Abstract:Objective：This study aims to investigate the role and mechanism of macrophage scavenger receptor 1（MSR1）in the process of white adipose thermogenesis induced by cold exposure. Methods：The expression of MSR1 and markers of the thermogenic capacity of adipose（UCP1，Cidea，Cox8b）in subcutaneous white adipose tissue（scWAT）and brown adipose tissue（BAT）of wild type mice（MSR1 ^+/+）and MSR1 knockout mice（MSR1^-/-）fed with common diet（CD）were detected by qRT - PCR，Western blot and immunohistochemistry after 1 or 14 days of cold exposure. The polarization of macrophages in scWAT of MSR1^+/+ and MSR1^-/- mice fed with CD after 30 days of cold exposure were detected by qRT-PCR and flow cytometry. Obese mouse model was established by high fat diet（HFD），the weight changes were monitored in MSR1^+/+ and MSR1^-/- mice fed with CD or HFD for 12 weeks，and the metabolic cage method was used to monitor the changes of O₂ consumption and heat production. The expression of thermogenic genes in scWAT and BAT of mice fed with HFD for 12 weeks were detected by qRT-PCR and immunohistochemistry after 7 days of cold exposure. In vitro， macrophage conditioned medium was used to stimulate the differentiation of mouse preadipocytes，and the expression of thermogenic genes of mature adipocytes were detected by qRT-PCR. Results：Compared with MSR1^+/+ mice，the expression of thermogenic genes in adipose tissue of MSR1^-/- mice was significantly decreased. Further，the number of M2 macrophages in scWAT of MSR1^-/- mice decreased significantly. After fed with HFD for 12 weeks，MSR1^-/- mice had significantly higher weight，lower O₂ consumption and heat production. The thermogenic capacity of adipose tissue in MSR1^-/- HFD mice was significantly reduced compared with MSR1 ^+/+ HFD mice after cold exposure. In vitro cell studies，compared with the mature adipocytes induced by peritoneal macrophage conditioned medium in MSR1 ^+/+ mice，the expression of thermogenic genes in mature adipocytes induced by peritoneal macrophage conditioned medium in MSR1^-/- mice was significantly reduced. Conclusion：After cold exposure，MSR1 increases the thermogenic capacity of adipose tissue by promoting the polarization of M2 macrophages.

Abstract:Objective：The current study aims to synthesize hypochloric acid（HClO）fluorescent probes targeting myeloperoxidase （MPO）and evaluate its HClO tracing activity. Methods：Si-rhodamine was used as the fluorophore to synthesize SiRho-GABA-KYC. The UV spectrum，fluorescence spectrum，and pH stability and selectivity were detected with UV spectrophotometer and fluorescence spectrophotometer. Cytotoxicity was detected with CCK - 8 method，and cell fluorescence imaging was performed by confocal microscopy. Results：SiRho -GABA -KYC was synthesized，with a high response to HClO，a good selectivity，and a low cytotoxicity， which can trace changes in HClO concentration in HeLa cells. Conclusion：The probe SiRho-GABA-KYC can be used to detect HClO concentration，which in turn reflects MPO catalytic activity.

Abstract:Objective：To investigate the mechanism by which Notch1 signaling regulates acetyl-para-aminophenol（APAP）-induced liver injury（AILI）via TAK1. Methods：AILI models were constructed on myeloid-specific Notch1 knockout（Notch1^M-KO）and floxed Notch1（Notch1^FL/FL）mice by intraperitoneal injection of APAP. Serum samples of mice were collected for detection of liver function and cytokines by fully automated biochemical analyser and enzyme-linked immunoassay（ELISA），respectively. The pathological damage of liver tissue was observed by HE staining，and the degree of liver tissue damage was evaluated by Suzuki score. Western blot analysis was performed to detect the expression levels of TAK1，phospho -TAK1，p65，phospho -p65，caspase -8，receptor -interacting protein kinase1（RIPK1），and phospho-mixed lineage kinase domain-like protein（MLKL）in the liver tissue. The expressions of CD11b，p-TAK1 and the level of reactive oxygen species（ROS）were observed by immunofluorescence staining. Results：After injected with APAP intraperitoneally in mice，liver histopathological examination suggested increased hepatocyte volume，sinus congestion，and extensive necrosis. Compared with Notch1^FL/FL group，Notch1^{M- KO} mice showed significantly elevated serum alanine aminotransferase（ALT） and aspartate aminotransferase（AST），increased inflammatory factor levels. HE staining showed more pronounced increase in hepatocyte volume，accompanied by extensive necrosis and increased infiltration of inflammatory cells. Additionally，the primary hepatocytes showed higher levels of ROS when assessed using the DCF probe. The expression of p-TAK1 in liver tissue elevated，and the expression of caspase-8 was down-regulated，while the expressions of RIPK1 and p-MLKL were up- regulated. Conclusion：In AILI，myeloid-specific Notch1 knockout activates TAK1 expression，which also decreases caspase-8 levels and promotes the RIPK1-MLKL necroptosis pathway，aggravating the liver injury.

