Abstract:The development and progression of heart failure involves vascular endothelial dysfunction，inflammation，and oxidative stress，and this pathophysiological process affects the activity of the nitric oxide（NO）-soluble guanylate cyclase（sGC）-cyclic guanosine monophosphate（cGMP） signaling pathway. Vericiguat can increase the level of cGMP by stimulating sGC，and as a second messenger to activate protein kinases，phosphodiesterases，and subsequent signaling pathways，cGMP can dilate blood vessels，improve coronary blood flow，and inhibit the progression of inflammation and myocardial fibrosis，thereby improving the prognosis of patients with heart failure. At present，several clinical studies have been conducted for vericiguat in the treatment of heart failure with reduced ejection fraction and heart failure with preserved ejection fraction，and its safety in the treatment of heart failure patients has been widely confirmed，but its efficacy varies in different types of heart failure patients. This article reviews the changes in the NO-sGC-cGMP pathway during the onset of heart failure，the mechanism of action of vericiguat，and the advances in vericiguat in the treatment of heart failure.

Abstract:The development and progression of nervous system diseases are often accompanied by abnormal neuronal programmed cell death. Acupuncture，as a common means of preventing and treating nervous system diseases，is worthy of in-depth discussion regarding its role in regulating imbalanced neuronal programmed cell death. Acupuncture can treat cerebral ischemia，cerebral hemorrhage，craniocerebral trauma，spinal cord injury，and Alzheimer’s disease mainly by regulating neuronal apoptosis，pyroptosis，autophagy，and ferroptosis. Therefore，this article reviews the role of acupuncture in regulating neuronal programmed cell death，aiming to explore the common biological mechanism of acupuncture in the treatment of various nervous system diseases and provide new ideas for relevant research.

Abstract:Sepsis and septic shock are common in intensive care units，with more than 18 million cases of severe sepsis worldwide each year. According to the epidemiological survey abroad，the case fatality rate of sepsis has exceeded that of myocardial infarction， so sepsis has become the main cause of death of non-cardiac patients in intensive care units. Medical advances have led to more and more innovative treatments for sepsis. Continuous blood purification is gradually emerging as a crucial early treatment modality for septic patients，while extracorporeal blood adsorption is also gaining attention for its therapeutic value in septic patients. This article aims to summarize the research progress of plasma inflammatory cytokine adsorption in the treatment of sepsis in recent years， as well as the common extracorporeal blood adsorption techniques that have been reported in existing research or applied clinically along with their research advances，thus providing a reference for better understanding its application value in clinical treatment and improving the prognosis，and offering help for the treatment of patients with sepsis and septic shock.

Abstract:Objective To establish a practical large animal model of intervertebral disc degeneration（IVDD） for the simulation of the influence of local factors in the human body and the role of pathophysiological stress load on IVDD.Methods In this study，lumbar dynamic and static instability（LDSI） surgery was performed to damage the posterior column structure of the goat spine； the muscles including erector spinae，latissimus dorsi，longissimus lumborum，and spinalis were ligated to destroy the dynamic stability of the lumbar spine，and the spinous process，supraspinous ligament，and interspinous ligament were ligated to destroy the static stability of the lumbar spine，resulting in the imbalance of dynamic and static forces of the lumbar spine and the loss of the stability of the posterior column. With biomechanical stability as the breakthrough point，a goat model of lumbar dynamic and static instability was established without destroying the structural integrity of the intervertebral disc，and during 52 weeks of postoperative follow-up，lumbar spine X-ray，magnetic resonance imaging（MRI），and histopathological changes were used to evaluate disc height index（DHI），Pfirrmann MRI grade，and Masuda histological score.Results In the LDSI group，the DHI of goat lumbar spine was 0.184±0.015 at week 0 before surgery，0.105±0.006 at 26 weeks after surgery，and 0.075±0.007 at 52 weeks after surgery （0 week vs. 26 weeks：P<0.05；26 weeks vs. 52 weeks：P<0.05）. In the LDSI group，the Pfirrmann grade of goat lumbar spine was 1.167±0.408 at week 0 before surgery，2.333±0.516 at 26 weeks after surgery，and 3.667±0.817 at 52 weeks after surgery（0 week vs. 26 weeks：P<0.05；26 weeks vs. 52 weeks：P<0.05）. In the LDSI group，the Masuda histological score of goat lumbar spine was 3.500±0.577 at week 0 before surgery，6.250±0.957 at 26 weeks after surgery，and 8.000±0.816 at 52 weeks after surgery（0 week vs. 26 weeks：P<0.05；26 weeks vs. 52 weeks：P<0.05）.Conclusion LDSI can cause the reduction in the height of the intervertebral disc，the blurring of endplate boundary，and the reduction in water content in goats. It simulates the process of IVDD caused by long-term repeated strain of human body without destroying the structural integrity of the intervertebral disc，which is more in line with the real condition of human body and may provide help for research on the pathogenesis of IVDD.

