Bronchopulmonary dysplasia (BPD) is a prevalent chronic lung disease in extremely preterm infants, characterized by arrested alveolarization and pulmonary vascular impairment. In neonatal mice and A549 cells, hyperoxia exposure significantly downregulated SIRT3 expression and PDH activity, resulting in severe mitochondrial structural and functional damage. Quantitative acetylome analysis revealed this deficiency leads to the hyperacetylation of PDHA1 at lysine 83. This modification inhibits PDH activity, forcing a pathogenic metabolic shift toward lactate accumulation and mitochondrial dysfunction. In vitro, a deacetylation-mimetic PDHA1-K83R mutant restored PDH activity and mitigated hyperoxia-induced mitochondrial injury. In vivo, pharmacological activation of SIRT3 with Honokiol prevented PDHA1 hyperacetylation, preserved mitochondrial function, and alleviated alveolar simplification. PDHA1 hyperacetylation at K83 is an important downstream event associated with SIRT3 deficiency and contributes to mitochondrial and metabolic dysfunction in hyperoxia-induced BPD. Targeting the SIRT3/PDHA1 axis provides a promising metabolic intervention strategy for BPD treatment.

Overcoming therapeutic resistance mediated by apoptosis evasion represents a critical challenge in cancer treatment. Pyroptosis, an inflammatory form of regulated cell death, provides a promising alternative approach capable of stimulating robust anti-tumor immunity and converting immunologically inert ("cold") tumors into immunologically active ("hot") microenvironments. Importantly, these cell death pathways are not isolated but are interconnected through dynamic molecular switches that determine cellular fate. This review systematically examines the intricate molecular crosstalk between cell death modalities, with particular emphasis on the regulatory roles of the caspase-3/GSDME and caspase-8/GSDMD axes. Current evidence demonstrates that caspase family members, primarily associated with apoptosis, can selectively cleave gasdermin proteins, facilitating a transition from non-inflammatory apoptotic signaling to inflammatory pyroptotic events. We further analyze how inflammasomes, post-translational modifications, and the STING-NF-κB pathway precisely regulate this transition. Through integrated bioinformatic analysis, we identified novel hub genes (e.g., PRKAR1A, PPP2CA, FOSL2) and microRNA networks at the apoptosis-pyroptosis interface, providing novel insights and potential therapeutic targets. Exploiting this 'death switch' offers a novel therapeutic framework through three principal strategies: (1) inducing pyroptosis to eliminate apoptosis-resistant cells, (2) utilizing pyroptosis-induced inflammation to enhance immune checkpoint inhibitor efficacy, and (3) developing targeted therapeutics that directly modulate these switch molecules. Although controlling pyroptosis-associated inflammation remains challenging, understanding and manipulating the apoptosis-to-pyroptosis transition provides an innovative approach to overcome drug resistance and develop more effective cancer treatments.

BackgroundLeft ventricular non-compaction (LVNC) is a rare type of cardiomyopathy. It is more difficult to diagnose during the neonatal period. This study reported the clinical manifestations of neonatal LVNC at initial diagnosis and investigated their short-term outcomes.MethodsA cohort of 10 neonates was enrolled. Their clinical characteristics were analyzed, and follow-up was conducted for 1 year.ResultsThe neonates had an average gestational age of 35.82 weeks and an average birth weight of 2,636 g. The average age at initial diagnosis was 12 days and clinical manifestations were highly variable, ranging from asymptomatic (20%) to cyanosis (50%), dyspnea (50%), arrhythmia (60%), and heart failure (30%). Plasma myocardial injury markers were elevated, and electrocardiogram abnormalities were present in 90% of infants. Echocardiography revealed an average left ventricular (LV) non-compacted/compacted ratio of 2.96 and reduced systolic function (ejection fraction: 38.5%; fractional shortening: 18.8%). The average LV internal diameters were both above the normative reference intervals, with an end-diastolic diameter of 2.26 cm and an end-systolic diameter of 1.84 cm. During follow-up, two neonates died. Among the eight survivors, three with non-isolated LVNC underwent cardiac surgery, whereas five were asymptomatic with normal LV systolic function at 1 year of age.ConclusionsThe clinical presentation of neonatal LVNC varies widely, from asymptomatic to those with dyspnea, cyanosis, arrhythmia, or heart failure. In our cohort, heart failure at initial diagnosis was associated with a poorer prognosis. Short-term follow-up suggested that with aggressive management, myocardial function may show signs of reversibility in a subset of neonates.

