论著

母细胞性浆细胞样树突细胞肿瘤临床病理特征分析

Analysis of clinicopathological features of blastic plasmacytoid dendritic cell neoplasm and literature review

:30-34
 
目的 学习母细胞性浆细胞样树突细胞肿瘤(BPDCN)的临床病理及免疫表型特征,总结该少见肿瘤的病理诊断经验。方法 回顾分析2例BPDCN患者临床资料,通过苏木素-伊红(HE)染色分析肿瘤组织及细胞形态,通过免疫组织化学染色分析肿瘤免疫表型,通过流式细胞学检测骨髓有无肿瘤侵犯,并结合文献分析。结果 本报道中1例为97岁女性,临床以皮肤瘀斑结节为首发症状,肿瘤细胞真皮内弥漫浸润,不侵犯表皮,细胞中等大小,核形不规则,核仁不明显。另1例为69岁男性,临床以淋巴结肿大为首发症状,淋巴结结构完全破坏,肿瘤细胞弥漫浸润,细胞呈中等大小的母细胞样,核仁明显。2例免疫表型均表达CD123、CD4、CD56、TDT,不表达B系、T系淋巴细胞及髓系标志物,肿瘤均累及骨髓。结论 BPDCN是一种罕见的淋巴造血肿瘤,临床常以皮肤病变或淋巴结肿大为首发症状,临床过程具高度侵袭性,通常伴有骨髓侵犯。该肿瘤需与具有母细胞形态的淋巴系肿瘤和白血病相鉴别,诊断需结合临床信息、HE形态及免疫组化结果综合判断。
Objective To summarize the diagnostic experiences of blastic plasmacytoid dendritic cell neoplasm (BPDCN) based on the study of its clinicopathological features and immunophenotypes. Methods The clinical data of 2 patients with BPDCN were collected, the structure alteration and cell morphology were observed by HE staining, the immunophenotype of tumor cells were studied by immunohistochemistry staining and flow cytometry was adopted to confirm the bone marrow involvement. Results Two patients, one of whom was a 97 year-old female, presented with cutaneous ecchymosis nodules as the first symptom. The epidermis, but not the dermal, was diffusedly infiltrated by tumor cells, which were medium-sized with irregular nuclei without prominent nucleoli. The other case was a 69 year-old male with lymph node enlargement as the first symptom. The skin was normal, but the lymph nodes were invasively destroyed by tumor cells, which were medium-sized blast-like with prominent nucleoli. The immunophenotypes of the two patients were both positive for CD123, CD4, CD56 and TDT, but negative for B, T lymphocyte derived and myeloid origin markers, both of which involved bone marrow. Conclusions BPDCN is a rare form of hematological neoplasm, skin symptoms or lymph node enlargement may be presented as the initial symptom, the clinical course were highly aggressive with high frequency of bone marrow involvement. The blastic-like lymphoma and leukemia entities should be considered into account for differential diagnose. The precise diagnosis of BPDCN should be established by integrating histomorphology, immunophenotype and clinical presentation information comprehensively.
论著

回顾性分析非手术输血患儿红细胞恢复的影响因素

Retrospective analysis of influencing factors of RBCs recovery in children with non-surgical blood transfusion