Abstract:Objective NLRP6（NOD-like receptor thermal protein domain associated protein 6），a recently identified member of the nucleotide-binding oligomerization domain（NOD）-like receptors family，is abundantly expressed in the intestine，liver，kidney，spleen，muscle，and other tissues or organs，playing a regulatory role in various biological processes such as inflammation，pyroptosis，and autophagy. Recently，NLRP6 was reported to exert a significant impact on the disease phenotypes of various tissues and organs under stress conditions. However，the role of NLRP6 in the growth and development of tissues and organs in a natural state remains unclear.Methods A mouse model of NLRP6 gene knockout was established using CRISPR/Cas9 gene editing technique. The mice were raised and observed for their growth and reproduction. The spleen，liver，heart，kidney，brain，limbs，and dorsal skin of the mice were dissected，sectioned，and stained to evaluate the effect of NLRP6 gene knockout on the macroscopic development of parenchymal organs and microscopic tissue structure.Results In the natural state，NLRP6 knockout shortened the sexual maturity in male mice，resulting in irreversible ulceration and atrophy of the testicles in adult male mice. NLRP6 gene knockout led to the rupture of striated muscle in the hindlimbs in adult male mice，resulting in obvious atrophy of the hindlimbs. NLRP6 gene knockout not only significantly increased the volume of the spleen（P<0.01）but also induced inflammatory cell infiltration in male mice. NLRP6 gene knockout caused significant ulcerous damage，collagen fiber proliferation，and inflammatory cell infiltration in the dorsal skin in male mice.Conclusion In the natural condition of growth and development，NLRP6 gene knockout selectively affects genital development and sexual maturity，hindlimb muscle development，the size and immune response of the spleen，and the structural integrity of the dorsal skin in mice. This effect is significantly androgen-dependent.

Abstract:Objective To investigate the effect and possible mechanisms of progranulin（PGRN） on acute lung injury（ALI） in sepsis.Methods C57BL/6 mice were randomly divided into normal control group（Control group），acute lung injury group（CLP group），and PGRN treatment group（CLP+PGRN group）. Cecal ligation and puncture（CLP） was used to establish a mouse model of septic ALI，and the mice in the CLP+PGRN group were given intraperitoneal injection of PGRN at half an hour after CLP treatment. The mice were anesthetized and sacrificed after 24 hours，and lung tissue was collected for HE staining to observe the pathological damage of lungs； the TUNEL method was used to observe cell apoptosis in lungs；immunofluorescent staining was used to measure the level of nuclear factor-kappa B（NF-κB） in lung tissue；Western blot was used to measure the expression levels of NF-κB，total p65，and phosphorylated p65（p-p65），and RT-qPCR was used to measure the levels of NF-κB and inflammatory factors.Results Compared with the Control group，the CLP group and the CLP+PGRN group had aggravated lung injury and significant increases in proinflammatory cytokines，cell apoptosis in lung tissue，and the expression levels of NF-κB，p65，and p-p65. Compared with the CLP group，the CLP+PGRN group had alleviation of lung injury and apoptosis，a reduction in proinflammatory cytokines，increases in anti-inflammatory cytokines，and significant reductions in the expression levels of NF-κB，p65，and p-p65.Conclusion PGRN can alleviate ALI in mice with sepsis，possibly by inhibiting the expression of NF-κB and p65 and the phosphorylation of p65.