Multidrug resistance (MDR) is one of the major problems in cancer treatment. Overcoming MDR to achieve effective cancer treatment remains a huge challenge. Here, we proposed a self-generative singlet oxygen (1O2)-initiated chemical modification of nuclear DNAs (SiCMoND) approach to kill multidrug-resistant tumor synergizing with chemotherapy. A tumor-targeted "nano-bomb" FA(CT-fT-Dox) was rationally fabricated by encapsulating the complex of Cu2+ with tetrakis(4-carboxyphenyl) porphyrin) (Cu-TCPP) as a 1O2 generator and a doxorubicin (Dox) prodrug tailed with a furan-containing positively charged peptide (fTAT-Dox) within the micelles of FA-PEG5000-PCL3000 and mPEG5000-PCL3000. When FA(CT-fT-Dox) nanoparticles accumulated at the tumor site, they could undergo disassembly in the tumor microenvironment (TME) specifically to release Cu-TCPP and fTAT-Dox simultaneously. Taking advantage of the features of Cu-TCPP that can convert tumor-abundant H2O2 into 1O2 and fTAT-Dox that can readily penetrate the cell membrane into the nucleus, chemical modification of nuclear DNAs was realized through the covalent cyclization reaction between furan and nucleobases of nuclear DNAs under the ignition of self-generative 1O2, which leads to significant DNA damage and enhanced therapeutic susceptibility. More notably, the sustained release of Dox within the nucleus greatly inhibits DNA transcription and translation leading to severe cancer cell apoptosis. In vivo studies in a multidrug-resistant MCF-7/ADR tumor model showed that the antitumor efficacy of FA(CT-fT-Dox) was 1.6-fold higher than FA(CT-T-Dox) without DNA modification functionality with a tumor suppression efficiency of 83.3%. This SiCMoND-assisting chemotherapy strategy provides a promising antitumor therapeutic modality and opens new avenues for battling multidrug-resistant tumors.

Mastitis is frequently triggered by the bacterial disruption of the epithelial cell barrier. The actin-related protein 2/3 complex (Arp2/3), a major endogenous protein involved in cytoskeletal regulation, plays a crucial role in preserving epithelial barrier integrity during inflammation; however, its specific role in mastitis progression remains unclear. This study aims to use lipopolysaccharide (LPS) to establish mammary alveolar cells-large T antigen cells (MAC-T is a bovine mammary epithelial cell line) and mouse models of mastitis, investigating the functional relationship between actin-related protein 2/3 complex subunits 3 (ARPC3) and 4 (ARPC4) and heat shock protein 70 (HSP70) during mammary epithelial cell inflammation and assessing its effects on apoptosis. Transcriptomic sequencing initially identified 48 differentially expressed genes associated with the bacterial invasion of epithelial cells and apoptosis. Further molecular biology analyses showed a significant upregulation of ARPC3/ARPC4 and HSP70 expression during inflammation, along with a marked increase in apoptosis rates. When ARPC3/ARPC4 was inhibited using CK666, HSP70 expression further increased compared to the LPS group, while inflammatory factors, apoptosis rates, and apoptosis-related protein expression were notably reduced. These findings indicate that targeting ARPC3/ARPC4 to regulate HSP70 can promote inflammation and apoptosis, highlighting its potential as a therapeutic target for mastitis.

Liver cancer is the third leading cause of death globally, with hepatitis B virus (HBV) infection being identified as the primary risk factor for its development. The occurrence of HBV-related hepatocellular carcinoma (HCC) is attributed to various mechanisms, such as chronic inflammation and liver cell regeneration induced by the cytotoxic immune response triggered by the virus, abnormal activation of oncogenes arising from HBV DNA insertion mutations, and epigenetic alterations mediated by viral oncoproteins. The envelope protein of the HBV virus, known as hepatitis B surface antigen (HBsAg), is a key indicator of increased risk for developing HCC in HBsAg-positive individuals. The HBsAg seroclearance status is found to be associated with recurrence in HCC patients undergoing hepatectomy. Additional evidence indicates that HBsAg is essential to the entire process of tumor development, from initiation to advancement, and acts as an oncoprotein involved in accelerating tumor progression. This review comprehensively analyzes the extensive effects and internal mechanisms of HBsAg during the various stages of the initiation and progression of HCC. Furthermore, it highlights the importance and potential applications of HBsAg in the realms of HCC early diagnosis and personalized therapeutic interventions. An in-depth understanding of the molecular mechanism of HBsAg in the occurrence and development of HCC is provided, which is expected to develop more precise and efficient strategies for the prevention and management of HCC in the future.