:34-39
 
目的 调查儿科急诊非急诊手术患儿输血后红细胞恢复的影响因素。方法 回顾2020年1月—2020年12月期间广州市妇女儿童医疗中心珠江新城院区儿科急诊1月~18岁患儿的输血情况,其中分为Hb提升达预期组(n=93),Hb提升未达预期组(n=156),根据年龄、性别、体质量、是否恶性肿瘤、是否发热、有无延迟输血、输血前血红蛋白水平、输注红细胞类型情况,分析输血疗效及影响因素。结果 2组患儿的性别、年龄、体质量、有无恶性肿瘤、是否发热、输血等待时间、输血前后血红蛋白值、输注红细胞悬液量以及有无及时输血均无统计学差异;输注红细胞类型组间存在显著差异,Hb提升未达预期组更多输注了洗涤红细胞悬液(13.5% vs 5.4%,P=0.044),输血后 Hb 值较低(中位数,73 g/L vs 84 g/L,P<0.001),变化 Hb 值较小(中位数,18 g/L vs 30 g/L,P<0.001),归因分析未发现影响因素。结论 输注洗涤红细胞可能是降低输血后红细胞提升的影响因素,输注洗涤红细胞时需严格输血指征同时注意红细胞提高预值的设定。
Objective To investigate the influencing factors of blood transfusion efficacy in patients without emergency operations in pediatric emergency.Methods A retrospective analysis of the blood transfusion of pediatric emergency children(1 month~ 18 year of age)in Zhujiang New Town Branch of Guangzhou Women and Children's Medical Center from January 2020 to December 2020 was carried out,patients were divided into Hb elevation up to expectation group(n=93)and Hb elevation not up to expectation group(n=156).The efficacy of blood transfusion and the factors affecting it were analyzed according to age,gender,body mass,with or without malignant tumor,whether fever was present,whether there was delayed transfusion,pre-transfusion hemoglobin level,and the type of red blood cells transfused.Results There were no significant differences in gender,age,weight,malignant tumor,fever,waiting time for blood transfusion,hemoglobin level before and after blood transfusion,infusion volume of red blood cell suspension and whether had timely blood transfusion between the two groups.Significant differences were found between groups of transfused red blood cell types,with more washed red blood cell suspensions transfused in the Hb elevation not meeting expectations group(13.5% vs 5.4%,P=0.044),which had lower post-transfusion Hb values(median,73 g/L vs 84 g/L,P<0.001),and smaller change Hb values(median,18 g/L vs 30 g/L,P<0.001),and attribution analysis did not reveal influencing factors.Conclusions Transfusion of washed red blood cell may be an influencing factor that reduces the RBCs elevation after transfusion.Attention should be paid to strict indications for washed red blood cell transfusion and setting the expected Hb level.
专家综述

纳米药物重编程肿瘤相关巨噬细胞增强抗癌效果

Recent progress of nanoparticle reprogramming of tumor-associated macrophages(TAMs)to enhance anti-tumor activity

:1-13
 
肿瘤相关巨噬细胞(TAMs)是肿瘤微环境中最丰富的免疫细胞之一,M2-TAMs在肿瘤发生、发展、转移和治疗过程中发挥重要作用,被认为是肿瘤治疗中的重要靶点。已有的研究表明,通过将促肿瘤的M2-TAMs重编程为促炎的M1-TAMs可实现抑制肿瘤生长和转移。本综述在介绍TAMs与肿瘤治疗相关背景的基础上,重点关注纳米药物重编程TAMs增强抗肿瘤的研究进展。本文将从TAMs靶向递送各种活性物质进行重编程TAMs和纳米药物介导的异常肿瘤微环境调节的间接重编程TAMs两种方式,综述近年来基于纳米药物递送系统的调控策略及典型例子。
Tumor associated macrophages(TAMs)is one of the most abundant immune cells in the tumor microenvironment.M2-TAMs play an important role in tumor genesis,progression,metastasis and treatment,and is additionally a very important target in tumor therapy.Previous studies have shown that inhibition of tumor growth and metastasis can be achieved by reprogramming M2-TAMs to M1-TAMs.On the basis,this review focuses on the analysis progress of nano-drug reprogramming TAMs to boost anti-tumor.In this paper,we reviewed two methods of reprogramming TAMs for targeted delivery of various active substances and indirect reprogramming TAMs for abnormal tumor microenvironment regulation mediated by nanomedicine.The regulatory strategies and typical samples of nanomedicine delivery systems in recent years were summarized.
论著

MSCT增强扫描期相及VOI的选择在基于影像组学方法预测原发性肝细胞癌微血管侵犯中的价值

The value of contrast-enhanced MSCT with phases and VOI strategies in the prediction of microvascular invasion in primary hepatocellular carcinoma based on radiomics

