支气管哮喘患者外周血Th17 与Th9 细胞的变化及临床意义

目的:探讨Th17、Th9 细胞水平在支气管哮喘患者中的表达及其临床意义。方法:选取67 例哮喘患者为研究对象,30 例健康体检者为对照组,根据全球哮喘防治倡议(GINA)将哮喘患者分为间歇与轻度持续组20 例,中度持续组25 例和重度持续组22 例。收集患者临床资料,完成哮喘控制测试(ACT)评分、肺功能和呼出气一氧化氮(FeNO)值测定,流式细胞仪检测外周血PBMC 中CD3+ CD8- IL-17+ 、CD3+ CD8- IL-9+细胞水平。结果:与健康对照组相比,哮喘患者Th17、Th9 细胞水平均明显升高(P<0.05);中重度哮喘患者Th17 及Th9 细胞水平显著高于间歇与轻度哮喘组(P<0.05),而间歇与轻度哮喘组患者与健康对照组比较,差异无统计学意义(P>0.05)。哮喘患者外周血Th17 及Th9 细胞的表达均与FeNO 值正相关(r 值依次为0.501、0.438;P<0.05),与ACT 评分、肺功能FEV1、FEV1/ FVC 及PEF 负相关(r 值依次为-0.441、-0.362;-0.307、-0.377;-0.419、-0.411;-0.428、-0.24;P<0.05),同时Th17 与Th9 细胞在哮喘患者外周血中的表达率正相关(r 值为0.443,P<0.05)。结论:Th17、Th9 细胞在哮喘患者中高表达,具有协同致炎作用,且与症状严重程度相关,提示Th17 及Th9 细胞对哮喘患者病情评估有潜在的参考价值。     

miR-145-5p靶向TPM3通过ERK信号通路抑制甲状腺癌TPC-1细胞侵袭和转移

目的 探讨miR-145-5p对甲状腺癌细胞侵袭和转移的影响.方法 将miR-145-5p mimic质粒、mimic-NC质粒、TPM3质粒分别或联合转入甲状腺癌细胞,RT-qPCR检测miR-145-5p与TPM3 mRNA的表达,双荧光素酶报告检测靶向关系,Transwell法检测细胞侵袭能力,划痕实验检测细胞迁...     

中医斜扳疗法治疗腰椎间盘突出的生物力学研究

目的对椎间盘突出等腰椎病中医推拿斜扳疗法进行生物力学建模分析研究,比对脉冲激励的传统斜扳法和简谐激励的改良斜扳法两种不同手法的力学特性。方法假设椎骨为刚体,椎间盘及周围韧带等软组织为黏弹性体,建立模拟L1～5的5自由度振动系统,对基本方程进行解析求解。结果简谐激励改良斜扳法的疗效与频率有关。在频率≤1的简谐激励改良斜扳法作用下,病变节段最大位移都大于脉冲激励传统斜扳法下的最大位移。随着病变位置下移,简谐激励改良斜扳法的损伤比相比脉冲激励传统斜扳法逐渐下降,安全性增高。结论使用频率≤1的简谐激励改良斜扳法,治疗效果优于脉冲激励传统斜扳法,且可控制损伤。     

HIF-1α及其相关信号转导通路在疾病中的研究进展

缺氧诱导因子1α(HIF-1α)是在缺氧或炎症环境中被诱导的转录因子。与HIF-1β结合成异源二聚体后能够入核识别并结合缺氧反应原件(HRE,5′-RCGTG-3′),从而启动相关基因如炎症因子IL-1β、糖酵解相关酶LDHA、PKM等基因进行转录,其在细胞增殖、代谢及凋亡中发挥重要作用并参与多种转导通路在不同疾病的发生发展中产生影响。本文对HIF-1α的结构、功能及其在肿瘤及炎症中参与的调控通路及研究进展进行概述。     

