PARTIAL PURIFICATION AND CHARACTERIZATION OF AN AUTOCRINE T SUPPRESSOR FACTOR FROM MURINE LEUKEMIA

The leukemia-associated autoinhibitor (LAI-615) derived from murine leukemia L7811 has been investigated intensively in our laboratory. In the following experiments, the partial purification of LA I-615 has been carried out in addition to the observation of phenotype variations of L7811 leuke-mic cells. The factor was purified over 1306-fold by sequential fractionation with Sephadex G-150 gel filtration, DEAE-cellulose ion exchange chromato-graphy, and Mono Q-fast protein liquid chromato-graphy. The molecular weight of LAI-615 was 68,000 as estimated by gel filtration. LAI-615 was a protein but not glycosylated, and it was suggested LAI-615 be secreted in an autocrine manner. Im-munocytochemical staining showed that the expression of Lyt2 phenotype of L7811 leukemic cells was often coincident with the secretion of LAI-615. Moreover, the physicochemical characteristics of LAI-615 was similar to that of T suppressor factor. Thus it is concluded that LAI-615 may be one of TsF-like factors.

Changes of the immunological barrier of intestina mucosa in rats with sepsis

BACKGROUND： Sepsis has become the greatest threat to in-patients, with a mortality of over 25%.The dysfunction of gut barrier, especially the immunological barrier, plays an important role in the development of sepsis. This dysfunction occurs after surgery, but the magnitude of change does not differentiate patients with sepsis from those without sepsis. Increased intestinal permeability before surgery is of no value in predicating sepsis. The present study aimed to observe the changes of intestinal mucosal immunologic barrier in rat models of sepsis induced by cecal ligation and puncture.METHODS： Sixty Sprague-Dawley rats were randomly divided into a sepsis group （n=45） and a control group （n=15）. The rats in the sepsis group were subjected to cecal ligation and puncture （CLP）, whereas the rats in the control group underwent a sham operation. The ileac mucosa and segments were harvested 3, 6 and 12 hours after CLP, and blood samples were collected. Pathological changes, protein levels of defensin-5 （RD-5） and trefoil factor-3 （TFF3） mRNA, and lymphocytes apoptosis in the intestinal mucosa were determined. In an additional experiment, the gut-origin bacterial DNA in blood was detected.RESULTS： The intestinal mucosa showed marked injury with loss of ileal villi, desquamation of epithelium, detachment of lamina propria, hemorrhage and ulceration in the sepsis group. The expression of TFF3 mRNA and level of RD-5 protein were decreased and the apoptosis of mucosal lymphocyte increased （P〈0.05） in the sepsis group compared with the control group. Significant differences were observed in RD-5 and TFF3 mRNA 3 hours after CLP and they were progressively increased 6 and 12 hours after CLP in the sepsis group compared with the control group （P〈0.05, RD-5 F=11.76, TFF3 F=16.86 and apoptosis F=122.52）. In addition, the gut-origin bacterial DNA detected in plasma was positive in the sepsis group.CONCLUSION： The immunological function of the intestinal mucosa was impaired in septic rats and further deteriorated in the course of sepsis.