:36-43
 
目的 基于影像组学方法,探讨多层螺旋CT(MSCT)四期增强扫描单一/不同期相及不同容积感兴趣区(VOI)的选择,在术前预测原发性肝细胞癌(HCC)微血管侵犯(MVI)中的价值。方法 回顾性收集88例经手术病理证实为HCC并行术前MSCT四期增强扫描的患者,其中包括47例MVI阳性患者和41例MVI阴性患者。在MSCT增强扫描的动脉早期、动脉晚期、门静脉期及延迟期图像中手动逐层勾画肿瘤ROI,获得瘤体容积感兴趣区VOI(Vt),然后基于计算机自动膨胀算法将Vt外扩10 mm获得瘤体及瘤周VOI(Vt+Vp)。使用Pyradiomics软件分别从Vt和Vt+Vp中提取影像组学特征,随后采用15种特征选择方法和10种分类器构建150个预测模型,并通过十折交叉检验以验证模型的效能。使用准确度、敏感度、特异度、受试者工作特性曲线下面积(AUC)评估模型的效能,并比较性能最优的前三个预测模型。结果 MSCT四期增强扫描图像中预测HCC MVI状态的影像组学模型在门静脉期的表现优于其它期相及各期相的不同组合,其中最大的AUC值在Vt和Vt+Vp两种ROI中分别为0.768和0.782。此外,基于Vt+Vp的影像组学模型对MVI的预测效能优于基于Vt的影像组学模型,基于Vt+Vp性能最优的预测模型的AUC值、准确度、敏感度和特异度分别0.782、0.728、0.745和0.705。结论 采用影像组学方法术前无创性预测HCC MVI状态首选增强扫描的门静脉期,ROI首选瘤体联合瘤周10 mm区域。
Objective To investigate the value of single or different phases of contrast-enhanced multi-slice spiral CT(MSCT)in different volumetric regions of interest(ROI)to preoperatively predict the state of microvascular invasion in primary hepatocellular carcinoma(HCC)based on radiomics methods.Methods A total of 88 patients with HCC confirmed by surgical pathology who underwent preoperative MSCT quadruple-enhanced scan were retrospectively recruited,including 47 MVI-positive patients and 41 MVI-negative patients.The ROI was manually delineated slice-by-slice in the early arterial phase,late arterial phase,portal venous phase,and equilibrium phase of enhanced MSCT images to obtain the volume of tumor VOI(Vt),and then Vt was expanded by 10 mm through the computer expansion algorithm automatically to obtain the volume of tumor and peritumor(Vt+Vp).Pyradiomics software was used to extract radiomic features from Vt and Vt+Vp,followed by 150 discriminant models constructed with 150 feature selection methods and 10 classifiers,and then 10-fold cross-validation was used to evaluate the performance of these models.Using accuracy,sensitivity,specificity,area under the receiver operating characteristic curve(AUC)to assess model performance.The top three predictive models with the best performance were also compared.Results The radiomics model for predicting HCC MVI status in portal venous phase among quadruple-enhanced MSCT images outperformed other phases and different combinations of phases,achieving the highest AUC values of 0.768 and 0.782 in Vt and Vt+Vp respectively.In addition,the prediction performance of the radiomics model based on Vt+Vp was superior to models based on Vt.AUC value,accuracy,sensitivity,and specificity of the model with the best performance based on Vt+Vp were 0.782,0.728,0.745 and 0.705 respectively.Conclusions Radiomics models based on the portal venous phase of contrast-enhanced MSCT and tumor combined with the 10mm peritumoral area were more recommended to be employed to preoperative non-invasively predict the state of HCC MVI.
论著

Act1对高糖诱导肾小管上皮细胞炎症反应及细胞外基质表达的调控作用

Regulation effect of Act1 on high glucose induced inflammatory response and extracellular matrix expression in renal tubular epithelial cells