Abstract:Objective To select genes associated with disulfidptosis-related myocardial ischemia-reperfusion injury（MIRI），and to explore their possible pathways of action.Methods We selected differentially expressed genes associated with MIRI between the 24 h group and the control group with the use of the limma R package； performed functional enrichment analysis on the genes through the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases with the use of the clusterProfiler R package；conducted enrichment analysis based on disulfidptosis-related gene set and GSE160516 expression data using the ssgsea method of the GSVA R package，and identified the expression of disulfidptosis-related genes in myocardial ischemia-reperfusion using a Venn diagram；calculated the correlations between disulfidptosis-related genes and genes associated with apoptosis factors，mitochondria，ferroptosis，and inflammation using the corr. test of the psych R package，and generated a heatmap； and clustered the expression patterns of MIRI transcriptome data at different time points using the Mfuzz R package，and identified time series-related differentially expressed disulfidptosis-related genes using a Venn diagram.Results A total of 17 differentially expressed disulfidptosis-related genes were determined in this study. Through correlation analysis of disulfidptosis-related genes and genes associated with inflammation，apoptosis，ferroptosis，and mitochondria as well as analysis of time series-related differentially expressed genes associated with disulfidptosis during myocardial ischemia-reperfusion，we finally identified the specific expression of disulfidptosis-related Flna，Myl6，and Tln1 genes at different time points pf MIRI.Conclusion The Flna，Myl6，and Tln1 gens may play crucial roles in MIRI，and these disulfidptosis-related genes are closely associated with mitochondria-related genes，which can be screening indicators for risk factors in patients with MIRI.

Abstract:Objective To observe the changes in scaffolding protein Homer protein homolog 1b and 1c（Homer1b/c），inositol 1，4，5-trisphosphate receptor（IP3R），metabotropic glutamate receptor 5（mGluR5），sh3 and multiple ankyrin repeat domains 3（Shank3） protein-related complexes，and common amino acids in the prefrontal cortex of CTNND2^-/- mice with autism，and to investigate the key targets that may be involved in the development of the disease in mice with autism.Methods Western blot（WB） was used to measure the changes in the protein expression levels of Homer1b/c，postsynaptic density-95（PSD-95），synaptophysin（SYP），and vesicular glutamate transporter 1（vGluT1） in the prefrontal cortex of CTNND2^-/- mice with autism；immunofluorescent（IF） staining was used to investigate the expression and colocalization of Homer1b/c with IP3R，mGluR5，or Shank3 proteins；co-immunoprecipitation（CO-IP） was used to observe the binding of Homer1b/c to IP3R，mGluR5 or Shank3；liquid chromatography（LC） was used to analyze the changes in common amino acids in the prefrontal cortex of mice.Results Compared with the control group，the CTNND2^-/- model mice had significant reductions in the expression of Homer1b/c（P=0.003），PSD-95（P=0.003），and SYP（P=0.046） in the prefrontal cortex and a significant reduction in the binding of Homer1b/c to IP3R，mGluR5，and Shank3 proteins，and there were no significant changes in the expression levels of the common excitatory neurotransmitter glutamate and the inhibitory neurotransmitter γ-aminobutyric acid in the prefrontal cortex（P=0.366 and 0.355），while there were significant increases in the expression levels of histidine（P=0.036） and tyrosine（P=0.030）.Conclusion There is low expression of Homer1b/c protein in the CTNND2^-/- mouse model of autism，and there is a reduction in the formation of Homer1b/c complexes with IP3R，Shank3，and mGluR5 proteins. It is speculated that low-expression Homer1b/c may be a key target for abnormal synaptic development in autism.

Abstract:Objective To explore the influence of optimized DNA extraction on genotyping of transgenic mice，and to compare it with commonly used reagent kits in the field of scientific research.Methods Based on our previous patent，we modified the DNA lysis buffer formula and experimental protocol. Genotyping and validation were carried out using musculin （a novel transcription factor）-transgenic mice and enhanced green fluorescent protein-transgenic mice.Results The DNA lysis solution was prepared immediately before use，and was composed of 100 μL 0.025 N NaOH，160 μL 0.5 M EDTA，and 40 mL ultrapure water. Each sample was mixed with 180 μL DNA lysis solution，at 100 ℃ for 30 min. Compared with the commonly used genotyping kits in relevant fields，the optimized DNA extraction method effectively shortened the genotyping time while ensuring the accuracy of identification，and moreover，the DNA lysis buffer preparation was simple and convenient，enabling more reaction times，and reducing reagent costs and workload considerably.Conclusion This study provides an economical，simple，and reliable DNA extraction technique for genotyping in transgenic mice，which deserves application and promotion.