Immunological factors in cirrhosis diseases from a bibliometric point of view

BACKGROUND Cirrhosis results from persistent liver injury that leads to liver fibrosis.Immunological factors play important regulatory roles in the development and progression of cirrhosis.Bibliometrics is one of the most commonly used methods for systematic evaluation of a field of study.To date,there are no bibliometric studies on the role of immunological factors in cirrhosis.AIM To provide a comprehensive overview of the knowledge structure and research hotspots of immunological factors in cirrhosis.METHODS We retrieved publications related to immunological factors in cirrhosis between 2003 to 2022 from the Web of Science Core Collection database on December 7,2022.The search strategy was TS=((Liver Cirrhosis OR hepatic cirrhosis OR liver fibrosis)AND(Immunologic*Factor*OR Immune Factor*OR Immunomodulator*OR Biological Response Modifier*OR Biomodulator*)).Only original articles and reviews were included.A total of 2873 publications were analyzed using indicators of publication and citation metrics,countries,institutes,authors,journals,references,and keywords by CiteSpace and VOSviewer.RESULTS A total of 5104 authors from 1173 institutions across 51 countries published 2873 papers on cirrhosis and immunological factors in 281 journals.In the past 20 years,the increasing number of related annual publications and citations indicates that research on immunological factors in cirrhosis has become the focus of attention and has entered a period of accelerated development.The United States(781/27.18%),China(538/18.73%),and Germany(300/10.44%)were the leading countries in this field.Most of the top 10 authors were from the United States(4)and Germany(3),with Gershwin ME contributing the most related articles(42).World Journal of Gastroenterology was the most productive journal,whereas Hepatology was the most co-cited journal.Current research hotspots regarding immunological factors in cirrhosis include fibrosis,cirrhosis,inflammation,liver fibrosis,expression,hepatocellular carcinoma,activation,primary biliary cirrhosis,disease,and hepatic stellate cells.Burst keywords(e.g.,epidemiology,gut microbiota,and pathways)represent research frontiers that have attracted the interest of researchers in recent years.CONCLUSION This bibliometric study comprehensively summarizes the research developments and directions of immunological factors in cirrhosis,providing new ideas for promoting scientific research and clinical applications.

Immunological disturbance effect of exogenous histamine towards key immune cells

Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk.However,its influences on immunological components,especially the function of key immune cells,are still poorly known.In this work,we explored the effects of exogenous histamine on the function of key immune cells such as intestinal epithelial cells,dendritic cells,and T cells.The results showed that histamine could affect the expression of allergy-related genes in CMT93 cells at a high dose of histamine.Moreover,it’s found that histamine could cause an imbalance in the levels of relevant immune factors secreted by dendritic cells and T cells,especially those related to allergy.At the same time,the proportion of MHC class IIpositive dendritic cells and the proportion of T helper 2(Th2)cells in CD4^(+)T cells increased after histamine stimulation.We concluded that the presence of a certain level of histamine in food may affect the expression of allergy-related cytokines,disrupt the balance of the immune homeostasis,and potentially lead to adverse immune reactions.This work demonstrated the importance of including the estimation of histamine’s immune safety in aquatic products rather than merely considering the potential risk of food poisoning.

Inactivation of the tumor suppressor Krüppel-like factor 6 (KLF6) by mutation or decreased expression in hepatocellular carcinomas

Background and aim： The Krueppel-like transcription factor KLF6 is a novel tumor-suppressor gene. It was inactivated in human prostate cancer and other tumors tissue, as the result of frequent mutation and loss of heterozygosity （LOH）. However, there is no data reporting the levels of KLF6 both mRNA and protein in hepatocellular carcinomas （HCCs）. We therefore detected mutations and expression of KLF6 in HCC tissues and further observed the effect of it on cell growth in HCC cell lines. Methods： We analyzed the exon-2 ofKLF6 gene by direct DNA sequencing, and detected the expression of KLF6 by RT-PCR and Western blot in 23 HCC tissues and corresponding nontumorous tissues. Loss of growth suppressive effect of the HCC-derived KLF6 mutant was characterized by in vitro growth curves plotted, flow cytometry and Western blotting. Results： KLF6 mutations were found in 2 of 23 HCC tissues and one of mutations was missense. Expression ofKLF6 mRNA or protein was down-regulated in 8 （34.7%） or 9 （39.1%） of 23 HCC tissues. Wild-type KLF6 （wtKLF6） inhibited cellular proliferation and prolonged G1 -S transition by inducing the expression of p21WAF 1 following stable transfection into cultured HepG2 cells, but tumor-derived KLF6 mutant （mKLF6） had no effects. Conclusion： Our findings suggest that KLF6 may be involved in pathogenesis of HCC.