SH2D1A基因突变的淋巴瘤患儿6例病例系列报告

背景：SH2D1A 基因突变的儿童淋巴瘤临床罕见且有其特殊的临床特征及疾病预后。 目的：总结伴SH2D1A基因突变的儿童淋巴瘤临床表现、病理特点、治疗方案和预后。 设计：病例系列报告。 方法：纳入2017年6月至 2022年7月于首都医科大学附属儿童医院（我院）初诊为淋巴瘤且年龄＜18岁,经高通量全外显子基因测序提示SH2D1A 基因突变的连续住院病例。根据病理诊断确定治疗方案：侵袭性成熟B细胞淋巴瘤基于改良的LMB89方案治疗;成熟T细胞淋巴瘤合并家族性噬血细胞综合征（HLH）患儿先以HLH方案控制病情,确诊后予SMILE方案化疗。化疗2~3个月行中期疗效评估。化疗结束后3个月评估超声和PET/CT,化疗结束第1、2年内每3个月评估瘤灶超声、肝功能、LDH和免疫功能。 主要结局指标：SH2D1A基因突变淋巴瘤患儿的临床特征和预后。 结果6例伴SH2D1A基因突变淋巴瘤患儿,均为男性;中位发病年龄5（4~12）岁。瘤灶累及胃肠道3例,中枢神经系统、头颈部和多脏器浸润各1例;临床分期：Ⅱ期1例,Ⅲ期3例,Ⅳ期2例;病理类型：3例弥漫大B细胞淋巴瘤,1例高级别成熟B细胞淋巴瘤,1例伴11q异常的伯基特样淋巴瘤,1例儿童系统性EB病毒阳性T细胞淋巴瘤。5例患儿体液免疫和/或细胞免疫指标下降。5例病初全血和血浆EBV DNA均阴性,其中2例病程中复测全血EBV DNA上升至≥105拷贝数/mL;1例病初合并HLH,多次全血EBV DNA为106拷贝数/mL。6例均提示SH2D1A基因突变,2例完善SAP蛋白检测未见异常;1例染色体异常。3例完成化疗,2例因HLH死亡,1例予利妥昔单抗免疫治疗。 结论：SH2D1A基因突变的淋巴瘤患儿临床少见,病理形态多表现为非霍奇金淋巴瘤（成熟B细胞淋巴瘤）,预后较差,在合适时机考虑行异基因造血干细胞移植可改善疾病预后。     

新型MR对比剂长循环超顺磁氧化铁脂质体纳米微粒的体内外实验研究

目的 评价自制新型MR对比剂:长循环超顺磁性氧化铁(superparamagnetic iron oxide,SPIO)脂质体纳米微粒的药代动力学.方法 以加入SPIO为对照组,加入长循环SPIO脂质体纳米微粒为实验组.(1)巨噬细胞的体外吞噬实验:将巨噬细胞株RAW 264.7经复苏、培养,细胞达到80%～90%融合后,以每孔2.5×105个细胞接种于培养板,对照组和实验组细胞与不同浓度药物孵化后,分别测定细胞中Fe浓度和Fe染色情况,并用析因设计的方差分析对结果进行统计学处理.(2)小鼠体内药物分布实验:C57BL/6J雄性小鼠6只,每组2只,设为空白对照组、对照组、实验组,经尾静脉分别注射生理盐水、SPIO以及长循环SPIO脂质体后牺牲动物,经病理检查观察2组药物在体内的分布情况.(3)荷肺癌裸鼠MR成像实验:建立20只BALB/c裸鼠移植型肺癌模型,分为对照组和实验组,每组10只,分别经尾静脉注入SPIO和长循环SPIO脂质体纳米微粒后行MR扫描,测量增强前后2组实验动物各时间点肝脏和肿瘤ROI的信号强度,绘制信噪比(SNR)时间动态变化曲线,采用协方差分析比较2组动物肝脏及肿瘤增强12 h 后SNR差异有无统计学意义.(4)细胞毒性实验(噻唑蓝,MTT法):检查2种药物对人肝细胞株HL-7702细胞的毒性作用,用析因设计的方差分析对结果进行统计学处理.结果 (1)巨噬细胞的体外实验:析因分析结果表明,对照组细胞内Fe含量明显高于实验组,差异有统计学意义(F=296 839.9,P=0.000).普鲁士蓝染色显示对照组巨噬细胞染色较深,实验组巨噬细胞染色较浅.(2)小鼠体内药物分布实验:对照组肝、脾、肺、肾组织内蓝染颗粒多于实验组.(3)荷肺癌裸鼠MR成像实验:平扫对照组肝脏SNR为31.47±0.56,实验组为30.89±1.41;增强扫描12 h后对照组为17.00±0.96,实验组为22.29±0.73.平扫对照组肿瘤SNR为58.41±0.61,实验组为58.44±1.08;增强扫描12 h后对照组为58.50±0.63,实验组为52.47±1.18.经协方差分析表明增强12 h后对照组肝脏SNR显著低于实验组(F=167.022,P=0.000);而实验组肿瘤 SNR显著低于对照组(F=266.106,P=0.000).(4)细胞毒性实验:随着培养液中Fe浓度的增加,HL-7702细胞生存率均有下降趋势,但析因分析结果表明,实验组药物的细胞毒性较对照组低(F=2256.204,P=0.000).结论 长循环SPIO脂质体纳米微粒在体内外均有较好的抗巨噬系统吞噬功能,在体内实现了长循环,对非网状内皮系统的肿瘤也具有良好的T2负性被动靶向强化效果;同时还降低了SPIO对细胞的毒性作用.