Abstract:Objective To investigate the role and possible mechanisms of Maresin1（Mar1） in intestinal ischemia-reperfusion（IR） in mice.Methods Clamping of the superior mesenteric artery（SMA） was performed to establish a model of small intestinal IR. In the first part of the experiment，12 mice were randomly divided into Control group，IR group，and IR+Mar1 group，and in the second part，20 mice were randomly divided into Control group，IR group，IR+Mar1 group，IR+EX527 group，and IR+Mar1+EX527 group. Mar1 5 μg/kg was injected intraperitoneally at 30 min before surgery，and EX527 10 mg/kg was injected intraperitoneally at 1 day before surgery. In the control group，the SMA was isolated without clamping，and in the other model groups，the root of the SMA was clamped with a damage-free vascular clip，which was released after 45 min to establish a model of small intestinal IR. Venous blood and ileal specimens were collected at 4 hours after reperfusion in all groups. For the first part of the experiment，the levels of superoxide dismutase（SOD），malondialdehyde（MDA），and glutathione（GSH） in the intestinal tissue of each group were measured，as well as the serum level of FITC-Dextran 4000（FD-4）； immunofluorescent staining was used to measure the protein expression level of intestinal Occludin；HE staining was used to observe the pathological morphology of intestinal tissue. For the first and second parts of the experiment，western blot was used to measure the protein expression levels of Sirt1，P-NF-κB p65（P-p65），Caspase11，and GSDMD-N in intestinal tissue.Results In the first part of the experiment，compared with the Control group，the IR group had significant increases in the level of MDA in intestinal tissue，the content of FD-4 in serum，and the degree of pathological damage（P<0.01），significant reductions in the protein expression levels of SOD，GSH，and Sirt1，and significant increases in the protein expression levels of P-p65，Caspase11，and GSDMD-N； compared with the IR group，the IR+Mar1 group had significant reductions in the level of MDA in intestinal tissue，the content of FD-4 in serum，and the degree of pathological damage（P<0.05），significant increases in the protein expression levels of SOD，GSH，and Sirt1，and significant reductions in the protein expression levels of P-p65，Caspase11，and GSDMD-N. In the second part of the experiment，compared with the IR+Mar1 group，the IR+Mar1+EX527 group had a significant reduction in the protein expression level of Sirt1 and significant increases in the protein expression levels of P-p65，Caspase11，and GSDMD-N，while there was no significant difference in the expression of proteins between the IR+EX527 group and the IR+Mar1+EX527 group.Conclusion Mar1 pretreatment can alleviate small intestinal IR injury by inhibiting the Caspase11/GSDMD pathway via Sirt1.

Abstract:Objective To investigate the effect of the mitochondria-targeted antioxidant Mito-Tempo on acute liver injury in mice with sepsis and its possible mechanisms.Methods C57BL/6 mice were randomly divided into control group（Control group），cecal ligation puncture group（CLP group），and Mito-Tempo treatment group（CLP+Mito-Tempo group）. Cecal ligation and puncture（CLP） was used to establish a mouse model of sepsis and acute liver injury，and the mice in the CLP+Mito-Tempo group were pretreated with intraperitoneal injection of Mito-Tempo at 1 hour before CLP treatment. After 24 hours，the mice were anesthetized and sacrificed，and HE staining was used to observe liver histopathological injury；ELISA was used to measure the serum levels of inflammatory factors，and immunofluorescent staining was used to measure the level of reactive oxygen species（ROS） in liver tissue；an electron microscope was used to observe the morphology of mitochondria；Western blot was used to measure the expression levels of cleaved cysteinyl aspartate specific proteinase 1（cleaved caspase-1），cleaved gasdermin D（GSDMD），interleukin-1α（IL-1α），and interleukin-1β（IL-1β）.Results Compared with the Control group，the CLP group had aggravation of liver injury，an increase in ROS level，destroyed mitochondrial morphology，and increases in the expression levels of the pyroptosis-related proteins cleaved caspase-1，cleaved GSDMD，IL-1α，and IL-1β. Compared with the CLP group，the CLP+Mito-Tempo group had alleviation of liver injury，a reduction in ROS level，partial restoration of mitochondrial morphology，and significant reductions in the expression levels of the pyroptosis-related proteins cleaved caspase-1，cleaved GSDMD，IL-1α，and IL-1β.Conclusion Mito-Tempo can alleviate acute liver injury in mice with sepsis，possibly by reducing the level of oxidative stress and inhibiting pyroptosis.