Heat shock factor 1 promotes neurite outgrowth and suppresses inflammation in the severed spinal cord of geckos

The low intrinsic growth capacity of neurons and an injury-induced inhibitory milieu are major contributo rs to the failure of sensory and motor functional recovery following spinal cord injury.Heat shock transcription factor 1(HSF1),a master regulator of the heat shock response,plays neurogenetic and neuroprotective roles in the damaged or diseased central nervous system.However,the underlying mechanism has not been fully elucidated.In the present study,we used a gecko model of spontaneous nerve regeneration to investigate the potential roles of gecko HSF1(gHSF1) in the regulation of neurite outgrowth and inflammatory inhibition of macrophages following spinal cord injury.gHSF1 expression in neurons and microglia at the lesion site increased dramatically immediately after tail amputation.gHSF1 ove rexpression in gecko primary neuro ns significantly promoted axonal growth by suppressing the expression of suppressor of cytokine signaling-3,and fa cilitated neuro nal survival via activation of the mitogen-activated extracellular signal-regulated kinase/extracellular regulated protein kinases and phosphatidylinositol 3-kinase/protein kinase B pathways.Furthermore,gHSF1 efficiently inhibited the macrophagemediated inflammatory response by inactivating 1kappa B-alpha/NF-kappaB signaling.Our findings show that HSF1 plays dual roles in promoting axonal regrowth and inhibiting leukocyte inflammation,and provide new avenues of investigation for promoting spinal co rd injury repair in mammals.

Amplification of Functional Myeloid-derived Suppressor Cells during Stem Cell Mobilization Induced by Granulocyte Colony-stimulation-factor

The effects of granulocyte colony-stimulation-factor （G-CSF） on stem cell mobilization and its impact on the amplification of myeloid-derived suppressor cells （MDSCs） of donor mice were ex- amined. A mouse model of stem cell mobilization was established by consecutive subcutaneous injec- tion of 100 μg/kg G-CSF for 5 days. The blood from the donor mice was routinely examined during mobilization. Stem cells and MDSCs were analyzed by flow cytometry. The immunosuppressive mole- cules derived from MDSCs in serum and spleen, including hydrogen dioxide （H202） and nitric oxide （NO）, and the activity of nitric oxide synthase （NOS） were determined during the mobilization. Apop- tosis of T lymphocytes was assessed by using Annexin-V/PI. During stem cell mobilization, the number of lymphocytes and white blood cells in the peripheral blood was increased, and peaked on the 4th day. The number of stem cells in G-CSF-treated mice was significantly greater than that in controls （P〈0.01）. The expansions of MSDCs were also observed after G-CSF mobilization, with a more notable rate of growth in the peripheral blood than in the spleen. The activity of NOS and the production of NO were increased in the donor mice, and the serum H202 levels were approximately 4-fold greater than the con- trois. Consequently, apoptosis of T lymphocytes was increased and showed a positive correlation with the elevated percentage of MDSCs. It was concluded that G-CSF could provide sufficient peripheral blood stem cells for transplantation. Exogenous administration of G-CSF caused the accumulation of MDSCs in the peripheral blood and the spleen, which could lead to apoptosis ofT lymphocytes and may offer a new strategy for the prevention and treatment of graft versus host disease.

Correlation research of Runt-related transcription factor 2 with proliferation genes, tumor suppressor genes and angiogenesis molecules in colon cancer lesions

