Abnormal synaptic plasticity is an early pathological feature of Alzheimer disease (AD). Synaptic damage and dysfunction initiate neuronal degeneration and death, ultimately leading to cognitive impairment. Traditional Chinese medicine (TCM) can effectively ameliorate cognitive dysfunction through multitarget regulation of synaptic plasticity. This review summarizes the mechanisms by which TCM, including active components, single herbs, and classical formulas, modulates synaptic plasticity, offering new insights for future research and clinical applications. Relevant experimental studies published between 2020 and 2024 were retrieved from major databases, including China National Knowledge Infrastructure, the National Science and Technology Library, Wanfang Data, Elsevier, ScienceDirect, PubMed, SpringerLink, and Web of Science. Network pharmacology and bioinformatics approaches were used to predict the therapeutic effects and mechanisms of TCM on AD-related synaptic plasticity. In total, 15 TCM single herbs and 11 TCM formulas were identified as enhancing AD-related synaptic plasticity. Additionally, 15 active ingredients targeting synaptic plasticity in AD were retrieved from TCM databases over the past decade. This review provides novel perspectives and strategic directions for future AD research and therapeutic development.

Objective To investigate and compare the effects of electroacupuncture and dexamethasone on lung function and histomorphology and behavior in the offspring of perinatal nicotine exposure(PNE)rats.Methods Twenty-four pregnant Sprague-Dawley rats were randomly divided into control,model,electroacupuncture shallow needling,and dexamethasone groups using the random number table method(n=6 rats per group).A pulmonary dysplasia model in offspring rats with PNE was prepared by cervicodorsal subcutaneous injection with nicotine,and successful establishment of the model was confirmed by demonstrating statistically significant differences in growth parameters,lung function,and lung morphology compared to the control group.From the sixth day of maternal conception,the control group received cervicodorsal subcutaneous injection with 0.9%sodium chloride solution(1 mg/kg once per day),and the remaining groups were similarly injected with nicotine(1 mg/kg once per day).Concurrent with the nicotine injections,the electroacupuncture shallow needling group received electroacupuncture interventions at the"Zusanli"(ST 36)acupoint on both sides once a day for 20 min.In contrast,the offspring rats in the dexamethasone group received intraperitoneal dexamethasone injections from postnatal day 8(1.5 mg/kg once per day for 3 days),with a later dose of 0.75 mg/kg once per day for 4 days.Following successful model establishment,four offspring per rat were retained in each group using the random number table method.Until the 21st day after the birth of the offspring,using the random number table method,one offspring randomly selected from the four retained offspring per rat in each group was assigned to growth parameter assessment including body weight,lung weight,and lung index;simultaneously,one offspring was randomly selected for pulmonary function which was detected by a small animal pulmonary function machine,with the parameters of forced vital capacity(FVC),functional residual capacity(FRC),dynamic lung compliance(Cdyn),peak expiratory flow(PEF),peak inspiratory flow(PIF),and airway resistance(RL);concurrently,one offspring was randomly selected for hematoxylin and eosin staining to observe the histomorphology of the lung tissue,alveolar numbers,and mean alveolar septal thickness;additionally,one offspring was randomly selected for Morris water maze testing to evaluate the effects of the two intervention methods on learning and memory capabilities in offspring rats with PNE.Results Compared with the control group,the body weight,lung weight,lung index,FVC,PEF,FRC,Cdyn,alveolar number,platform crossing times,target quadrant time percentage,and target quadrant path percentage in the Morris water maze experiment were significantly decreased in the offspring rats of the model group(P<0.01).In contrast,PIF,RL,average thickness of alveolar septa,and latency of the Morris water maze experiment were significantly increased in the offspring rats of the model group(P<0.01).Compared with the model group,both electroacupuncture shallow needling group and dexamethasone group exhibited significant increases in body weight,lung weight,lung index,FVC,PEF,FRC,Cdyn,and alveolar numbers(P<0.05,P<0.01),along with significant decreases in PIF,RL values,and mean alveolar septal thickness(P<0.01).However,in the Morris water maze experiment,compared with the model group,the electroacupuncture shallow needling group demonstrated significantly more platform crossing times and a higher target quadrant time percentage and target quadrant path percentage(P<0.01),coupled with reduced latency period(P<0.01),whereas the dexamethasone group showed no significant differences compared to the model group.Compared to the electroacupuncture shallow needling group,the dexamethasone group showed significantly less platform crossing times and a lower target quadrant time percentage and target quadrant path percentage,coupled with increased latency period(P<0.01).Conclusion Both electroacupuncture and dexamethasone demonstrated protective effects on lung development in PNE offspring rats by ameliorating lung histomorphology and pulmonary function.However,offspring receiving late,small-dose,short-course dexamethasone exhibited inferior learning and memory capabilities,whereas the electroacupuncture group showed significantly superior cognitive performance compared to the dexamethasone group.