Abstract:Objective To investigate the immune cells with significant infiltration and key immune-related genes in the progression of peri-implantitis based on bioinformatics analysis.Methods The GSE106090，GSE33774，and GSE57631 datasets from the NCBI Gene Expression Omnibus（GEO） were integrated. The single-sample gene set enrichment analysis（ssGSEA） was used to assess the immune cell infiltration score of peri-implantitis tissue and healthy gingival tissue，and the least absolute shrinkage and selection operator（LASSO） regression analysis was used to identify key immune genes.Results After the three datasets were integrated and the batch effect was removed，the ClusterProfiler package was used to perform gene ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） Gene Set Enrichment Analysis（GSEA） for peri-implantitis to identify significantly upregulated and downregulated signaling pathways and biological processes. The differentially expressed genes were intersected with the immune-related genes obtained from the ImmPort database，and key immune genes of the disease were successfully identified by the LASSO regression analysis，including C-C motif chemokine ligand 18（CCL18），interleukin-1β（IL1B），interleukin-6（IL6），complement C3（C3），natriuretic peptide receptor 3（NPR3），peptidase inhibitor 3（PI3），leukocyte immunoglobulin like receptor B3（LILRB3），and leucine rich repeat containing G protein-coupled receptor 4（LGR4）. Subsequently，a correlation analysis was conducted with ssGSEA immune infiltration score，and the results showed varying degrees of correlation between these genes and the 23 types of immune cells with a significant increase in peri-implant soft tissue. GO and KEGG enrichment analyses showed that the genes such as IL1B，IL6，CCL18，C3，LGR4，PI3，and LILRB3 were mainly involved in the biological processes such as humoral immunity，adaptive immunity，leukocyte migration，and skin epidermal development，while NPR3 was mainly associated with the biological processes such as leukocyte proliferation and body fluid regulation.Conclusion Differentially expressed immune-related genes are obtained by the bioinformatics method，and eight key immune genes are identified，which participate in multiple links of immune response and inflammatory response in peri-implantitis and exhibit high sensitivity to the disease background of peri-implantitis. The identification of these immune genes provides important molecular targets for a deeper understanding of the pathogenesis of peri-implantitis and the development of novel therapeutic strategies.

Abstract:Objective To investigate the metabolic disorders induced by intact-protein enteral nutrition formula in sepsis through metabolomics methods，and to provide new theoretical and experimental bases for the clinical treatment of sepsis.Methods Male mice，aged 8-12 weeks，were randomly divided into sham-operation group（Sham group），sepsis group（CLP），and sepsis+intact-protein enteral nutrition group（CLP+IPEN group），with 6 mice in each group. The mice in the CLP group were treated with cecal ligation and puncture to induce sepsis，while those in the Sham group were given laparotomy alone without ligation and puncture. The mice in the CLP+IPEN group received additional intact-protein enteral nutrition formula after surgery. Daily weight changes were monitored for 7 days，and samples were collected after 3 days of modeling and feeding. Staining was used to observe the histopathological changes of the ileum，and quantitative real-time PCR was used to measure the expression of different proteins. Differentially expressed metabolites in the treatment of sepsis with intact-protein enteral nutrition formula were identified based on specific criteria.Results There were 15 differentially expressed metabolites between the CLP group and the CLP+IPEN group. Compared with the CLP group，the CLP+IPEN group had significant increases in the content of five metabolites including dimethyl 3-hydroxy-3-methylpentane-1，5-dioate，malonic acid，and L-Serine，N-（methoxycarbonyl）-methyl ester（P<0.05）. Throughout the experiment，all three groups of mice showed a gradual reduction in body weight，and the CLP group showed the most significant weight loss on day 4（P<0.05），suggesting that intact-protein enteral nutrition formula could alleviate weight loss in mice with sepsis. The CLP+IPEN group had a significantly lower Chiu score than the CLP group（P<0.05），indicating a notable reduction in intestinal mucosal injury. Both the CLP group and the Sham group had significant increases in the expression of occludin，zonula occludens-1（ZO-1），and MUC2，suggesting that sepsis caused impairment of intestinal barrier function. Compared with the CLP group，the CLP+IPEN group had significant reductions in the expression of occludin，ZO-1，and MUC2（P<0.05）.Conclusion This study investigates the metabolic disorders induced by intact-protein enteral nutrition formula in sepsis through metabolomics methods，and the results show that intact-protein enteral nutrition formula can alleviate metabolic disorders in sepsis-related intestinal injury by regulating linoleic acid metabolism，biosynthesis of unsaturated fatty acids，biosynthesis of fatty acids，and metabolism of cytochrome P450 substances. In addition，such formulas have the potential in enhancing intestinal barrier function，mitigating weight loss in mice，and reducing the severity of intestinal injury，thereby laying a foundation for strengthening the efficacy of sepsis treatment.