Objective: To investigate the correlation of Runt-related transcription factor 2 (RunX2) with proliferation genes, tumor suppressor genes and angiogenesis molecules in colon cancer lesions. Methods: A total of 90 patients with primary colon cancer were enrolled in colon cancer group, 68 patients with benign colon polyps were enrolled in colon polyps group, the differences in the expression levels of RunX2, proliferation genes, tumor suppressor genes and angiogenesis molecules in the two groups of lesions were compared, and Pearson test was further used to evaluate the correlation of RunX2 expression level with proliferation gene, tumor suppressor gene and angiogenesis molecule expression levels in colon cancer tissues. Results: RunX2 mRNA expression level in the lesions of colon cancer group was higher than that of colon polyps group. Proliferation genes GTPBP4, HOXB7, ZNF331, ADAM17 and HSP60 mRNA expression levels in the lesions of colon cancer group were higher than those of colon polyps group;tumor suppressor genes ATF3, FOXN3, OTUD1 and NDRG2 mRNA expression levels were lower than those of colon polyps group;angiogenesis molecules Musashi 1, NF-κB, RegⅣ and STAT3 mRNA expression levels were higher than those of colon polyps group. RunX2 mRNA expression level in the colon cancer lesions was directly correlated with the expression levels of the above proliferation genes, tumor suppressor genes and angiogenesis molecules. Conclusion: RunX2 expression is abnormally high in colon cancer lesions, the specific expression level is positively correlated with cancer cell proliferation activity and angiogenesis activity, and it is an important molecular target that can lead to the occurrence and development of colon cancer.

T淋巴细胞、炎症细胞因子与卵巢子宫内膜异位症的相关性及诊断价值

目的探讨外周血中T淋巴细胞、炎症细胞因子与卵巢子宫内膜异位症(OMs)的相关性及诊断价值。方法选取2020年10月—2022年6月我院收治行开腹或腹腔镜手术经病理确诊OMs患者72例为观察组,根据修正子宫内膜异位症分期(r-AFS)分为I~II期37例,III~IV期35例,另选取同期术后诊断为单纯性卵巢囊肿或良性畸胎瘤的患者72例为对照组。利用流式细胞检测法检测外周血中T淋巴细胞(CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+))、炎症细胞因子(IL-2、IL-4、IL-6、IL-10、IL-17A、IFN-γ和TNF-α含量),收集相关临床资料进行单因素及Logistic多因素回归分析讨论OMs影响因素,I~II、III~IV期EMs患者中比较外周血独立影响指标CD4^(+)、TNF-α表达差异。ROC曲线评估CD4^(+)、CD8^(+)和TNF-α3项指标单独及联合对OMs的诊断效能。结果CD8^(+)、IL-2、IL6、IL-10、TNF-α、月经初潮年龄<13岁,经期天数>6天、痛经、人流手术或宫腔操作史和剖宫产史为OMs危险因素,CD4^(+)及CD4^(+)/CD8^(+)为OMs保护因素;CD8^(+)、TNF-α、经期天数>6天、痛经和人流手术或宫腔操作史为OMs独立危险因素,CD4^(+)为OMs独立保护因素;I~II、III~IV期OMs CD4^(+)、CD8^(+)和TNF-α差异有统计学意义(P<0.05);CD4^(+)、CD8^(+)与TNF-α联合检测可提高OMs诊断效能。结论外周血T淋巴细胞亚群、炎症细胞因子在OMs发生中发挥着一定作用,CD4^(+)、CD8^(+)和TNF-α参与疾病进展且3者联合检测在OMs诊断方面可能具有较高应用价值。

基于骨免疫学论中医药抑制类风湿关节炎骨破坏的研究进展

类风湿关节炎(RA)是一种以滑膜炎、软骨与骨破坏为主要病理表现的自身免疫性疾病,致残率较高。RA免疫及炎症反应与骨细胞代谢互为影响,其核心环节为破坏机体核因子κB受体活化因子配体/核因子κB受体活化因子/骨保护素(RANKL/RANK/OPG)信号通路的平衡,导致成骨细胞减少,以及破骨细胞凋亡减退及异常活化。西药目前以抑制炎症反应及相关细胞因子分泌,减缓疾病进展,但长期使用其不良反应难以忽视。中医药在防治骨破坏中研究逐步深入,但在基础及临床研究方面仍存在一定局限性。