Objective:To screen for microRNAs(miRNAs)highly expressed in the serum exosomes(Exo)of esophageal squamous cell carcinoma(ESCC)patients and analyze their relationship with the clinicopathological characteristics of the patients,and to explore the potential of Exo-derived miRNAs as clinical auxiliary diagnostic markers for ESCC.Methods:Serum and relevant clinical data of 50 healthy subjects and 45 newly diagnosed ESCC patients admitted to the Fourth Hospital of Hebei Medical University between December 2021 and June 2023 were collected,serving as the control group and the ESCC group respectively.The Gene Expression Omnibus(GEO)database and qPCR were used to screen and identify the candidate miRNA for increased expression in the serum of ESCC patients-miR-1246.The diagnostic efficacy of serum miR-1246 for ESCC was analyzed by the receiver operating characteristic curve.The relationship between miR-1246 and the clinical feature progression of ESCC patients was analyzed by Logistic regression,and the relationship between miR-1246 and the clinicopathological characteristics of ESCC patients was analyzed by the χ2 test.Exosomes in the serum of the subjects were isolated,purified and characterized for verification.The expression of miR-1246 in Exo was detected by qPCR.ESCC KYSE150 and KYSE30 cells were routinely cultured.mimics-NC and miR-1246 mimics were transfected respectively into KYSE150 cells using Lipofectamine 2000.Inhibitor-NC and miR-1246 inhibitor were transfected into KYSE30 cells,which were respectively denoted as the minics-NC,miR-1246 mimics,inhibitor-NC and miR-1246-inhibitor groups.KYSE150 and KYSE30 cells were treated with Exo derived from KYSE150 cells in the mimics-NC and miR-1246 mimics groups.The proliferation,migration and invasion abilities of cells in each group were detected by the CCK-8 assay,scratch wound healing assay and Transwell chamber assay respectively.The expressions of Exo markers,epithelial-mesenchymal transition-related proteins,TET family methylcytosine dioxygenase 2(TET2)and cell adhesion molecule 1(CADM1)proteins in each group of cells were detected by WB assay.The targeting binding relationship between miR-1246 and TET2 and CADM1 was verified by the dual-luciferase reporter gene assay.Results:Bioinformatics screening showed that the miRNA with the most significant differential expression in the serum of ESCC patients was miR-1246.The serum Exo extracted from the patients conformed to the typical Exo characteristics.The expression level of serum Exo-miR-1246 in ESCC patients at stages Ⅰ-Ⅱ was significantly higher than that in healthy subjects(P<0.01);the level of serum Exo-miR-1246 in ESCC patients at stages Ⅲ-Ⅳ was significantly higher than that in patients at stages Ⅰ-Ⅱ(P<0.01).ROC curve analysis showed that Exo-miR-1246 in serum had a high value for auxiliary differential diagnosis of ESCC(P<0.05),and the auxiliary diagnostic efficacy of Exo-miR-1246 for the clinical progression of ESCC patients was higher than that of CEA and SCC-Ag(P<0.05).The combined detection of the three could further improve the efficacy of auxiliary diagnosis of patient staging(P<0.01).Exo-miR-1246 might be an independent risk factor for the clinical progression of ESCC patients(P<0.05).The expression level of serum Exo-miR-1246 was associated with the T-stage,N-stage and clinical stage of ESCC(P<0.01).Overexpression of miR-1246 could promote the proliferation,migration,invasion,epithelial-mesenchymal transition and inhibit apoptosis of ESCC cells,while inhibition of miR-1246 had the opposite effect.Database data analysis found that TET2 and CADM1 were the target genes of miR-1246.The dual-luciferase reporter gene assay confirmed that miR-1246 could directly bind to TET2 and CADM1 mRNA and inhibit their expressions(P<0.01).Treatment of KYSE150 and KYSE30 cells with Exo derived from cells overexpressing miR-1246 had the same effect as overexpressing miR-1246 in these cells.Conclusion:Exo-derived miR-1246 has the potential to be a clinical auxiliary diagnostic marker for ESCC.It may affect the occurrence and development of ESCC by regulating the expression levels of TET2 and CADM1.