Abstract:Objective To study the neuroprotective effect of Xiaoyaosan and its chemical composition，and to identify the active ingredients in Xiaoyaosan responsible for neuroprotection.Methods Xiaoyaosan was extracted using water，and the chemical composition of extract was analyzed using high-resolution mass spectrometry and liquid chromatography. Moreover，we prepared Xiaoyaosan-containing serum and established a corticosterone（CORT，400 μmol/L） -induced PC12 cell injury model to evaluate the impact of the drug-containing serum on the proliferation rate of PC12 cells. Then we used SIMCA software to analyze the correlations between cell proliferation rate and drug components to identify the compounds in Xiaoyaosan that may have neuroprotective effects.Results Compared with the model group，the drug-containing serum could reduce the cell injury induced by CORT and promote cell proliferation（P=0.000）. Analysis of liquid chromatography-mass spectrometry data in software showed that the main medicinal compounds were：paeoniflorin，glycyrrhizic acid，liquiritin，rosmarinic acid，gallic acid，2-phenylacetaldehyde，（15Z）-9，12，13-trihydroxy-15-octadecenoic acid，salvianolic acid B，and licorice saponin G2. The experimental results of individual compounds showed that phenylacetaldehyde was effective in neuroprotection（P=0.000）.Conclusion This research proves that Xiaoyaosan has neuroprotective effect. Fifty-five compounds were identified as potential ingredients involved in neuroprotection. Seven compounds，previously unreported and possessing potential neuroprotective properties，were identified in Xiaoyaosan. In addition，we demonstrate that phenylacetaldehyde has a neuroprotective effect，which has not been reported. The results of this study provide a reference for elucidating the material basis of the neuroprotective effect of Xiaoyaosan，and also provide data support for expanding the clinical application of Xiaoyaosan.

Abstract:Objective To investigate the effects of MK8719 （an inhibitor of O-linked N-acetylglucosamine［O-GlcNAc］ hydrolase） in a rat model of cerebral ischemic injury.Methods A rat middle cerebral artery occlusion model was established to simulate cerebral ischemia/reperfusion injury. We assessed cerebral infarct volume with 2，3，5-triphenyltetrazolium chloride staining；evaluated neuromotor function using the modified Neurological Severity Score；observed cerebral tissue changes after injury with Nissl staining and HE staining；and assessed the activation of anti-inflammatory microglia by immunofluorescence assay. An in-vitro BV2 microglia-based oxygen and glucose deprivation/re-oxygenation model was established to simulate ischemia-hypoxia/reperfusion injury. We measured the levels of total signal transducer and activator of transcription 6（STAT6），nuclear STAT6，phosphorylated STAT6，and O-GlcNAcylated STAT6 by Western blot；and measured the levels of pro-inflammatory interleukin（IL）-6 and IL-1β and anti-inflammatory IL-10 and transforming growth factor-β（TGF-β） released from microglia by enzyme-linked immunosorbent assay.Results The model rats treated with MK8719 showed a significantly smaller cerebral infarct size，significantly alleviated neurological deficits，and a significantly higher proportion of anti-inflammatory microglia. BV2 cells treated with MK8719 showed significantly increased expression of O-GlcNAcylated STAT6，phosphorylated STAT6（P<0.001），and nuclear STAT6，significantly reduced release of IL-6 and IL-1β（P<0.001），and significantly increased release of IL-10 and TGF-β（P<0.001）.Conclusion MK8719 can produce neuroprotective effects in rats with cerebral ischemic injury，which may be mediated by STAT6 activating anti-inflammatory microglia.