:21-27
 
目的 研究核因子-κB激活剂1(Act1)对高糖诱导肾小管上皮细胞炎症反应及细胞外基质表达的调控作用。方法 培养肾小管上皮细胞MK2,设置对照组和高糖组,处理12 h、24 h、48 h、72 h后检测细胞中Act1的mRNA和蛋白表达水平;设置si-NC组(5.5 mmol/L葡萄糖培养基中转染NC siRNA)、si-NC+高糖组(30 mmol/L葡萄糖培养基中转染NC siRNA)、si-Act1+高糖组(30 mmol/L葡萄糖培养基中转染Act1 siRNA),48 h后检测细胞中Act1、E-钙黏蛋白(E-cadherin)、N-钙黏蛋白(N-cadherin)、I型胶原(Col-I)、III型胶原(Col-III)的mRNA和蛋白表达水平以及培养基中肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、干扰素-γ(IFN-γ)的含量。结果 高糖组处理12 h、24 h、48 h、72 h时细胞中Act1的mRNA和蛋白表达水平均高于对照组(P<0.05);si-NC+高糖组处理48h时细胞中Act1、N-cadherin、Col-I、Col-III的mRNA和蛋白表达水平以及培养基中TNF-α、IL-1β、IFN-γ的含量均高于si-NC组,细胞中E-cadherin的mRNA和蛋白表达水平均低于si-NC组(P<0.05);si-Act1+高糖组处理48h时细胞中Act1、N-cadherin、Col-I、Col-III的mRNA和蛋白表达水平以及培养基中TNF-α、IL-1β、IFN-γ的含量均低于si-NC+高糖组,细胞中E-cadherin的mRNA和蛋白表达水平均高于si-NC+高糖组(P<0.05)。结论 Act1表达增加对高糖诱导肾小管上皮细胞炎症反应激活和细胞外基质增多具有促进作用。
Objective To study the regulation effect of nuclear factors-κB activator 1(NF-κB activator 1,Act1)on high glucose induced inflammatory response and extracellular matrix expression in renal tubular epithelial cells.Methods Renal tubular epithelial cells MK2 were cultured and control group and high glucose group were set.The mRNA and protein expression of Act1 were detected after treatment for 12,24,48 and 72 hours.MK2 were divided into si-NC group(transfected with NC siRNA in 5.5 mmol/L glucose medium),si-NC+high glucose group(transfected with NC siRNA in 30 mmol/L glucose medium)and si-Act1+high glucose group(transfected with Act1 siRNA in 30 mmol/L glucose medium).The mRNA and protein expression of Act1,E-cadherin,N-cadherin,type I collagen(Col-I),and type III collagen(Col-III)and the contents of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)in culture medium were detected.Results The mRNA and protein expression levels of Act1 in cells of high glucose group were higher than those of control group at 12 h,24 h,48 h and 72 h(P<0.05).The mRNA and protein expression levels of Act1,N-cadherin,CoL-I,Col-III in cells and the contents of TNF-α,IL-1β,IFN-γ in culture medium of si-NC+high glucose group were higher than those of si-NC group,the mRNA and protein expression levels of E-cadherin in cells were lower than those of si-NC group at 48 h(P<0.05).The mRNA and protein expression levels of Act1,N-cadherin,CoL-I,Col-III in cells and the contents of TNF-α,IL-1β,IFN-γ in culture medium of si-Act1+high glucose group were lower than those of si-NC+high glucose group,the mRNA and protein expression levels of E-cadherin in cells were higher than those of si-NC+high glucose group at 48 h(P<0.05).Conclusions The increased expression of Act1 promotes the activation of inflammatory response and the increase of extracellular matrix in renal tubular epithelial cells induced by high glucose.
综述

肝内胆管细胞癌诊治进展

Advances in diagnosis and treatment of intrahepatic cholangiocarcinoma

:100-105
 
肝内胆管细胞癌(ICC)是发病率仅次于肝细胞癌的肝脏恶性肿瘤,它的恶性程度高、术后易复发,且早期无典型症状,大多数患者在确诊时已处于晚期。诊断主要依赖于增强CT、MRI和实验室检查。肝切除术是ICC首选的治疗方法,完整的切缘阴性切除和保留足够残留肝是影响手术预后的重要因素。淋巴结清扫、卡培他滨辅助化疗已被证实对患者有益。局部治疗、分子靶向治疗、免疫治疗等新疗法发展迅速,为晚期ICC患者带来了希望。传统疗法与新疗法的结合为ICC提供新的诊疗思路。
Intrahepatic cholangiocarcinoma(ICC)is the second most common liver malignancy after hepatocellular carcinoma.It is highly malignant,easy to recur after surgery,and has no typical symptoms in the early stage,and most patients are in the late stage when diagnosed.Diagnosis relies on enhanced CT,MRI and laboratory tests.Hepatectomy is the preferred treatment for intrahepatic cholangiocarcinoma.Complete resection with negative margin and adequate residual liver preservation are important factors affecting the prognosis of the operation.Lymph node dissection and adjuvant chemotherapy with capecitabine have been shown to be beneficial for patients.The rapid development of new therapies such as local therapy,molecular targeted therapy and immunotherapy has brought hope to patients with advanced intrahepatic cholangiocarcinoma.The combination of traditional therapy and new therapy provide a new idea for diagnosis and treatment of intrahepatic cholangiocarcinoma.
论著