烧山火针刺法联合甲氨蝶呤治疗类风湿关节炎活动期的效果及其对患者炎症因子和免疫功能的影响

目的 观察烧山火针刺法联合甲氨蝶呤治疗类风湿关节炎(RA)活动期的效果,并探讨其抗炎和调节免疫作用机制。方法 选取2020年2月至2022年10月郑州市第一人民医院收治的60例RA活动期患者纳入研究,按照随机数表法分为常规组和联合组各30例。常规组患者给予甲氨蝶呤治疗,联合组患者给予烧山火针刺法联合甲氨蝶呤治疗,均治疗两周。于治疗两周后比较两组患者的治疗效果,以及治疗前后的中医证候评分、28个关节疾病活动(DAS28)评分、疼痛(VAS)评分、炎性指标[血沉(ESR)、C反应蛋白(CRP)、肿瘤坏死因子-α (TNF-α)、类风湿因子(RF)、抗环瓜氨酸肽(CCP)抗体]、免疫指标(Treg细胞、Th17细胞、Treg/Th17细胞),同时比较两组患者治疗期间的不良反应发生情况。结果 联合组患者的治疗总有效率为93.33%,明显高于常规组的73.33%,差异有统计学意义(P<0.05);联合组患者治疗两周后的中医证候关节肿胀、冷痛、压痛、晨僵、屈伸不利评分分别为(0.72±0.18)分、(0.70±0.20)分、(0.81±0.22)分、(0.68±0.15)分、(0.77±0.19)分,明显低于常规组的(1.03±0.24)分、(0.96±0.23)分、(1.14±0.26)分、(0.91±0.21)分、(1.09±0.23)分,差异均有统计学意义(P<0.05);联合组患者治疗两周后的DAS28、VAS评分分别为(2.18±0.33)分、(2.46±0.22)分,明显低于常规组的(3.26±0.47)分、(2.89±0.27)分,差异均有统计学意义(P<0.05);联合组患者治疗两周后的ESR、抗CCP抗体、RF、CRP、TNF-α水平分别为(16.23±2.29) mm/h、(172.30±30.14) IU/mL、(130.85±15.42) IU/mL、(10.20±1.68) mg/L、(18.95±4.38) pg/mL,明显低于常规组的(21.84±3.41) mm/h、(205.68±36.77) IU/mL、(157.62±24.10) IU/mL、(13.65±2.06) mg/L、(24.51±6.02) pg/mL,差异均有统计学意义(P<0.05);联合组患者治疗两周的外周血Treg细胞百分比、Treg/Th17比值分别为(2.61±0.35)%、2.44±0.37,明显高于常规组的(2.17±0.28)%、1.68±0.32,Th17细胞百分比为(1.07±0.18)%,明显低于常规组的(1.29±0.22)%,差异均有统计学意义(P<0.05);两组患者治疗期间的不良反应发生率差异无统计学意义(P>0.05)。结论 烧山火针刺法联合甲氨蝶呤治疗RA活动期能明显减轻患者的临床症状,降低炎症反应,调节免疫功能,临床应用疗效显著,且安全性良好。