Abstract:Objective To elucidate the effect of Maresin-1（MaR1） on chronic social defeated stress（CSDS）-induced depression-like behaviors in adolescent mice（5-8 weeks old），validate its role in CSDS-induced neuroinflammation，and provide a reference for understanding the molecular mechanisms of depression and exploring biomarkers.Methods Multiple methods were used to measure depression-like behaviors and neuroinflammation in C57BL/6J mice ten days after CSDS induction. The mice were treated with MaR1（5 μg/kg） intravenously every two days to observe its effect on CSDS-induced depression-like behaviors and neuroinflammation. Behavioral experiments were followed by positron emission tomography-computerized tomography（PET-CT） scanning and quantitative analysis of PET images. The mouse brain tissue samples were collected for immunofluorescence staining，and the immunofluorescence intensities of Iba-1 cells in the hippocampal region and translocator protein（TSPO） were calculated using Image J. The mouse hippocampus was dissected on ice，immediately frozen in liquid nitrogen，and stored at -80°C for subsequent RNA extraction. A kit was used to measure the levels of tumor necrosis factor-α（TNF-α），interleukin-1 beta（IL-1β），and IL-4.Results Compared to the control group，mice subjected to CSDS stress showed a lower sucrose preference ratio（P=0.003），lower social interaction ratio（P=0.000），longer immobility time（P=0.002），and microglial cell activation in the hippocampal region evidenced by increased standardized uptake values（P=0.020），enhanced immunofluorescence intensity of Iba-1 and TSPO（P=0.000），and increased proinflammatory cytokines IL-1β and TNF-α（P=0.016，0.036）. In contrast，MaR1 improved CSDS-induced depression-like behaviors，inhibited microglia activation，and reduced the expression of proinflammatory factors.Conclusion MaR1 can alleviate CSDS-induced depression-like behaviors in adolescent mice and inhibit the activation of microglia. Neuroinflammation is a potential pathogenic factor for depression in adolescents，and drugs with anti-inflammatory properties such as MaR1 hold promise for use as a clinically relevant antidepressant，which needs further investigation.

Abstract:Objective To study and develop a three-dimensional visualization model that automatically reconstructs common brain tumors and important structures around them based on multimodal magnetic resonance imaging（MRI） data of the head and to validate its performance and clinical applicability.Methods Multimodal MRI data of the head with common brain tumors were collected and divided into training set，validation set，and clinical testing set. In the training and verification sets，the system's ability to automatically segment and reconstruct brain tumors and surrounding structures was trained through the algorithm of 3D depth convolutional neural network. In the clinical testing set，the reconstruction was completed by the system and a human，respectively，and the reconstruction efficiency and image quality were compared between the two methods.Results The time spent on completing the integrated model reconstruction of a tumor and its surrounding structure was significantly reduced from 5442±623 seconds （by a human） to （657±78） seconds（by the system）（t=27.530，P=0.000）. Meanwhile，the model reconstructed by the system had high consistency with the original image（Dice coefficient=0.92），and there was no significant difference in the image quality between the system and human reconstruction.Conclusion The automatic segmentation and fully automatic 3D visualization reconstruction of brain tumors and their surrounding structures using algorithms such as deep learning based on multimodal imaging data are accurate，efficient，and reliable，which is of great significance in the diagnosis of brain tumors and the formulation of surgical plans.

Abstract:Objective To investigate the influencing factors for early miscarriage in in patients with thin endometrium during fresh embryo transfer based on multiple machine learning methods，to establish a predictive model，and to provide reasonable ideas for preventing early miscarriage in patients with thin endometrium undergoing fresh embryo transfer.Methods A total of 1153 patients with thin endometrium who underwent fresh embryo transfer for the first time were enrolled in this study，and LASSO regression and random forest recursive feature elimination（RFE） were used for feature selection. Six machine learning models were developed and compared in terms of cross validation，accuracy，sensitivity，recall rate，f1 value，area under the ROC curve，and calibration curve. SHAP plots were used to elucidate the influencing factors for early miscarriage.Results A total of 29 feature variables were identified by LASSO regression and random forest RFE and were included in the six machine learning models，among which the multilayer perceptron model showed the best discriminatory ability for early miscarriage，with an area under the ROC curve of 0.803（95%CI=0.772-0.834）. The random forest，XGBoost，and AdaBoost models had an area under the ROC curve of >0.7.Conclusion This study establishes a machine learning-based predictive model for early miscarriage in patients with thin endometrium during fresh embryo transfer，and validation of various evaluation metrics shows that the model has good performance and can help clinicians to achieve the early diagnosis of patients，thereby providing ideas for improving the pregnancy outcome of patients at high risk of early miscarriage in the future.