OBJECTIVES:This study aimed to investigate the differentially expressed microRNAs in erosive oral lichen planus, followed by analyzing how the overexpression of identified miR-516a-5p influences human oral mucosal fibroblasts. MATERIAL AND METHODS:High-throughput sequencing using tissues from patients and healthy individuals identified varying microRNA expression profiles in erosive oral lichen planus tissues. Bioinformatics analysis subsequently revealed the enriched pathways and targeted genes involved. In vitro experiments were performed to confirm the validity of bioinformatic findings. RESULTS:A total of 82 microRNAs were differentially expressed in erosive oral lichen planus tissues. These microRNAs are mainly linked to T helper cell differentiation that enriched in MAPK signaling pathways, as well as targeting mRNAs like MAPK11. Overexpression of miR-516a-5p resulted in a statistically significant decrease in MAPK11 mRNA level in human oral mucosal fibroblasts. Overexpression of miR-516a-5p increased TNF-α and IFN-γ levels, whereas it decreased IL-4, IL-6, IL-10, and IL-13 levels. Overexpression of miR-516a-5p enhanced both the proliferation and migration of human oral mucosal fibroblasts. CONCLUSIONS:The miR-516a-5p overexpression in patients with erosive oral lichen planus may contribute to the imbalance of T helper 1/2 cell-associated inflammatory cytokine expression in human oral mucosal fibroblasts by targeting MAPK11 mRNA, promoting their proliferative and migratory capacities.

BACKGROUND:Androgenetic alopecia (AGA) is the most common form of hair loss globally. Despite its prevalence, only two FDA-approved drugs-minoxidil and finasteride-are currently available, underscoring the urgent need to discover novel biomarkers and therapeutic targets for AGA diagnosis, treatment, and monitoring. OBJECTIVES:This study aimed to explore novel therapeutic targets and biomarkers for AGA and investigate the causal role of plasma metabolites mediating therapeutic targets in AGA. METHODS:Cis-expression quantitative trait loci (cis-eQTL) data were derived from the eQTLGen Consortium (31,684 samples). Genetic associations with AGA were obtained from the FinnGen cohort (220 cases, 219,249 controls), and the UK Biobank (66,172 cases and 140,864 controls). Colocalization and summary-data-based MR (SMR) analyses were performed to rank these candidate therapeutic targets. Additionally, Transcriptome-Wide Association Study (TWAS) and Multi-marker Analysis of GenoMic Annotation (MAGMA) analyses were conducted to prioritize potential biomarkers, while Phenome-wide association study (PheWAS), and drug prediction were used to identify therapeutic targets. Lastly, mediation analysis was applied to explore the role of metabolites in AGA treatment. RESULTS:Ten genes emerged as promising targets after multi-layer validation. Among them, SOD1 and KL were classified as tier 1 targets with strong evidence. NT5E, SQLE, and ADM were designated tier 2 with moderate support, while PAM, LAMC1, LAMC3, PRLR, and BRAF were tier 3 candidates. Polymerase Chain Reaction (qPCR) validation supported these findings. CONCLUSIONS:Our integrative multi-omics analysis identified 10 potential therapeutic targets and biomarkers for AGA. SOD1 and KL stand out as strong candidates, offering promising directions for future AGA therapies.

Sepsis is a major cause of mortality in neonates, yet understanding of sepsis-associated immune dysregulation in early life remains limited. Sepsis-induced thymus atrophy results in disruption of T cell development, accompanied by the dysfunction of thymic epithelial cells (TECs). Here, we sought to identify molecular mechanisms underlying TECs dysfunction while induced sepsis in neonatal mice and immortalized TECs cell line (iTECs) via lipopolysaccharide (LPS) treatment. We identified that LPS induced a reduction in thymocytes number starting at the double-negative stage of thymocyte development and significantly reduced numbers of naïve T cells and recent thymic emigrants (RTEs). Further we confirmed the alterations of intrathymic cytokines influencing T cell development and functionality through the FOXN1 signaling pathway upon exposure to LPS ex vivo and in vivo. LPS treatment decreased the number of cortical TECs (cTECs) and medullary TECs (mTECs) by enhancing the apoptosis of cTECs and decreasing the proliferation of mTECs. These findings provide valuable insights for further study on the innate and specific immunity in response to neonatal sepsis.