慢性免疫性血小板减少症患者BLyS及其受体BAFF-R与血清免疫学指标的相关性

目的探讨慢性免疫性血小板减少症(ITP)患者B淋巴细胞刺激因子(BLyS)及其受体B淋巴细胞刺激因子受体(BAFF-R)与血清免疫学指标的相关性。方法纳入内蒙古医科大学附属医院血液科2020年1月-2022年1月住院的ITP患者50例行回顾性分析,将其设为观察组,另选取同期本院体检中心接诊的50例健康体检者,将其设为对照组。检测并比较两组血清BLyS、BAFF-R、免疫学指标。将观察组患者按疾病严重程度分为轻度组(11例)、中度组(29例)、重度组(10例),比较不同严重程度组血清BLyS、BAFF-R、免疫学指标;ITP患者均给予地塞米松、丙种球蛋白、泼尼松等对症治疗,比较预后不良组、预后良好组血清BLyS、BAFF-R、免疫学指标,Pearson分析BLyS、BAFF-R与免疫学指标的相关性,绘制受试者工作曲线(ROC),计算曲线下面积(AUC),分析BLyS、BAFF-R、免疫学指标对ITP患者预后不良的预测效能。结果观察组血清BLyS、BAFF-R、外周血IgG、IgA、IgM均高于对照组(P<0.05)。重度组血清BLyS、BAFF-R、外周血IgG、IgA、IgM均高于中度组、轻度组(P<0.05)。预后不良组血清BLyS、BAFF-R、外周血IgG、IgA、IgM均高于预后良好组(P<0.05)。BLyS、BAFF-R与IgG、IgA、IgM均呈正相关性(P<0.05)(r值=4.034、3.986、4.134、3.964、4.006、4.086)。BLyS、BAFF-R、IgG、IgA、IgM联合检测预测ITP预后不良的AUC是0.801(95%CI:0.734~0.959),灵敏度、特异度分别是93.62%、90.24%,均高于单独检测(P<0.05)。结论ITP患者BLyS及其受体BAFF-R表达量随着疾病的加重会逐渐增高,与血清免疫学指标IgG、IgA、IgM均呈正相关性,联合检测可提高对预后不良的预测灵敏度及特异度,具有一定的参考价值。

雄激素受体在肿瘤中的作用及机制研究进展

雄激素受体(androgen receptor, AR)是类固醇核受体超家族的成员之一。AR在正常生理和代谢过程以及在肿瘤等多种疾病的发生与发展中起着重要作用。AR在不同肿瘤中作用不同,如在前列腺癌、黑色素瘤及胃癌等肿瘤中发挥促进作用,而在雌激素受体阳性乳腺癌中发挥肿瘤抑制作用。AR通过调节免疫(抑制肿瘤浸润性CD8^(+)T细胞的活性和干性)间接发挥促进肿瘤发生发展。该文回顾并总结AR在肿瘤中的主要作用、分子机制与最新研究进展,阐明AR的研究前景,为AR的进一步研究提供思路。

原因不明复发性流产诊治及临床研究进展

复发性流产(recurrent spontaneous abortion,RSA)是目前常见的一种早期妊娠并发症,在近50%的病例中,RSA的病因仍然不明,这类病例通常被称为原因不明的复发性流产(unexplained recurrent spontaneous abortion,URSA)或特发性复发性流产。通过在PubMed上检索近十年来的相关研究,总结URSA疾病妇女发生流产事件的影响因素和机制,此外,还总结了现有临床实验诊断技术和治疗方法,探讨不同治疗之间的差异性与局限性,以及在未来临床研究过程中须待解决的问题和重要的优先事项。

枢经推拿对脊髓神经结扎大鼠模型炎症反应及SOCS1、TLR4蛋白表达的影响

目的本研究旨在探讨枢经推拿对神经病理性疼痛(NP)的抑炎镇痛机制。方法30只SPF级SD大鼠随机分为正常组、模型组、推拿组、假推拿组、假手术组,每组6只。除了正常组不进行处理,假手术组暴露L5神经外,其余3组大鼠采用脊神经结扎(SNL)法建立NP大鼠模型。造模后第1天开始,推拿组给予枢经推拿治疗,假推拿组给予抚摸,持续干预7 d,在造模前1 d及造模后1 d、3 d、7 d检测各组大鼠热痛缩足反应潜伏期(PWL)和机械性刺激缩足反应阈值(PWT)。干预7 d后,采用Western blot检测大鼠脊髓背角中细胞因子信号转导抑制因子1(SOCS1)、Toll样受体4(TLR4)、核因子κB(NF-κB)表达水平,采用ELISA检测脊髓背角组织白细胞介素6(IL-6)水平。结果造模前1 d,各组大鼠的PWT、PWL没有显著差异(P>0.05);造模后1 d、3 d、7 d,与正常组、假手术组相比,假推拿组、推拿组、模型组大鼠的PWT、PWL均降低(P<0.05),且造模后3 d和7 d,与模型组、假推拿组相比,推拿组大鼠的PWT、PWL均升高(P<0.05)。与正常组、假手术组相比,假推拿组、推拿组、模型组大鼠的SOCS1蛋白水平均明显升高(P<0.05);推拿组大鼠与模型组、假推拿组相比,SOCS1水平升高(P<0.05)。与正常组、假手术组相比,假推拿组、推拿组、模型组大鼠的脊髓背角TLR4、NF-κB、IL-6水平明显增加(P<0.05);与模型组相比,推拿组大鼠的TLR4、NF-κB、IL-6水平明显降低(P<0.05)。结论枢经推拿可以改善由SNL诱导的NP,其机制可能与通过上调脊髓背角中SOCS1蛋白表达,负反馈下调TLR4及NF-κB蛋白表达,降低促炎因子IL-6产生有关。