度普利尤单抗对瘙痒性皮肤病的效果及对嗜酸粒细胞恢复和生活质量的影响

Effect of Dupilumab on pruritic dermatosis,eosinophil recovery and quality of life

:74-77
 
目的 探讨度普利尤单抗对瘙痒性皮肤病的效果及对嗜酸粒细胞(EOS)恢复和生活质量的影响。方法 选取2021年2月—2022年1月期间,我院收治的瘙痒性皮肤病患者96例。根据治疗方式不同分为对照组(48例)和观察组(48例)。对照组给予传统激素治疗,观察组给予度普利尤单抗治疗。比较治疗前后2组血清炎症因子、免疫球蛋白水平情况;比较治疗前后2组症状积分下降指数(SSRI 评分)、神经激肽/速激肽受体1(NK1R)及EOS情况。观察2组疗效情况。采用皮肤病生活质量问卷(DLQI)对2组生活质量进行评价,并观察2组复发率情况。结果 治疗后,2组血清IFN-γ(干扰素-γ)、IL-2(白介素2)、IgA、IgG、IgM、NK1R、EOS水平升高,IL-4、IL-13、IgE水平及SSRI 评分降低,且观察组更明显(P<0.05)。观察组治疗有效率高于对照组(P<0.05)。随访6个月,观察组DLQI评分及复发率低于对照组(P<0.05)。结论 度普利尤单抗可减轻瘙痒性皮肤病患者瘙痒症状,增强机体防御力,促进嗜酸粒细胞恢复,提高其生活质量,值得临床推广应用。
Objective To investigate the effect of Dupilumab on pruritic dermatosis,eosinophil(EOS)recovery and quality of life.Methods From February 2021 to January 2022,96 patients with pruritic dermatosis were selected.According to different treatment methods,they were divided into control group(48 cases)and observation group(48 cases).The control group was treated with traditional hormone,and the observation group was treated with Dupilumab.The levels of serum inflammatory factors and immunoglobulin in the two groups were compared before and after treatment.The symptom score reduce index(SSRI score),neurokinin/tachykinin receptor 1(NK1R)and EOS were compared between the two groups before and after treatment.The curative effect of the two groups was observed.The quality of life of the two groups was evaluated with Dermatology Quality of Life Questionnaire(DLQI),and the recurrence rate of the two groups was observed.Results After treatment,levels of serum IFN-γ,IL-2,IgA,IgG,IgM,NK1R and EOS of two groups increased,while the levels of IL-4,IL-13,IgE and SSRI scores decreased,especially in the observation group(P<0.05).The effective rate of the observation group was higher than that of the control group(P<0.05).The DLQI score and recurrence rate in the observation group were lower than those in the control group(P<0.05)in 6 months follow-up.Conclusions Dupilumab can alleviate the itching symptoms of patients with pruritic dermatosis,enhance the body's defense,promote eosinophil recovery,and improve their quality of life,which is worthy of clinical application.
论著

11例慢性淋巴细胞白血病合并第二肿瘤的临床分析

Clinical analysis of 11 cases of chronic lymphocytic leukemia patients with second tumor