Previous studies have illustrated the pivotal role of coagulation biomarkers in the link between air pollution and cardiovascular disease (CVD). However, inconsistencies remain in the conclusions, with limited studies conducted in rural areas of China. We conducted a panel study in rural areas of Henan Province, China. Considering the potential effect modifications of atherosclerotic cardiovascular disease (ASCVD) risks, 104 participants were enrolled, comprising two matched groups: 52 with high ASCVD risks and 52 with low ASCVD risks. DNA methylation at CpG sites and coagulation indices were measured for all participants. Linear mixed-effect regression models were used to evaluate the associations between ambient air pollution, coagulation biomarkers, and DNA methylation. We observed that for every 5-day standard deviation (SD) increment of PM2.5 (11.91 μg/m³) and PM10 (13.65 μg/m³), fibrinogen increased by 7.70 % (95 %CI: 2.27, 13.12) and 8.50 % (95 %CI: 2.46, 14.55), respectively. SO2 (6.95 μg/m³) was associated with 40.25 % (95 %CI: 14.83, 65.67) increase in plasminogen activator inhibitor-1 (PAI-1). Decreased methylation at CpG sites was associated with exposure to air pollution. However, DNA methylation did not mediate the association between ambient air pollution and coagulation. Our study revealed the harmful impact of ambient air pollution on coagulation function but found no significant mediation effects of DNA methylation.

BackgroundAcute promyelocytic leukemia (APL) is rarely caused by the PLZF::RARα fusion gene. While APL patients with PLZF::RARα fusion commonly exhibit diverse hematologic symptoms, the presentation of myeloid sarcoma (MS) as an initial manifestation is infrequent.Case presentationA 61-year-old patient was referred to our hospital with 6-month history of low back pain and difficulty walking. Before this admission, spine magnetic resonance imaging (MRI) conducted at another hospital revealed multiple abnormal signals in the left iliac bone and vertebral bodies spanning the thoracic (T11-T12), lumbar (L1-L4), and sacral (S1/S3) regions. This led to a provisional diagnosis of bone tumors with an unknown cause. On admission, complete blood count (CBC) test and peripheral blood smear revealed a slightly increased counts of monocytes. Immunohistochemical staining of both spinal and bone marrow (BM) biopsy revealed positive expression for CD117, myeloperoxidase (MPO), and lysozyme. BM aspirate showed a significant elevation in the percentage of promyelocytes (21%), which were morphologically characterized by round nuclei and hypergranular cytoplasm. Multiparameter flow cytometry of BM aspirate revealed that blasts were positive for CD13, CD33, CD117, and MPO. Through the integrated application of chromosome analysis, fluorescence in situ hybridization (FISH), reverse transcriptase polymerase chain reaction (RT-PCR), and Sanger sequencing, it was determined that the patient possessed a normal karyotype and a rare cryptic PLZF::RARα fusion gene, confirming the diagnosis of APL.ConclusionIn the present study, we report the clinical features and outcome of a rare APL patient characterized by a cryptic PLZF::RARα fusion and spinal myeloid sarcoma (MS) as the initial presenting symptom. Our study not only offers valuable insights into the heterogeneity of APL clinical manifestations but also emphasizes the crucial need to promptly consider the potential link between APL and MS for ensuring a timely diagnosis and personalized treatments.

The anti-tumor efficacy of naturally derived photosensitizer-hypericin (Hy) is dampened by hypoxia and over-expressed glutathione in the tumor microenvironment (TME). For rewiring the TME, we encapsulated Hy to an intrinsic modifier-manganese oxide-formed nanorambutan (MnOx-Hy NR). In triple-negative breast cancer cells, MnOx-Hy NR not only consumed glutathione through Mn2+ and hypericin release but also facilitated O2 production to relieve hypoxia, through which the reactive oxygen species (ROS) generation was strengthened by endoplasmic reticulum targeting hypericin. In the meantime, glutathione consumption-induced glutathione peroxidase 4 (GPX4) inactivation and the elevation of lipid hydroperoxide (LPO) level further triggered ferroptosis. Then, the combination of PDT and ferroptosis contributed to a synergic immunogenic cell death (ICD) effect in 4 T1 cells, facilitating the adaptive anti-tumor immune response activation. Thereby, MnOx-Hy NR exhibited excellent anti-tumor effects both in primary and distant tumors through the abscopal effect, as well as significant lung metastasis inhibition in the 4 T1 mouse metastatic tumor model.