Abstract:Objective To prospectively study the abundance and diversity of bacterial flora in the colostrum of postpartum women with gestational diabetes mellitus（GDM） and normal postpartum women.Methods According to the inclusion criteria，we enrolled 30 postpartum women with GDM and 30 healthy postpartum controls，all undergoing a cesarean delivery. Colostrum samples were collected from each subject to isolate DNA for high-throughput sequencing of the 16s rRNA V3-V4 amplicon using the Illumina MiSeq platform.Results The abundance-based coverage estimator for evaluating microbial richness was significantly different between the normal group and the GDM group（P=0.039）. The two groups showed no significant difference in alpha diversity，but differed significantly in beta diversity（P=0.001）. Compared with the control group，the GDM group showed lower mean relative abundance levels of the Firmicutes and Proteobacteria phyla，Streptococcaceae and Gemellaceae families，and Streptococcus and Roseburia genera； and higher mean relative abundance levels of the Actinobacteria phylum，Staphylococcaceae family，and Staphylococcus genus in the milk.Conclusion The abundance and diversity of colostrum microbiota are different between GDM mothers and healthy mothers，and the decreased relative abundance of Firmicutes and Proteobacteria in the breast milk of women with GDM may influence the establishment of gut microbiota and the growth and development of their children in the early stage. Quantifying the composition of breast milk microbiota has special significance for GDM mothers and their offspring.

Abstract:Objective To investigate the accuracy of a model established based on machine learning and computed tomography（CT） radiomics features in predicting vertebral fragility fractures in patients with type 2 diabetes mellitus（T2DM）.Methods A retrospective analysis was performed for the CT images and clinical data of 140 patients，among whom there were 70 T2DM patients with newly diagnosed vertebral fragility fractures and 70 patients in the control group. The previous CT images and clinical data of 18 patients（16 T2DM patients with vertebral fragility fractures and 2 patients in the control group） were collected as an external validation set. The optimal features were screened by the univariate analysis，the Pearson correlation analysis，minimum redundancy maximum relevance algorithm，the binary logistic regression analysis，and the least absolute shrinkage and selection operator regression model，and then a predictive model was constructed by support vector machine，multi-layer perceptron，and eXtreme gradient boosting（XGBoost） classifiers. The area under the ROC curve（AUC） was used to evaluate the predictive performance of the model.Results A total of 1 037 radiomics features were extracted from the CT images of each patient and were then simplified into 14 radiomics features. Among the 17 clinical features，sex，age，and body mass index were independent factors for predicting outcome. XGBoost classifier showed the best performance，and the XGBoost model showed an AUC of 1.000，0.929，and 1.000，respectively，in the training set and an AUC of 0.954，0.862，and 0.969，respectively，in the test set.Conclusion The XGBoost model based on clinical and radiomics features can be used as a noninvasive tool for predicting vertebral fragility fractures in T2DM patients.

Abstract:Objective To investigate the clinical value of CXC chemokine receptor type 4（CXCR4）-targeting ⁶⁸Ga-Pentixafor positron emission tomography/computed tomography（PET/CT） radionuclide-based imaging in the functional localization of the dominant side and prognosis of primary aldosteronism（PA）.Methods A total of 66 inpatients diagnosed with PA in The First Affiliated Hospital of Chongqing Medical University from March 2022 to May 2023 were selected. All patients were examined by PET/CT and adrenal vein sampling（AVS），and underwent unilateral or partial laparoscopic adrenalectomy. The coincidence rate of PET/CT and AVS in the diagnosis of PA lateralization was analyzed and compared. According to the improvement in blood pressure，medication，and blood potassium level during postoperative follow-up，the accuracy rate of functional localization diagnosis on the dominant side of PA by PET/CT and the predictive value of maximum standardized uptake value（SUVmax） of lesions for postoperative prognosis of patients were evaluated.Results Among the 66 surgical patients，unilateral adrenalectomy was performed in 63 patients and partial adrenalectomy in 3 patients. Postoperative pathological examinations showed adenoma in 58 patients and hyperplasia in 8 patients. The coincidence rate of PET/CT and AVS in the diagnosis of PA lateralization was 83.3%（55/66）. Based on the postoperative clinical benefit，the accuracy rates of PET/CT and AVS in the functional localization diagnosis of the dominant side of PA were 88.14%（52/59） and 93.22%（55/59），respectively. SUVmax in postoperative cured patients［14.70 （8.75，19.45）］ was significantly higher than that in postoperative improved patients［10.90 （6.65，14.10）］（P=0.026）. Preoperative SUVmax was positively correlated with postoperative aldosterone decrease，aldosterone/renin ratio decrease，and serum potassium increase（r=0.267，0.365，and 0.392，P=0.034，0.003，and 0.001，respectively）.Conclusion CXCR4-targeting ⁶⁸Ga-Pentixafor PET/CT for localization diagnosis of the dominant side of PA has an accuracy rate close to that of AVS，but with the advantages of repeatability and non-invasiveness. The higher the SUVmax，the more obvious the postoperative clinical benefit，showing a certain prognostic value.