Abstract:Objective：This study aims to explore the prognostic value of butyrylcholinesterase（BCHE）in gastric cancer（GC）and analyze its impact on the biological functions of gastric cancer cells. Methods：Firstly，Lasso regression method was used to screen prognostic genes，and the relationships between BCHE expression levels and clinical pathological parameters were verified using chi -square test. In addition，TIMER 2.0 database and CIBERSORT algorithm were utilized to investigate the correlation between BCHE and immune cell infiltration，and enrichment analysis was performed using WGCNA algorithm and DAVID Bioinformatics Resources database. Finally，the expression levels of BCHE in normal gastric epithelial cell line（GES-1）and gastric cancer cell lines （HGC27 and MKN1）were detected by real -time qPCR. Following transient transfection of small interfering RNA was conducted to knockdown the expression of BCHE in HGC27 and MKN1 cell lines. Cell proliferation was detected by CCK-8 and colony formation assay. Cell adhesion ability was detected by adhesion assay. Cell migration and invasion were detected by transwell and scratch assay. Results：Fifteen genes related to the prognosis of GC patients were screened out using Lasso regression analysis. Among them，BCHE has the best predictive value. Further analysis indicated that the expression level of BCHE in GC tissues was higher than those in the adjacent tissues or healthy controls，while the expression of BCHE in tumor cells was closely related to immune cell infiltration related molecules. Enrichment analysis showed that the high expression of BCHE was related to cell proliferation，migration and adhesion. The results of in vitro experiments further confirmed that reducing the expression of BCHE significantly inhibited the malignant biological function of gastric cancer cell line. Conclusion：BCHE serve as a prognostic biomarker for GC and can promote immune cell infiltration in tumors. In addition，reducing the expression of BCHE can inhibit its mediated malignant biological function.

Abstract:Objective：To construct lecithin - cholesterolacyl transferase（LCAT）knock -in mice by CRISPR/Cas9 - mediated gene editing and to obtain liver-specific overexpression of Lcat mice by mating with liver-specific Cre-expressing transgenic mice. Providing an animal model for the study of the mechanism of the Lcat gene in the development of liver-related metabolic diseases. Methods：Lcat knock -in mice were constructed by CRISPR/Cas9 technology；Liver - specific Cre- expressing transgenic mice were mated with Lcat knock -in mice to obtain liver -specific overexpressing Lcat mice；Genotyping mice by PCR；Quantitative real -time PCR（qPCR）and Western blot（WB）techniques were used to verify the expression of Lcat gene in C57BL/6 mice. Results：The PCR results showed that the liver-specific overexpression of Lcat gene in mice was successfully constructed；the qPCR results showed that the Lcat gene was specifically highly expressed in the liver，and the liver of knock -in mice showed higher Lcat expression；the WB results showed that LCAT protein was more highly expressed in the liver of liver-specific Lcat knock-in mice. Conclusion：Liver-specific overexpression of Lcat gene mice were successfully constructed，providing a platform for exploring the function of the Lcat gene at animal level in liver-related metabolic diseases and the associated pathogenesis.

Abstract:Objective：To study the effects of different bonding systems and aging treatment on the bonding strength between resin ceramic composites and dentin. Methods：A new hybrid ceramic restorative material（Lava^TM Ultimate excellent toughness porcelain） was used in the current study. In the first part of the experiment，the prepared isolated teeth were randomly divided into three groups：a two-step self-etching universal adhesive system，a total acid etching adhesive system，and a one-step self-etching universal adhesive system. The excellent toughness ceramic block was bonded to the isolated dentin surface. The static fracture strength of each group was measured using a microcomputer controlled electronic universal experimental machine，and the fracture morphology was observed. In the second part of the experiment，the shear specimens of the above-mentioned three adhesive systems were immersed in three different solutions（cola，soda water and artificial saliva）for 30 days to compare the difference of shear strength among the groups. Results：The shear strength values of the one-step and the two-step self-etching universal adhesive systems were both significantly higher than that of the total acid etching adhesive system，while the difference in bonding performance between the one-step universal bonding system and the two -step self etching universal bonding system was not statistically significant. The shear strength of the three bonding systems decreased after acid and alkali immersion aging，but without significar differences. And there was no statistical difference in the influence of three different solutions on shear strength. Conclusion：The shear strength between LavaTM Ultimate and teeth of the three adhesive systems meets clinical requirements，and acid and alkali aging treatment may not affect the shear strength of the three bonding systems.