To advance the understanding and potential treatment strategies for triple‐negative breast cancer (TNBC), particularly focusing on its high metastatic propensity and uncertain molecular targets, a biomimetic tumor cell membrane‐encapsulated nanodelivery system is developed for enhanced immunotherapy. This system is assembled with the second near‐infrared (NIR‐II) photothermal agent, chemotherapeutic drug, and programmed death‐ligand 1 (PD‐L1) inhibitors camouflaged by TNBC cell membranes. An NIR‐II Ag2S quantum dots (QDs) is introduced for not only realizing pronounced imaging‐guided photothermal therapy (PTT), but also co‐activating immunogenic cell death (ICD) with chemotherapy. Homologous targeting and camouflage properties endowed the nanodelivery system with excellent biocompatibility and efficient delivery ability to the tumor site, demonstrating excellent synergistic therapeutic efficacy. The release of damage‐associated molecular patterns (DAMP) marked the induction of ICD, crucial for reshaping the immune microenvironment. Further integration of α‐PD‐L1 achieved a 56.5% immune checkpoint inhibition rate, synergistically amplifying immune response to ultimately activate key cytokines, thereby achieving pronounced anti‐tumor immunotherapy effects. Notably, this approach realized a considerable reduction of metastatic nodules by 51.2% in the TNBC lung metastasis model. The proposed nanodelivery system extended tumor remission and effectively reduced lung metastasis, paving the way for a reliable and promising approach in TNBC immunotherapy.

CRISPR technology has been used to revolutionize various facets of life sciences because of its potent gene editing capabilities. In particular, CRISPR technology is anticipated to be used to cure congenital disorders, and malignant cancers brought on by gene mutation. In this article, we introduce a Split-Cas9 system, in which Cas9 protein is split into two or more parts and recombined in cells to function specific induction circumstances. Split-Cas9 system can improve the therapeutic index of CRISPR technology by splitting Cas9 proteins into small fragments, thus enhancing their compatibility with virus vectors and precise temporal and spatial control. This article examined the combination mode of Split-Cas9 system, contrasted the differences in its split sites and activity efficiency, and discussed the use and clinical transformation in vivo and in vitro.

IntroductionMalonyl coenzyme A decarboxylase deficiency is caused by an abnormality in the MLYCD gene. The clinical manifestations of the disease involve multisystem and multiorgan.MethodsWe collected and analyzed a patient's clinical characteristics, genetic chain of evidence and RNA-seq. We use the search term “Malonyl-CoA Decarboxylase Deficiency” on Pubmed to collect cases reported.ResultsWe report a 3-year-old girl who is presented with developmental retardation, myocardial damage and elevated C3DC. High-throughput sequencing identified heterozygous mutation (c.798G>A, p.Q266?) in the patient inherited from her father. The other heterozygous mutation (c.641+5G>C) was found in the patient inherited from her mother. RNA-seq showed that there were 254 differential genes in this child, among which 153 genes were up-regulated and 101 genes were down-regulated. Exon jumping events occurred in exons encoding PRMT2 on the positive chain of chromosome 21, which led to abnormal splicing of PRMT2. (P<0.05, FDR<0.05). The result of SNP showed that there were multiple mutation sites on chromosome 1, which may affect the downstream gene variation at the DNA level. The literature review identified 54 cases described since 1984.DiscussionIt is the first report about the locus, adding a new item to the MLYCD mutation library. Developmental retardation and cardiomyopathy are the most common clinical manifestations, with commonly elevated malonate and malonyl carnitine levels in children.

OBJECTIVE:To study the cerebrospinal fluid (CSF) status and prognosis value in patients with newly diagnosed acute lymphoblastic leukemia (ALL) by flow cytometry (FCM).METHODS:The clinical features of the 75 newly diagnosed ALL patients from September 2020 to December 2021 in our centre were retrospective analyzed, as well as the bone marrow (BM) and CSF minimal residual disease (MRD) data, and the CSF conventional cytology data. Central nervous system infiltration(CNSI) positive was as CSF MRD positive by FCM or leukemia cells detected by conventional cytology. The status of CSF were compared and analyzed by FCM and conventional cytology, the clinical features and the prognosis value of different CNSI status in these patients were analyzed.RESULTS:Among 75 newly diagnosed ALL, 16 cases (21%) with CNSI positive (CNSI+) were detected by FCM, while only 2 positive cases (3%) were detected by conventional cytology. The CNSI+ rate detected by FCM was significantly higher than conventional cytology(P<0.05). Compared with CNSI- ALL patients, the median age of CNSI+ ALL patients was significantly younger, and the median platelet count was significantly lower, the difference was statistically significant (P<0.05). Up to follow-up time (August 31, 2022), four ALL patients were died, including 3 patients were CNSI- and 1 patient was CNSI+. Furthermore, three cases were primary disease relapse, including 1 case was CNSI+. There was no significant difference in overall survival (OS) rate and relapse-free survival (RFS) rate of the patients with different CNSI status.CONCLUSION:Compared with conventional cytology, FCM is a more sensitive assay to evaluate the central nervous system status in ALL patients. After active treatment, there was no significant difference in OS and RFS between patients with different CNSI status at diagnosis.