Objective To investigate and compare the effects of electroacupuncture and dexamethasone on lung function and histomorphology and behavior in the offspring of perinatal nicotine exposure(PNE)rats.Methods Twenty-four pregnant Sprague-Dawley rats were randomly divided into control,model,electroacupuncture shallow needling,and dexamethasone groups using the random number table method(n=6 rats per group).A pulmonary dysplasia model in offspring rats with PNE was prepared by cervicodorsal subcutaneous injection with nicotine,and successful establishment of the model was confirmed by demonstrating statistically significant differences in growth parameters,lung function,and lung morphology compared to the control group.From the sixth day of maternal conception,the control group received cervicodorsal subcutaneous injection with 0.9%sodium chloride solution(1 mg/kg once per day),and the remaining groups were similarly injected with nicotine(1 mg/kg once per day).Concurrent with the nicotine injections,the electroacupuncture shallow needling group received electroacupuncture interventions at the"Zusanli"(ST 36)acupoint on both sides once a day for 20 min.In contrast,the offspring rats in the dexamethasone group received intraperitoneal dexamethasone injections from postnatal day 8(1.5 mg/kg once per day for 3 days),with a later dose of 0.75 mg/kg once per day for 4 days.Following successful model establishment,four offspring per rat were retained in each group using the random number table method.Until the 21st day after the birth of the offspring,using the random number table method,one offspring randomly selected from the four retained offspring per rat in each group was assigned to growth parameter assessment including body weight,lung weight,and lung index;simultaneously,one offspring was randomly selected for pulmonary function which was detected by a small animal pulmonary function machine,with the parameters of forced vital capacity(FVC),functional residual capacity(FRC),dynamic lung compliance(Cdyn),peak expiratory flow(PEF),peak inspiratory flow(PIF),and airway resistance(RL);concurrently,one offspring was randomly selected for hematoxylin and eosin staining to observe the histomorphology of the lung tissue,alveolar numbers,and mean alveolar septal thickness;additionally,one offspring was randomly selected for Morris water maze testing to evaluate the effects of the two intervention methods on learning and memory capabilities in offspring rats with PNE.Results Compared with the control group,the body weight,lung weight,lung index,FVC,PEF,FRC,Cdyn,alveolar number,platform crossing times,target quadrant time percentage,and target quadrant path percentage in the Morris water maze experiment were significantly decreased in the offspring rats of the model group(P<0.01).In contrast,PIF,RL,average thickness of alveolar septa,and latency of the Morris water maze experiment were significantly increased in the offspring rats of the model group(P<0.01).Compared with the model group,both electroacupuncture shallow needling group and dexamethasone group exhibited significant increases in body weight,lung weight,lung index,FVC,PEF,FRC,Cdyn,and alveolar numbers(P<0.05,P<0.01),along with significant decreases in PIF,RL values,and mean alveolar septal thickness(P<0.01).However,in the Morris water maze experiment,compared with the model group,the electroacupuncture shallow needling group demonstrated significantly more platform crossing times and a higher target quadrant time percentage and target quadrant path percentage(P<0.01),coupled with reduced latency period(P<0.01),whereas the dexamethasone group showed no significant differences compared to the model group.Compared to the electroacupuncture shallow needling group,the dexamethasone group showed significantly less platform crossing times and a lower target quadrant time percentage and target quadrant path percentage,coupled with increased latency period(P<0.01).Conclusion Both electroacupuncture and dexamethasone demonstrated protective effects on lung development in PNE offspring rats by ameliorating lung histomorphology and pulmonary function.However,offspring receiving late,small-dose,short-course dexamethasone exhibited inferior learning and memory capabilities,whereas the electroacupuncture group showed significantly superior cognitive performance compared to the dexamethasone group.