Abstract：

Objective To evaluate pharmacodynamics of prepared long-circulating superparamagnetic iron oxide (SPIO) liposomes. Methods Control and experimental groups were established after adding SPIO or long-circulating SPIO liposomes as agents. (1)Macrophages experiment in vitro: the RAW 264.7 macrophage cell strains were recovered, cultured and seeded in the culture plate at a density of 2.5×105 cells/well until they reached 80%-90% confluence. The intracellular Fe uptake of control and experimental group cells were quantified by Ferrozine assay after incubation with different concentrations of drugs. Factorial design analysis of variance was used as statistics method. Prussian blue staining method was used to detect staining of experimental cells.(2)Drug biodistribution in mice: C57BL/6J(n=6) were classified into blank control group (n=2), control group(n=2) and experimental group(n=2).Saline, SPIO and long circulating SPIO were injected via the tail vein in the blank control group, control group and experimental group respectively. Then distribution of drugs in the body was observed by pathological examination.(3) MR imaging of tumor-bearing nude mice: 20 BALB/c nude mice bearing lung cancer models were established and classified into control group and experimental group. After administration of drugs, all animals underwent MR scanning. Signal intensities of livers and tumors were measured, SNR-time dynamic curves were drew. Covariance analysis was used to compare post-enhanced SNR at the 12th hour. (4)Cytotoxicity studies (MTT): cytotoxicity of both drugs on human liver cell line HL-7702 was studied, and statistically analyzed using factorial design analysis of variance. Results (1) Macrophages experiment in vitro: The nanoparticle uptake by macrophage cells evaluated by ferrozine assay showed the uptake of blank SPIO was higher than long-circulating SPIO liposomes. Compared with the blank control group, there was strong blue staining in the macrophages with Prussian staining in the control group and little blue staining in the experimental group. (2) Drug biodistribution in mice: for blue stained cells composed of iron particles, the amounts in the liver, spleen, lung, kidney of the control group were more than those in the experimental group. (3) MR imaging of tumor-bearing nude mice: the non-enhanced SNR of livers and tumors in the control group and experimental group were 31.47 ± 0.56, 30.89 ± 1.41, 58.41 ± 0.61, 58.44 ± 1.08, respectively. After injecting of contrast agents, SNR of livers and tumors in the control group and experimental group were 17.00 ± 0.96, 22.29 ± 0.73, 58.50 ± 0.63, 52.47 ± 1.18, respectively. The covariance analysis showed that SNR of the livers in the control group after 12 hours was significantly lower than the experimental group (F=167.022, P=0.000); while the SNR of the tumors in the experimental group was significantly lower than the control group (F=266.106, P=0.000).(4) Cytotoxicity of nanoparticles by MTT method: the viability of HL-7702 cells tend to decrease with the increase of Fe concentration. Cytotoxicity in the long-circulating SPIO liposomes was lower than the SPIO(F=2256.204,P=0.000). Conclusions Long-circulating SPIO liposomes we prepared reveal suitable sizes, even distribution, and good anti-macrophage ability in vitro and in vivo. They have long circulation characteristic and T2 negative enhancement effect in the transplanted lung cancers, while they still maintain low cytotoxicity.     

