenance, and vascular network formation. ECs sense mechanical alterations in the surrounding matrix through various mechanosensitive structures, including integrins, focal adhesion complexes, and mechanosensitive ion channels such as Piezo1 and TRPV proteins. These mechanical signals are subsequently transmitted through intracellular pathways involving FAK, RhoA/ROCK, MAPK, and Hippo-YAP/TAZ signaling, leading to cytoskeletal reorganization and transcriptional regulation. Through these mechanisms, matrix stiffness regulates endothelial functional states and determines the balance between regenerative vascular formation and pathological vascular remodeling. Beyond the direct regulation of ECs, we further highlight the importance of stiffness-mediated intercellular communication within the regenerative microenvironment. Matrix stiffness can regulate the behavior and secretory profiles of vascular-associated cells, including mesenchymal stem cells and macrophages, thereby indirectly affecting endothelial function through paracrine mechanisms. Changes in matrix mechanics influence the secretion of angiogenic factors, inflammatory cytokines, and extracellular vesicles from these cells, creating a mechanical regulation network that coordinates vascular regeneration. This perspective extends the traditional concept of matrix stiffness from a physical support structure to an active regulatory signal that integrates multiple cellular responses during tissue repair. Furthermore, we discuss the tissue-specific effects of matrix stiffness in vascular regeneration across different organs, including the aorta, lung, liver, and heart. Although excessive matrix stiffening is frequently associated with fibrosis and vascular dysfunction, the consequences of mechanical changes vary considerably among tissues. Moderate stiffness alterations may support endothelial activation and vascular stabilization in certain regenerative contexts, whereas persistent pathological stiffening can promote inflammation, endothelial dysfunction, and impaired vascular repair. These findings emphasize that the biological meaning of “soft” and “stiff” microenvironments should be interpreted according to specific tissue and experimental conditions rather than as universal mechanical classifications. Finally, we summarize current challenges and future perspectives in this field. A major limitation is the lack of standardized mechanical characterization among different studies, as stiffness measurements are influenced by material properties, testing methods, and experimental conditions, limiting direct comparison across research systems. Moreover, most existing models fail to fully reproduce the dynamic and viscoelastic properties of native ECM during tissue regeneration. Future studies should combine advanced biomaterials with standardized mechanical analysis, organoid models, and multi-omics approaches to establish more accurate mechanical regulatory maps. Overall, this review proposes that matrix stiffness is not merely a structural feature of tissues, but an active biological signal that regulates vascular regeneration through coordinated mechanotransduction and multicellular interactions. A deeper understanding of stiffness-mediated vascular regulation will provide new theoretical insights and therapeutic opportunities for improving tissue repair outcomes.

ObjectiveTo investigate the effects of Liuwei Dihuangwan on mammalian target of rapamycin （mTOR）-mediated synaptic plasticity in the prefrontal cortex-hippocampus circuit in the rat model of valproic acid （VPA）-induced autism spectrum disorder （ASD） and to explore its potential mechanism for reducing behavioral abnormalities in ASD rats. MethodsThirteen SD pregnant rats were randomized into the VPA group （10 rats） and the control group （3 rats）. On gestational day 13， the VPA group was intraperitoneally injected with VPA solution （600 mg·kg^-1）， while the control group was injected with an equal volume of normal saline. Male pups of 21 days old from both groups underwent behavioral tests to screen the ASD model rats （32 rats）. These rats were then randomly assigned to the model （distilled water）， vitamin D （1 480 U·kg^-1）， low-dose （0.75 g·kg^-1） Liuwei Dihuangwan， and high-dose （1.5 g·kg^-1） Liuwei Dihuangwan groups， and normal male pups were selected as the blank group （distilled water）， with 8 rats in each group. Each group was treated with the corresponding drug or an equal volume of distilled water via gavage daily. After drug administration， behavioral tests were conducted again， followed by anesthesia and tissue collection. Nissl staining was carried out to observe the morphological changes of neurons in the prefrontal cortex and hippocampus. Transmission electron microscopy was used to observe changes in hippocampal synaptic structure. Immunohistochemistry and Western blot were employed to determine the expression of mTOR， phosphatidylinositol 3-kinase （PI3K）， and protein kinase B （Akt） in the prefrontal cortex， as well as synaptophysin-1 （SYP-1）， postsynaptic density 95 （PSD95）， and N-methyl-D-aspartate receptors （NMDARs） in the hippocampus. ResultsCompared with the control group， the model group exhibited severe growth retardation and developmental deformities， with abnormal behavioral performance and pathological damage to neurons and synapses in the prefrontal cortex and hippocampus. Compared with the model group， all treatment groups showed reduced behavioral abnormalities and pathological damage to neurons and synapses in the prefrontal cortex and hippocampus， with the most significant effects in the high-dose Liuwei Dihuangwan group. Immunohistochemistry and Western blotting results showed that compared with the control group， the model group exhibited significantly increased protein levels and phosphorylation ratios of p-mTOR， p-Akt， and p-PI3K in the prefrontal cortex （P<0.05， P<0.01）， and decreased protein levels of SYP-1 and PSD95 and increased protein level of NMDARs in the hippocampus （P<0.01）. Compared with those in the model group， the protein levels of p-mTOR， p-Akt， and p-PI3K in the prefrontal cortex decreased in the vitamin D and high-dose Liuwei Dihuangwan groups （P<0.05）， and the p-mTOR/mTOR， p-Akt/Akt， and p-PI3K/PI3K ratios in the prefrontal cortex declined in the vitamin D group （P<0.05）. The high-dose Liuwei Dihuangwan group showed a reduction in p-PI3K/PI3K ratio （P<0.05）. The protein level of SYP-1 and PSD95 in the hippocampus increased in the vitamin D， low-dose Liuwei Dihuangwan， and high-dose Liuwei Dihuangwan groups （P<0.05， P<0.01）， while the protein level of NMDARs decreased in the vitamin D and high-dose Liuwei Dihuangwan groups （P<0.01）. ConclusionLiuwei Dihuangwan significantly reduces VPA-induced ASD-like behaviors and enhances the regeneration and repair of neurons in the prefrontal cortex and synaptic structures in the hippocampus by downregulating of PI3K/Akt/mTOR expression in the prefrontal cortex， upregulating SYP-1 and PSD95 expression in the hippocampus， and inhibiting NMDARs expression.