Objective:To screen for microRNAs(miRNAs)highly expressed in the serum exosomes(Exo)of esophageal squamous cell carcinoma(ESCC)patients and analyze their relationship with the clinicopathological characteristics of the patients,and to explore the potential of Exo-derived miRNAs as clinical auxiliary diagnostic markers for ESCC.Methods:Serum and relevant clinical data of 50 healthy subjects and 45 newly diagnosed ESCC patients admitted to the Fourth Hospital of Hebei Medical University between December 2021 and June 2023 were collected,serving as the control group and the ESCC group respectively.The Gene Expression Omnibus(GEO)database and qPCR were used to screen and identify the candidate miRNA for increased expression in the serum of ESCC patients-miR-1246.The diagnostic efficacy of serum miR-1246 for ESCC was analyzed by the receiver operating characteristic curve.The relationship between miR-1246 and the clinical feature progression of ESCC patients was analyzed by Logistic regression,and the relationship between miR-1246 and the clinicopathological characteristics of ESCC patients was analyzed by the χ2 test.Exosomes in the serum of the subjects were isolated,purified and characterized for verification.The expression of miR-1246 in Exo was detected by qPCR.ESCC KYSE150 and KYSE30 cells were routinely cultured.mimics-NC and miR-1246 mimics were transfected respectively into KYSE150 cells using Lipofectamine 2000.Inhibitor-NC and miR-1246 inhibitor were transfected into KYSE30 cells,which were respectively denoted as the minics-NC,miR-1246 mimics,inhibitor-NC and miR-1246-inhibitor groups.KYSE150 and KYSE30 cells were treated with Exo derived from KYSE150 cells in the mimics-NC and miR-1246 mimics groups.The proliferation,migration and invasion abilities of cells in each group were detected by the CCK-8 assay,scratch wound healing assay and Transwell chamber assay respectively.The expressions of Exo markers,epithelial-mesenchymal transition-related proteins,TET family methylcytosine dioxygenase 2(TET2)and cell adhesion molecule 1(CADM1)proteins in each group of cells were detected by WB assay.The targeting binding relationship between miR-1246 and TET2 and CADM1 was verified by the dual-luciferase reporter gene assay.Results:Bioinformatics screening showed that the miRNA with the most significant differential expression in the serum of ESCC patients was miR-1246.The serum Exo extracted from the patients conformed to the typical Exo characteristics.The expression level of serum Exo-miR-1246 in ESCC patients at stages Ⅰ-Ⅱ was significantly higher than that in healthy subjects(P<0.01);the level of serum Exo-miR-1246 in ESCC patients at stages Ⅲ-Ⅳ was significantly higher than that in patients at stages Ⅰ-Ⅱ(P<0.01).ROC curve analysis showed that Exo-miR-1246 in serum had a high value for auxiliary differential diagnosis of ESCC(P<0.05),and the auxiliary diagnostic efficacy of Exo-miR-1246 for the clinical progression of ESCC patients was higher than that of CEA and SCC-Ag(P<0.05).The combined detection of the three could further improve the efficacy of auxiliary diagnosis of patient staging(P<0.01).Exo-miR-1246 might be an independent risk factor for the clinical progression of ESCC patients(P<0.05).The expression level of serum Exo-miR-1246 was associated with the T-stage,N-stage and clinical stage of ESCC(P<0.01).Overexpression of miR-1246 could promote the proliferation,migration,invasion,epithelial-mesenchymal transition and inhibit apoptosis of ESCC cells,while inhibition of miR-1246 had the opposite effect.Database data analysis found that TET2 and CADM1 were the target genes of miR-1246.The dual-luciferase reporter gene assay confirmed that miR-1246 could directly bind to TET2 and CADM1 mRNA and inhibit their expressions(P<0.01).Treatment of KYSE150 and KYSE30 cells with Exo derived from cells overexpressing miR-1246 had the same effect as overexpressing miR-1246 in these cells.Conclusion:Exo-derived miR-1246 has the potential to be a clinical auxiliary diagnostic marker for ESCC.It may affect the occurrence and development of ESCC by regulating the expression levels of TET2 and CADM1.