原发性肺黏膜相关淋巴组织淋巴瘤的18F-FDG PET/CT影像学表现

目的 分析原发性肺黏膜相关淋巴组织（MALT）淋巴瘤的18F-FDG PET/CT影像学表现,提高对原发性肺MALT淋巴瘤的认识及诊断能力。 方法 回顾性分析2006年11月至2017年4月经病理确诊的9例原发性肺MALT淋巴瘤患者（男性6例、女性3例,中位年龄59岁）的临床资料及18F-FDG PET/CT显像资料,记录病灶的部位、数量、密度、大小、形态及最大标准化摄取值（SUV_max）,以及纵隔及肺门淋巴结等情况;分析影像信息并同时进行相关文献复习。 结果 9例原发性肺MALT淋巴瘤患者18F-FDG PET/CT表现分为3型:实变型4例、肿块型3例、弥漫肺炎型2例。实变型表现为大小、受累范围不等的实变影;肿块型表现为单发或多发、边缘毛糙的实性肿块影;弥漫肺炎型表现为肺叶内或双肺弥漫的斑片、团块样软组织密度影。在9例患者中可见支气管充气征8例（部分伴有支气管扩张）、三角型灌注征3例、病灶向中心聚拢4例、钙化2例、胸腔积液2例、肺门及纵隔淋巴结肿大2例。所有病灶18F-FDG 代谢不均匀增高,中位SUV_max为6.0（2.6~8.3）;2例弥漫肺炎型纵隔及肺门淋巴结18F-FDG摄取异常增高,SUV_max分别为13.0、4.7。 结论 原发性肺MALT淋巴瘤的18F-FDG PET/CT表现常为斑片状致密影,多见实变影,内部常见支气管充气征,18F-FDG轻度摄取,结合相对缓慢的病程,可考虑为原发性肺MALT淋巴瘤。     

光动力疗法联合适形调强放疗治疗肿瘤的临床研究

目的 探讨局部光动力疗法(photodynamic therapy,PDT)联合区域适形调强放疗(intensity modulated comformed radiotherapy,IMCRT)治疗的剂量效应,为中晚期肿瘤患者提供不同策略的有效综合治疗依据.方法 对手术失败或无手术适应证的空腔或浅表肿瘤患者,采用局部区域的综合治疗手段,观察PDT治疗在不同时间、能量密度、分次(TDF)与IMCRT/中医药治疗的量效关系.即分析在一定能量密度下照射20 min/次、30 min/次或照射1次、3次,以及不同能量密度即200 J/cm2、300 J/cm2下PDT治疗与疗效之间的关系.结果 PDT联合IMCRT和中医药治疗肿瘤,随着TDF的变化有显著统计意义,PDT对中晚期肿瘤特别是空腔脏器患者,减轻症状提高生活质量是肯定的,对梗阻型、放化疗失败的中晚期肿瘤患者有较高的姑息治疗价值.结论 采用PDT、IMCRT与中药不同策略的综合治疗,通过TDF的优化方案,创伤性小、不良反应少,可达到减毒增效带瘤生存的目的,使中晚期肿瘤患者"变不治为可治".     

疏血通对急性缺血性脑卒中的临床疗效研究

目的 评价疏血通在急性缺血性脑卒中的临床疗效.方法 选择急性缺血性脑卒中患者196例,按随机数字表法分为治疗组(98例)和对照组(98例),分别在入院时及治疗后2周进行神经功能缺损评分、认知功能障碍评估及临床结局评定,并用经颅多普勒监测治疗前后脑血流量变化.结果 治疗组神经功能及临床结局改善及明显改善率明显高于对照组,而恶化病例明显减少.2组治疗后认知功能障碍评分均较治疗前明显改善,差异有统计学意义(P＜0.05),其中治疗组改善更显著.治疗后2组脑血流量较治疗前明显增加,差异有统计学意义(P＜0.05),其中治疗组改善更显著.结论 疏血通治疗急性缺血性脑卒中疗效显著,值得推广应用.

Abstract：

Objective To evaluate the therapeutic effect of Shuxuetong injection on acute ischemic stroke. Methods One hundred and ninety-six patients with acute ischemic stroke were randomly divided into Shuxuetong injection treatment group (n=98) and control group (n=98). The neurological deficiency scores, scores of cognitive dysfunction and clinical outcomes were evaluated; and the cerebral blood flow were evaluated by Doppler before treatment and 2 weeks after the therapy.Results The improvement of neurological function and clinical outcomes in the Shuxuetong injection treatment group was more obvious as compared with that in the control group and the improvement rate of patients in the treatment group was higher than that in the controls; Patients in the Shuxuetong injection treatment group enjoyed less worsening than the controls. The cognitive dysfunction 2 weeks after the therapy were significantly improved as compared with those before treatment (P＜0.05); and the cerebral blood flow after the treatment was significantly increased as compared with that before the treatment (P＜0.05); these improvements in the Shuxuetong injection treatment group were much obvious as compared with those in the controls. Conclusion Shuxuetong is effective in treating cerebral ischemic patients.