维生素D缺乏患者血清25羟维生素D水平与M-MDSCs、TNF-α、IL-10的差异性分析

目的探讨维生素D缺乏患者血清25羟维生素D[25(OH)D]水平与单核细胞型髓源抑制性细胞(M-MDSCs)、肿瘤坏死因子-α(TNF-α)和白细胞介素-10(IL-10)的相关性。方法选取2022年6—9月于银川市第一人民医院就诊的维生素D缺乏症患者24例(维生素D缺乏组)和同期健康体检者24例(正常对照组),收集基础临床指标,采集外周抗凝血,分离外周血浆和血细胞后,提取外周血单个核细胞(PBMCs),采用流式细胞术分析CD45+白细胞和CD45^(+)CD15^(-)CD11b^(+)HLA^(-)DR^(-)CD14^(+)M-MDSCs,采用ELISA法检测外周血清TNF-α、IL-10水平,采用Pearson相关分析探讨血清25(OH)D与M-MDSCs、TNF-α及IL-10的相关性。结果与正常对照组相比,维生素D缺乏组患者外周血白细胞增加、M-MDSCs增高(P均<0.05),血浆中TNF-α水平升高、IL-10降低(P均<0.05)。相关性分析结果显示,25(OH)D与CD45^(+)白细胞、M-MDSCs和TNF-α呈负相关,与IL-10呈正相关(P均<0.05)。结论维生素D缺乏患者25(OH)D水平降低后可促进炎症发生,并与M-MDSCs密切相关。

Studies of Hepatitis B Virus-Specific Transfer Factor reparation

制备一种乙型肝炎病毒特异性转移因子制剂 (HBV STF) ,为临床应用提供有价值的实验依据。从人HBsAg阳性胎盘中制备了HBV STF ,并对其理化性质、免疫学活性进行了检测和初步的临床试用。每批样品经无菌试验、热原质检查、动物安全性试验等均符合药典要求。本品最大紫外吸收光谱在 2 5 6± 2nm处 ,E2 60nm/E2 80nm比值大于 2 7。其水解氨基酸含 17种。对人T淋巴细胞E受体的激活试验结果显示 ,HBV STF的Ea RFc平均增高率在 83 47%～ 10 3 48%之间 ,抗原特异性皮肤试验表明HBV STF能刺激小鼠体内T淋巴细胞增殖 ,诱导小鼠跖趾部皮肤的迟发性变态反应。对HBV STF的初步临床试用也取得明显效果 ,显示HBV STF是一种可用于治疗乙肝的安全。