Abstract: Heterologous boost COVID-19 vaccination can solved the problem of decreased efficacy caused by single dose of vaccine. Heterologous booster with adenoviral-vectored COVID-19 vaccine (Ad5-nCoV) following primary immunization with inactivated COVID-19 vaccines is a widely-used vaccination strategy in clinic, while different routes of Ad5-nCoV administration exist and pose a question which route could be more optimal. In this study, we comprehensively evaluated and compared the vaccine immunity induced in mice immunized according to three different vaccination regimens: “3×phosphate buffered solution(3× PBS)”, “2×inactivated vaccine + 1×inactivated vaccine (3×INA)”, “2×inactivated vaccine + 1×Ad5-nCoV (intramuscular)[2×INA+Ad5(im)]”and“2×inactivated vaccine + 1×Ad5-nCoV (intranasal)[2×INA+Ad5(in)]”. We found that heterologous booster with Ad5-nCoV, irrespective of the route of administration, induced significantly higher levels of anti-Spike IgG and subclasses (IgG1and IgG2c), Spike-specific T cells, class-switched Spike+ memory B cells (MBCs) than homologous booster with 3rd dose of inactivated COVID-19 vaccine. Of note, compared with the intramuscular given, intranasal given of Ad5-nCoV as a booster dose clearly induced higher levels of serum and bronchoalveolar bavage fluid anti-spike immunoglobulin A, and moreover, induced stronger infiltration of major innate effector cells like neutrophils, natural killer cells and dendritic cells into the lung tissue, which suggested that mucosal vaccine responses are generated upon intranasal booster with Ad5-nCoV. Altogether, our study analyzed the vaccine immunity induced by different COVID-19 vaccines administered using different regimens, which may guide the clinical use of other types of prophylactic vaccines aiming to mount improved vaccine responses.

Objective:To observe the protective effects of Zhiganqing Prescription on the liver of C57BL/6J non-alcoholic fatty liver disease (NAFLD) mice induced by high fat diet and its effects on PI3K/Akt/FoxO1 signaling pathway, insulin resistance (IR) and gluconogenesis.Methods:A total of 48 8-week-old male C57BL/6J mice were divided into control group ( n=8) and modeling group ( n=40) according to random number table method. The control group was fed with ordinary diet, and the model group was fed with high-fat diet. The NAFLD model was established after 8 weeks of feeding. The modeling group was divided into model group, Pioglitazone group, Zhiganqing Prescription low-, medium-, and high-dosage group ( n=8 in each group) according to random number table method, and drug intervention lasted for 8 weeks. The body mass of mice was measured regularly during administration. Fasting blood glucose (FBG) levels were measured at 0 and 8 weeks of administration, and oral glucose tolerance tests (OGTT) were conducted. After the experiment, serum levels of GPT, GOT, TC, TG, LDL-C, HDL-C, FINS and C-P were detected and HOMA-IR was calculated. The pathological morphology of liver was observed by HE and PAS staining. The expression levels of PI3K and p-Akt were detected by IHC staining. The protein expression levels of