Abstract:Objective：To explore the changes of serum interleukin（IL）- 9 level in patients with acute cerebral infarction and evaluate its value in prediction of early neurological deterioration（END）. Methods：A total of 106 patients with cerebral infarction were collected. According to whether or not END occurred，the patients were divided into END group（42 cases）and non -END group（64 cases）. The general data of patients were collected，and the National Institute of Health stroke scale（NIHSS）score was recorded，and serum biochemical indexes，serum IL-9，C-reactive protein（CRP）and IL-6 levels at baseline were detected. Pearson or Spearman correlation analysis was used to evaluate the correlation. Logistic regression was used to analyze the factors affecting the occurrence of END in patients with cerebral infarction，and ROC curve was drawn to evaluate the predictive value of serum IL-9 level in the occurrence of END after cerebral infarction. Results：The proportion of diabetes mellitus，carotid artery stenosis ＞50%，low density lipoprotein，glycosylated hemoglobin，cerebral infarction volume and NIHSS score at admission in END group were all higher than those in non-END group（P ＜ 0.05）. The level of serum IL-9 in the END group was significantly higher than that in the non-END group（P ＜ 0.01）. The level of serum IL-9 in patients with cerebral infarction was positively correlated with NIHSS score at admission （r=0.535，P ＜ 0.01）. Logistic regression showed that serum IL -9 level，carotid artery stenosis ＞50%，cerebral infarction volume and NIHSS score at admission were risk factors for END（P ＜ 0.01）. The area under ROC curve of serum IL - 9 level predicting END occurrence was 0.815. Serum IL-9 level was positively correlated with serum CRP level（r=0.648，P ＜ 0.01）and serum IL-6 level （r=0.765，P ＜ 0.01），respectively. Conclusion：Serum IL-9 level is significantly increased in patients with cerebral infarction END， which has a good predictive effect on the occurrence of END.

Abstract:Objective：To investigate the application value of Doppler uterine artery imaging and pelvic ultrasound combined with morning urine gonadotropin in the preliminary diagnosis of central precocious puberty（CPP）in girls. Methods：A total of 96 precocious girls admitted to the Department of Pediatrics，Huai’an Clinical College，Xuzhou Medical University from April 2022 to May 2023 were recruited as the study objects. General data were collected，serum basic luteinizing hormone（LH），follicle stimulating hormone（FSH），and estradiol levels were examined，morning urine LH and FSH were determined，and bone age was detected. At the same time，pelvic Doppler ultrasonography was performed to evaluate the uterine artery pulse index（PI），long diameter，transverse diameter and anteroposterior diameter of uterine，uterine volume，and ovarian volume. The girls were divided into the non-CPP group and the CPP group according to the results of GnRH stimulation test. Statistical software was used to analyze and integrate relevant data. Results：①The level of the uterine artery PI in the CPP group was significantly lower than that in the non -CPP group，while uterine long diameter as well as the level of morning urine LH in the CPP group were significantly higher than those in the non-CPP group（P ＜ 0.05）. ②Correlation analysis showed that uterine artery PI was negatively correlated with morning urine LH，morning urine FSH，long diameter，transverse diameter，anteroposterior diameter of uterine，uterine volume，ovarian volume，and serum LH peak value （P ＜ 0.05），but had no significant correlation with serum FSH peak value（P ＞ 0.05）. Uterine long diameter was positively correlated with morning urine LH，morning urine FSH，uterine transverse diameter，anteroposterior diameter，uterine volume，ovarian volume，and serum LH peak value（P ＜ 0.05），but had no significant correlation with serum FSH peak value（P ＞ 0.05）. Morning urine LH level was positively correlated with morning urine FSH，uterine long diameter，transverse diameter，anteroposterior diameter，uterine volume， ovarian volume，serum LH peak and FSH peak（P ＜ 0.05）. ③The area under curve（AUC），sensitivity and specificity of ROC curve when uterine artery PI，uterine long diameter，and morning urine LH were used for diagnosing CPP in girls were 0.915，76%，90%； 0.945，95% ，88% ；0.925，91% ，84% ，respectively. When uterine artery PI，uterine long diameter，and morning urine LH were combined in the diagnosis of CPP in girls，the AUC，sensitivity and specificity were 0.974，98% and 90%，respectively，which was better than used alone. Conclusion：The combined determination of uterine artery PI，uterine long diameter and morning urine LH display the highest efficacy in the diagnosis of CPP in girls，and has the advantages of safety，non -invasive and convenient，which is suitable for clinical application.