免疫治疗联合抗血管生成治疗在晚期非小细胞肺癌患者中的应用效果

目的探讨免疫治疗联合抗血管生成治疗在晚期非小细胞肺癌(NSCLC)患者中的应用效果。方法依据治疗方法的不同将82例晚期NSCLC患者分为观察组(n=49)和对照组(n=33),两组均给予化疗,在此基础上,对照组患者接受抗血管生成药物贝伐珠单抗治疗,观察组患者接受卡瑞利珠单抗联合贝伐珠单抗治疗。比较两组患者的临床疗效、T淋巴细胞亚群(CD3+、CD4+、CD4+/CD8+)、炎性因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)]、生活质量[卡氏功能状态(KPS)评分]及不良反应发生情况。结果观察组患者的客观缓解率为34.69%,高于对照组患者的12.12%(P﹤0.05),疾病控制率为87.76%,高于对照组患者的66.67%(P﹤0.05)。治疗后,两组患者CD3+、CD4+水平和CD4+/CD8+均高于本组治疗前,观察组患者CD3+、CD4+水平和CD4+/CD8+均高于对照组,差异均有统计学意义(P﹤0.05)。治疗后,两组患者TNF-α、IL-6水平均低于本组治疗前,KPS评分均高于本组治疗前,观察组患者TNF-α、IL-6水平均低于对照组,KPS评分高于对照组,差异均有统计学意义(P﹤0.05)。两组患者不良反应发生率比较,差异均无统计学意义(P﹥0.05)。结论免疫治疗联合抗血管生成治疗对晚期NSCLC的治疗效果较好,可改善机体免疫功能,减轻炎症反应,提高生活质量,安全性相对较高。

CTNNB1、TP53蛋白在儿童肝母细胞瘤组织中的表达及与病理特征、预后的关系

目的 探讨钙黏蛋白相关蛋白(cadherin associated protein beta 1,CTNNB1)、肿瘤抑制因子P53(tumor suppressor factor P53,TP53)蛋白在儿童肝母细胞瘤(hepatoblastoma, HB)组织中的表达及与病理特征、预后的关系。方法 选取2017-06/2020-06月作者医院收治的72例HB患儿为研究对象,手术留取癌组织标本及对应的癌旁组织。连续随访3年,记录患儿的预后生存情况,并计算总生存率(overall survival, OS)。采用免疫组织化学法检测CTNNB1、TP53蛋白在HB患儿癌组织及癌旁组织中的表达情况;采用χ~2检验分析CTNNB1、TP53蛋白表达与HB患儿临床病理特征的关系;采用多因素Cox回归分析探讨HB患儿预后的影响因素。结果 HB患儿癌组织中CTNNB1阳性表达率(76.39%)高于对照组(43.06%),TP53阴性表达率(70.83%)高于对照组(38.89%)(P均<0.05)。初诊甲胎蛋白浓度≥100μg/L、POST-TEXT分期Ⅲ~Ⅳ期、肿瘤直径≥3 cm、有肿瘤侵袭或转移HB患儿的CTNNB1阳性表达率、TP53阴性表达率高于初诊甲胎蛋白<100μg/L、POST-TEXT分期Ⅰ~Ⅱ期、肿瘤直径<3 cm、无肿瘤侵袭或转移HB患儿(P均<0.05)。初诊甲胎蛋白≥100μg/L、POST-TEXT分期Ⅲ~Ⅳ期、有肿瘤侵袭或转移、CTNNB1阳性表达、TP53阴性表达的HB患儿3年OS低于初诊甲胎蛋白<100μg/L、POST-TEXT分期Ⅰ~Ⅱ期、无肿瘤侵袭或转移、CTNNB1阴性表达、TP53阳性表达的HB患儿(P均<0.05)。多因素Cox回归分析结果显示,POST-TEXT分期Ⅲ~Ⅳ期(HR=2.077,95%CI:1.423~3.032)、有肿瘤侵袭或转移(HR=2.291,95%CI:1.536~3.417)、CTNNB1阳性表达(HR=2.757,95%CI:1.781~4.268)、TP53阴性表达(HR=2.477,95%CI:1.635~3.753)是HB患儿预后的独立危险因素(P<0.05)。结论 HB患儿癌组织中CTNNB1主要呈阳性表达,而TP53主要呈阴性表达,二者与初诊甲胎蛋白、POST-TEXT分期、肿瘤直径、有肿瘤侵袭或转移密切相关,有望作为评估HB患儿预后的生物学指标。

Intermittent fasting boosts antitumor immunity by restricting CD11b^(+)Ly6C^(low)Ly6G^(low) cell viability through glucose metabolism in murine breast tumor model

Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.