PI3K, Akt, p-Akt, FoxO1, p-FoxO1, G6PC and PCK1 were detected by Western blot. Results:Compared with model group, the body weight of mice in each administration group decreased at 4, 6 and 8 weeks ( P<0.05 or P<0.01). At the 8th week of administration, the levels of FBG and OGTT AUC in each administration group decreased ( P<0.05 or P<0.01), the levels of GPT, TC, TG and LDL-C decreased ( P<0.01), and the GOT levels in Zhiganqing Prescription medium- and high-dosage groups decreased ( P<0.01). The HDL-C level in Zhiganqing Prescription medium-dosage group decreased ( P<0.05 or P<0.01), and the HOMA-IR level in Zhiganqing Prescription low- and medium-dosage groups decreased ( P<0.05 or P<0.01). The levels of FINS and C-P in each administration group increased ( P<0.05 or P<0.01), and the expressions of PI3K protein and p-Akt/Akt, p-FoxO1 /FoxO1 protein in liver tissues increased ( P<0.05 or P<0.01). The protein expressions of G6PC and PCK1 decreased ( P<0.05 or P<0.01). Conclusion:Zhiganqing Prescription can effectively control the body mass, blood glucose, liver function and blood lipids of NAFLD mice, improve IR and gluconeogenesis, the mechanism of which may be related to the activation of PI3K/Akt/FoxO1 signaling pathway.

Ceria nanoparticles(CeO2 NPs)have become popular materials in biomedical and industrial fields due to theirpotential applications in anti-oxidation,cancer therapy,photocatalytic degradation of pollutants,sensors,etc.Many methods,including gas phase,solid phase,liquid phase,and the newly proposed green synthesis method,have been reported for the synthesis of CeO2 NPs.Due to the wide application of CeO2 NPs,concerns about their adverse impacts on human health have been raised.This review covers recent studies on the biomedical applications of CeO2 NPs,including their use in the treatment of various diseases(e.g.,Alzheimer's disease,ischemic stroke,retinal damage,chronic inflammation,and cancer).CeO2 NP toxicity is discussed in terms of the different systems of the human body(e.g.,cytotoxicity,genotoxicity,respiratory toxicity,neurotoxicity,and hepatotoxicity).This comprehensive review covers both fundamental discoveries and exploratory progress in CeO2 NP research that may lead to practical developments in the future.

OBJECTIVE: To investigate the correlation of hemoglobin (Hb) level with prognosis of elderly patients diagnosed as sepsis. METHODS: A retrospective cohort study was conducted. Information on the cases of elderly patients with sepsis in the Medical Information Mart for Intensive Care-IV (MIMIC-IV), including basic information, blood pressure, routine blood test results [the Hb level of a patient was defined as his/her maximum Hb level from 6 hours before admission to intensive care unit (ICU) and 24 hours after admission to ICU], blood biochemical indexes, coagulation function, vital signs, severity score and outcome indicators were extracted. The curves of Hb level vs. 28-day mortality risk were developed by using the restricted cubic spline model based on the Cox regression analysis. The patients were divided into four groups (Hb < 100 g/L, 100 g/L ≤ Hb < 130 g/L, 130 g/L ≤ Hb < 150 