:23-27
 
目的 探讨慢性淋巴细胞白血病(CLL)合并第二肿瘤临床特征和预后。方法 回顾性分析2015年8月—2021年10月我院收治的58例CLL患者,其中有11例合并第二肿瘤,47例无合并第二肿瘤,分析两组病例的临床特征及其对预后的影响。结果 CLL合并第二肿瘤和无合并第二肿瘤患者在年龄、性别、白细胞计数、血红蛋白水平、淋巴细胞计数、血小板计数、乳酸脱氢酶(LDH)、β2-微球蛋白(β2-MG)水平、分期、单个基因缺失类型之间比较差异无统计学意义,但CLL合并第二肿瘤患者基因缺失个数较无合并第二肿瘤CLL患者组高(χ2=11.17,P=0.03),且总生存期较短。结论 CLL合并第二肿瘤患者常伴有多个基因缺失,且预后差,当CLL患者伴有多个基因缺失时,在诊治过程中需警惕有无合并第二肿瘤。
Objective To investigate the prognosis and clinical characteristics of chronic lymphocytic leukemia(CLL)patients with second tumor.Methods A retrospective analysis was performed on 58 cases of CLL patients who were diagnosed in our hospital from August 2015 to October 2021.The clinical data of 11 CLL patients with second cancer and 47 CLL patients without second cancer were compared and analyzed.Results There were no significant differences in age,sex,white blood cell count,lymphocyte count,platelet count,the level of serum β2-microglobulin and lactate dehydrogenase between two groups.However,in CLL patients with second cancer,the incidence of multiple genetic deletions was higher than those without second cancer(χ2 =11.17,P =0.03).The overall survival time was shorter in CLL patients with second primary cancer.Conclusions CLL patients with second tumor have a frequent multiple gene deletions and poor prognosis.Physicians should pay attention to second cancers when diagnosing the CLL patients with multiple gene deletions.
论著

TAK1与TCF-4在非小细胞肺癌中表达及其相关性的初步研究

Preliminary study on the expression and correlation of TAK1 and TCF-4 in non-small cell lung cancer

:17-22
 
目的 探讨非小细胞肺癌(NSCLC)组织中转化生长因子β激活激酶1(TAK-1)与T细胞因子-4(TCF-4)在 mRNA以及蛋白水平的表达情况及其相关性,并分析两者与NSCLC患者临床病理因素的关系。方法 收集NSCLC手术标本51例,每例均包含肺癌组织及配对癌旁组织,所有患者的术后诊断均经病理结果证实,通过RT-PCR以及Western blot法检测TAK1、TCF-4在癌组织及配对癌旁组织中的表达情况,并通过SPSS进一步分析两者的相关性及其与临床病理因素的关系。结果 TAK1与TCF-4 mRNA以及蛋白水平在NSCLC患者癌组织中均高表达,其中TAK1蛋白的表达与NSCLC的TNM分期(P=0.022)、淋巴结转移(P=0.014)相关,TCF-4蛋白的表达与NSCLC的TNM分期相关(P=0.045)。TAK1在NSCLC组织中的表达与TCF-4呈正相关(r=0.427,P=0.002)。结论 TAK1 mRNA及蛋白水平在NSCLC组织中均高表达,并与TCF-4呈正相关,TAK1有可能成为NSCLC诊断及预后的一个潜在靶标,并且TAK1与TCF-4的联合应用有可能成为一种更为理想的NSCLC辅助诊断及临床治疗方法。
Objective To investigate the mRNA and protein expressions of transforming growth factor β-activated kinase 1(TAK1)and T cell factor-4(TCF-4)in non-small cell lung cancer(NSCLC)tissues and their correlation,and to analyze the relationship between TAK1/TCF-4 and clinicopathological factors in NSCLC patients.Methods Cancer tissues and matched adjacent tissues of 51 NSCLC patients in our hospital were collected.The postoperative diagnosis of all patients was confirmed by pathological results.The expression of TAK1 and TCF-4 in cancer tissues and paired adjacent tissues were detected by RT-PCR and Western blot,then SPSS was used to further analyze the correlation between TAK1 and TCF-4 and clinicopathological factors.Results TAK1 and TCF-4 mRNA and protein were highly expressed in NSCLC tissues,and TAK1 protein expression was significantly correlated with TNM stage of NSCLC(P=0.022)and lymph node metastasis(P=0.014);TCF-4 protein expression was significantly correlated with TNM stage of NSCLC(P=0.045).TAK1 expression in NSCLC tissues was positively correlated with TCF-4(r=0.427,P=0.002).Conclusions TAK1 mRNA and protein were highly expressed in NSCLC tissues and positively correlated with TCF-4.TAK1 may become a potential target for the diagnosis and prognosis of NSCLC,and the combined application of TAK1 and TCF-4 may become a more ideal method for the auxiliary diagnosis and clinical treatment of NSCLC.
论著