Pulmonary fibrosis is a complication in patients with coronavirus disease 2019 (COVID-19). Extensive pulmonary fibrosis is a severe threat to patients’ life and lung transplantation is last resort to prolong the life of patients. We reported a case of critical type COVID-19 patient, though various treatment measures were used, including anti-virus, anti-infection, improving immunity, convalescent plasma, prone position ventilation, and airway cleaning by fiber-optic bronchoscope, although his COVID-19 nucleic acid test turned negative, the patient still developed irreversible extensive pulmonary fibrosis, and respiratory mechanics suggested that lung compliance could not be effectively recovered. After being assisted by ventilator and extracorporeal membrane oxygenation for 73 days, he finally underwent double-lung transplantation. On the 2nd day after the operation, the alveolar lavage fluid of transplanted lung was examined by cytomorphology, and the morphology of alveolar epithelial cells was intact and normal. On the 20th day post-transplantation, the chest radiograph showed a large dense shadow in the middle of the right lung. On the 21st day, the patient underwent fiber-optic bronchoscopy, yeast-like fungal spores were found by cytomorphological examination from a brush smear of the right bronchus, which was confirmed as Candida parapsilosis infection by fungal culture. He recovered well due to the careful treatment and nursing in our hospital. Until July 29, 96 days after transplantation, the patient was recovery and discharged from hospital.

With the development of nanomedicine technology, stimuli-responsive nanocarriers play an increasingly important role in antitumor therapy. Compared with the normal physiological environment, the tumor microenvironment (TME) possesses several unique properties, including acidity, high glutathione (GSH) concentration, hypoxia, over-expressed enzymes and excessive reactive oxygen species (ROS), which are closely related to the occurrence and development of tumors. However, on the other hand, these properties could also be harnessed for smart drug delivery systems to release drugs specifically in tumor tissues. Stimuli-responsive nanoparticles (srNPs) can maintain stability at physiological conditions, while they could be triggered rapidly to release drugs by specific stimuli to prolong blood circulation and enhance cancer cellular uptake, thus achieving excellent therapeutic performance and improved biosafety. This review focuses on the design of srNPs based on several stimuli in the TME for the delivery of antitumor drugs. In addition, the challenges and prospects for the development of srNPs are discussed, which can possibly inspire researchers to develop srNPs for clinical applications in the future.

BACKGROUND:St John's Wort (Hypericum perforatum, SJW) is widely used to treat postpartum depression (PPD) because of its high safety. Hypericin (HY) is the main effective component of SJW. The physiological roles of NLRP3 inflammasome activation and glucocorticoid metabolism are closely linked to depression. But, it remains elusive whether HY relieve PPD through targeting NLRP3 inflammasome activation or other mechanism. This study aimed to clarify the therapeutic effects of HY on PPD model rats and its underlying mechanisms in vivo. METHODS:hormone-simulated pregnancy model was used, and behavioral tests was used to assess depressive state. Inflammatory factors in serum were tested by Enzyme-linked immunosorbent assay. RESULTS:Changes in the classic behavioral tests reflected that HY could alleviate the symptoms of PPD as effective as fluoxetine (FLU). Both of HY and FLU could significantly inhibit the protein expression of NLRP3, caspase-1 in hypothalamus and decrease the levels of inflammatory factors (IL-6, IL-1β, TNF - α) in serum. For hormone level determination, HY can not only significantly reduce the level of CORT, but also reverse the activity of 11β - HSD2 enzyme, which is different from FLU. LIMITATIONS:More experiments will be needed to verify the target of HY. CONCLUSION:All those data suggest that HY can effectively relieve PPD by reversing glucocorticoid metabolism, increasing ER expression, and then relieve neuroinflammation.