g/L, Hb ≥ 150 g/L groups) based on these curves. The outcome indicators of patients in each group were analyzed, and the 28-day Kaplan-Meier survival curve was drawn. Logistic regression model and Cox regression model were used to analyze the relationship between Hb level and 28-day mortality risk in different groups. RESULTS: A total of 7 473 elderly patients with sepsis were included. There was a "U" curve relationship between Hb levels within 24 hours after ICU admission and the risk of 28-day mortality in patients with sepsis. The patients with 100 g/L ≤ Hb < 130 g/L had a lower risk of 28-day mortality. When Hb level was less than 100 g/L, the risk of death decreased gradually with the increase of Hb level. When Hb level was ≥ 130 g/L, the risk of death gradually increased with the increase of Hb level. Multivariate Logistic regression analysis revealed that the mortality risks of patients with Hb < 100 g/L [odds ratio (OR) = 1.44, 95% confidence interval (95%CI) was 1.23-1.70, P < 0.001] and Hb ≥ 150 g/L (OR = 1.77, 95%CI was 1.26-2.49, P = 0.001) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (OR = 1.21, 95%CI was 0.99-1.48, P = 0.057). The multivariate Cox regression analysis suggested that the mortality risks of patients with Hb < 100 g/L [hazard ratio (HR) = 1.27, 95%CI was 1.12-1.44, P < 0.001] and Hb ≥ 150 g/L (HR = 1.49, 95%CI was 1.16-1.93, P = 0.002) increased significantly in the model involving all confounding factors; the mortality risks of patients with 130 g/L ≤ Hb < 150 g/L increased, while the difference was not statistically significant (HR = 1.17, 95%CI was 0.99-1.37, P = 0.053). Kaplan-Meier survival curve showed that the 28-day survival rate of elderly septic patients in 100 g/L ≤ Hb < 130 g/L group was significantly higher than that in Hb < 100 g/L, 130 g/L ≤ Hb < 150 g/L and Hb ≥ 150 g/L groups (85.26% vs. 77.33%, 79.81%, 74.33%; Log-Rank test: χ² = 71.850, P < 0.001). CONCLUSIONS Elderly patients with sepsis exhibited low mortality risk if their 100 g/L ≤ Hb < 130 g/L within 24 hours after admission to ICU, and both higher and lower Hb levels led to increased mortality risks.
Humans ; Male ; Female ; Aged ; Retrospective Studies ; Sepsis/diagnosis* ; Critical Care ; Intensive Care Units ; Prognosis ; Hemoglobins ; ROC Curve

[摘 要] 目的：检测食管鳞状细胞癌（ESCC）患者血清中高迁移率族蛋白B1（HMGB1）和吲哚胺-2，3-双加氧酶（IDO）的表达水平并探讨两者与临床病理特征及淋巴细胞亚群的相关性。方法：选取2021年3月至2022年8月在河北医科大学第四医院初次住院治疗的95例ESCC患者作为ESCC组，另选取40例健康体检人群作为对照组。ELISA法检测全部研究对象的血清HMGB1和IDO水平及不同组ESCC细胞培养上清中HMGB1、IDO和p65水平，流式细胞术检测全部研究对象外周血淋巴细胞亚群水平。WB法检测仅敲低HMGB1基因表达或敲低HMGB1后再加入NF-κB信号通路激活剂对ESCC细胞HMGB1、IDO和p65表达的影响。结果：ESCC组患者血清HMGB1和IDO水平明显高于对照组（均P<0.01）；血清HMGB1和IDO表达水平升高是ESCC临床进展的独立危险因素（均P<0.01），二者联合检测对ESCC临床进展预测价值更高（P<0.01）；血清HMGB1和IDO与ESCC患者的T分期、N分期和临床分期有明显关联（均P<0.05）； ESCC组患者血清HMGB1与外周血CD3+ T细胞、CD4+ T细胞、B细胞和NK细胞绝对计数值呈显著负相关，而与Treg细胞百分率呈显著正相关（均P<0.05），血清IDO与外周血CD3+ T细胞百分率和绝对计数值、CD4+ T细胞百分率和绝对计数值、CD8+ T细胞和B细胞绝对计数值呈显著负相关，而与Treg细胞百分率呈显著正相关（均P<0.05）；血清HMGB1和IDO表达水平呈显著正相关（P<0.01）。si-HMGB1组KYSE30和ECA109细胞及其培养上清液中IDO和p65表达水平明显低于si-NC组和si-HMGB1+PMA组（均P<0.05）。结论：血清HMGB1和IDO与ESCC临床进展和机体免疫功能密切相关，具有成为ESCC肿瘤标志物和免疫治疗新靶点的潜力。HMGB1可能通过NF-κB信号通路促进IDO表达，进行双靶点联合治疗可能会取得更好的疗效。