不同孕期巨细胞病毒感染对母鼠行为的影响

Effects of CMV infection in different stages of maternal pregnancy on its behavior

:7-16
 
目的 研究母代不同孕期巨细胞病毒(CMV)感染对自身精神及行为的影响。方法 72只BALB/c雌鼠随机分为12组(A1、A2、A3、B1、B2、B3、C1、C2、C3、D1、D2、D3,每组6只),A为孕期再感染、B为既往感染、C为孕期原发感染、D为空白对照,1为孕早期、2为孕中期、3为孕晚期。母鼠腹腔注射小鼠CMV(murine CMV,MCMV)Smith株建立播散性感染模型,或注射无菌生理盐水建立对照模型。母鼠产仔后同笼合养,产后22 d分笼;母鼠做行为学试验。试验结束,每组随机处死3只母鼠;测量子宫、肝、脑脏器重量系数及唾液腺中MCMV含量。结果 A、B、C组母鼠产后次日体质量均低于D组(均P<0.05),其中C2、C3组母鼠低体质量情况持续至产后22日(均P<0.05)。A、B、C组母鼠唾液腺组织均测出MCMV。与D组母鼠相比,A1、C1组母鼠活胎率降低(均P<0.05),A、C组母鼠的子宫、肝、脑脏器系数升高(均P<0.05)且脑组织有病损表现。产后6天时,A3、B3、C组母鼠水平运动总距离和直立次数减少(均P<0.05),糖水偏好量降低(均P<0.05),悬尾不动时间延长(P<0.05);其中,C2、C3组母鼠以上行为退缩情况至产后22天仍存在,且有逃避潜伏时间延长(均P<0.01),穿越原平台位置次数减少(均P<0.01)情况。结论 孕期CMV感染损害母代身心健康,有可能增加子代不良抚养的风险。
Objective To investigate the effects of cytomegalovirus(CMV)infection in different stages of maternal pregnancy on its own spirit and behavior.Methods A total of 72 female BALB/c mice were randomly divided into 12 groups(each group had 6 mice):A1-A3,B1-B3,C1-C3,D1-D3(group A had re-infection,group B had previous infection,group C had primary infection,group D was blank control,group 1 was in early pregnancy,group 2 was in middle pregnancy,group 3 was in late pregnancy).The disseminative infection model was established by intraperitoneal inoculation of murine CMV(MCMV)Smith strain,and the blank control model was established by intraperitoneal inoculation of 0.9% sterile saline(NaCl).After 21 days of parturition,the mothers and offspring were reared in separate cages,mothers were selected for the behavior experiments.At the end of all the behavior tests,3 mothers in each group were killed randomly.Weighed and calculated the organ coefficients of the uteri,livers and brains,and detected the expression levels of MCMV in salivary gland.Results On the first day after delivery,the weights of mothers in groups A,B and C were lower than those in group D(all P<0.05),the low body weight of mice in C2 and C3 groups lasted to the 22th day(all P<0.05).The MCMV in salivary gland tissue were found in groups A,B and C,but not in group D.The live fetus rates of groups A1 and C1 were significantly lower than that of group D.The organ coefficients of uteri,livers and brains in groups A and C were higher than those in group D(all P<0.05).And the lesions of brain tissues in groups A and C were more serious than in the other groups.On the 6th day,compared with the other groups,the mothers of groups A3,B3 and C were significantly abnormal in the open field test,the tail suspension test and the sugar preference test(all P<0.05).But on 22th day,only the mothers of groups C2 and C3 were significantly abnormal in those tests(all P<0.01),and even in the water maze test(all P<0.01).Conclusions Maternal CMV infection in different stages pregnancy have impacts on mother mice's physical and mental health.Those bad situations may bring poor parenting to the offspring.
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