Abstract:Objective：This study aims to establish a nomogram model for predicting the risk of postoperative intracranial infection in patients with severe neurological diseases. Methods：A retrospective study was conducted on clinical data from 200 patients who underwent surgical treatment in our hospital’s neurosurgical care unit between January 2018 and January 2021. The patients were randomly divided into a training set（n=140）and a validation set（n=60）. Univariate analysis and multivariate logistic regression analysis were used to screen the risk factors，constructing the prediction model by nomogram. The receiver operating characteristic （ROC）curve was plotted to assess the predictive efficacy of the nomogram model for intracranial infection in patients with severe neurological diseases. Additionally，validation of the model and evaluation of its clinical net benefit were performed using decision curve analysis（DCA）. Results：The protopathy，external ventricular drainage time and lumbar cisterna drainage time were the risk factors for postoperative intracranial infection（P ＜ 0.05）. ROC curve of the nomogram model showed that the area under curve（AUC） of the training set and the validation set were 0.774（95% CI：0.695~0.853）and 0.831（95% CI：0.725~0.936），respectively. DCA curves showed that the prediction of intracranial infection could improve the clinical benefit rate. Conclusion：Our nomogram prediction model based on risk factors associated with postoperative intracranial infection in patients with severe neurological diseases offers an effective approach for early identification of high-risk individuals，facilitating prompt diagnosis and treatment while improving the prognosis of patients.

Abstract:The enhancer is a special class of transcriptional regulatory elements in eukaryotic genomes. There are a large number of enhancer elements in eukaryotic genomes. Enhancers can interact with the promoters of target genes through the formation of chromatin loop，and regulate the transcription of target genes together with the promoters. A large number of studies have shown that genetic variations，epigenetic modifications and abnormal transcription factors can directly or indirectly lead to enhancer dysfunction or genome enhancer remodeling that are closely correlation to the occurrence and progression of malignant tumor. In recent years，the rapid development and update of high-throughput sequencing technology and database have strongly enhanced the depth and breadth of enhancer research. In this review，we briefly introduced and summarized the structural characteristics and the regulation mode of enhancers，and the formation mechanism of abnormal regulation in the process of tumorigenesis and development，as well as the main technical means of enhancer identification and common databases.

Abstract:Tumor adoptive cellular immunotherapy is a new model of tumor immunotherapy. It can induce effective anti - tumor immune response in patients by infusion the engineered immune cells which are amplified and activated in vitro. However，due to the complex tumor immunosuppressive microenvironment，immune cells are prone to exhaust and difficult to penetrate deep into the tumor， resulting in limited effect in solid tumors. In recent years，nanomaterials have received extensive attention in the field of tumor immunotherapy. Nanomaterials can promote the expansion of immune cells，their survival after in vivo infusion，and their infiltration in tumors，help immune cells to overcome the physical barriers and immunosuppressive microenvironment in solid tumor tissues，and improve the therapeutic effect. In this article，we reviewed the current research progress of the application of nanomedicine in tumor adoptive cellular immunotherapy.

Abstract:PIWI -interacting RNAs（piRNA）are novel small -molecule non -coding RNAs that mediated by interacting with PIWI proteins. They are mainly among Droflies，mammalian（human，mouse，etc.）stem cells and germ cells. More and more studies have shown that piRNA can regulate gene expression through epigenetic changes，including transposon silencing，DNA methylation and chromatin modification，and play a key role in the occurrence of tumors. Therefore，piRNA has the potential as a biomarker to provide a new method for cancer diagnosis and prognosis monitoring. This article reviews the biological role of piRNA in colorectal cancer， providing clues for the pathogenesis of colorectal cancer and the search for its effective biomarkers.

Abstract:The liver is an important organ in the human body which is in charge of many key physiological processes，including metabolism，detoxification，and immunity. Normally，homeostasis of macrophages in the liver maintains liver function. Disruption of macrophage homeostasis，evolution among different cell subsets，and altered function contribute to the progression of non - alcoholic fatty liver diseases（NAFLD）. Single cell RNA-seq technology is used to identify specific macrophage subsets for the treatment of non- alcoholic fatty liver diseases. This article will review the classification，heterogeneity，and role of hepatic macrophages in non-alcoholic fatty liver diseases.

Abstract:Hepatitis E is an infectious disease caused by hepatitis E virus（HEV）infection，which is a significant public health concern worldwide. Although hepatitis E is generally considered an asymptomatic，self-limiting disease，its clinical manifestations vary， some patients may develop severe or chronic progression，resulting in poor prognosis and serious harm. Immune response is a key factor determining the clinical manifestation and outcome of hepatitis E. Normal immune response facilitates the clearance of virus and recovery from this disease，while excessive or disordered immune response can participate in severe and chronic progression of the disease，leading to disease progression. Through literature review，this article summarizes the immunological mechanisms of HEV related liver failure and chronic hepatitis E，including innate immune response and adaptive immune response，in order to provide theoretical basis and new ideas for early prediction，clinical prevention and treatment，and disease management.