Elevated serum α-fetoprotein level of nude mice bearing hepatoma cells by treatment with monoclonal antibodies to α-fetoprotein

This study was carried out to clarify the reason for elevation of serum α-fetoprotein (AFP) level of nude mice bearing hepatoma cells after treatment with monoclonal antibodies (MoAbs) to AFP. MoAbs to AFP showed no effect on the cumulative amounts of AFP secreted from human hepatoma cell line, HuH-7, in vitro. However, the treatment of nude mice bearing HuH-7N cells (HuH-7 xenograft) with MoAbs to AFP led to elevation of the serum AFP level in spite of the fact that the growth curve of HuH-7N cells was similar to that for PBS treatment. This apparent elevation of the serum AFP level is thought to be due to the slow elimination of AFP-MoAb immune complexes with little lattice structure from circulation, but not the enhancement of AFP secretion of HuH-7N cells. Thus, when using a MoAb alone or MoAb-drug conjugate, the serum AFP level should only be cautiously used as a tumor marker for evaluating the targeting immunotherapy.     

The synergistic effects of interleukin 2 and interleukin 7 on the proliferation and autologous tumor cell lysis of tumor-associated lymphocytes

Interleukin-7 (IL-7) has an ability to stimulate the proliferation of pre-B cells. It has been shown that IL-7 can also activate T lymphocytes. We here demonstrate that IL-7 in combination with interleukin-2 (IL-2) can drive cell proliferation and enhance the autologous tumor cell lysis by peripheral blood mononuclear cells (PBMC) and autologous mixed lymphocyte tumor cell culture (MLTC)-derived effector cells (MLTC cells). These synergistic effects of IL-2 and IL-7 on the proliferation and the augmentation of autologous tumor cell lysis were found for both effector cells. These effects were inhibited by neutralizing antibodies to IL-2 or IL-7, and by a combination of both antibodies, significantly. In terms of phenotypical expression, CD3 positive cells comprised the vast majority of MLTC cells after culture in medium containing IL-2 and IL-7 with an increase of IL-2 receptor positive cells.Abbreviations CD cluster differentiation - IFN interferon - IL interleukin - JRU Japanese Reference Unit - LAK lymphokine activated killer - mAb monoclonal antibody - MLTC mixed lymphocyte tumor cell culture - PBMC peripheral blood mononuclear cells - TILs tumor infiltrating lymphocytes     

嵌合抗原受体T细胞治疗的现状与展望

肿瘤严重威胁着人类健康,当前肿瘤传统的治疗方法有手术治疗、化疗、放疗和靶向药物治疗等。近年来,肿瘤免疫治疗,尤其是嵌合抗原受体（chimeric antigen receptor,CAR） T细胞免疫疗法在基础研究与临床应用中蓬勃发展,并在治疗血液系统恶性肿瘤方面取得了巨大成功。然而,大量研究显示,细胞免疫治疗后可出现不同程度的毒副反应,且部分患者缓解后再次复发。因此,了解细胞治疗面临的挑战与局限性,寻找解决的办法,对继续发挥细胞免疫疗法的潜能具有重要意义。本文就免疫细胞的CAR结构、病毒载体的选择、细胞治疗面临的挑战及前景进行综述。     

人胎肝细胞分泌的低分子抑瘤物对白血病细胞的抑制作用

本工作证明了在胎儿组织中存在一类低分子天然肿瘤抑制物,它是胎儿组织细胞生成和分泌的,对瘤株细胞和原代白血病细胞有选择性抑制作用。初发期或复发期急性非淋巴细胞白血病患者的骨髓在体外液体培养条件下与肝细胞上清及其甲醇提取物共同孵育4d,可使所有病例的骨髓AML—CFU降低到不可检出的程度。因而,低分子天然抑瘤物是天然肿瘤免疫中的一个组成部分,它在肿瘤的诊断和治疗中有着深远的意义。     

Quantitative Detection of 15 Serum Bile Acid Metabolic Products by LC/MS/MS in the Diagnosis of Primary Biliary Cholangitis

To determine 15 bile acid metabolic products in human serum by liquid chromatography-tandem mass spectrometry (LC/MS/MS) and value their diagnostic outcome in primary biliary cholangitis (PBC). Serum from 20 healthy controls and 26 patients with PBC were collected and went LC/MS/MS analysis of 15 bile acid metabolic products. The test results were analyzed by bile acid metabolomics, and the potential biomarkers were screened and their diagnostic performance was judged by statistical methods such as principal component and partial least squares discriminant analysis and area under curve (AUC). 8 differential metabolites can be screened out: Deoxycholic acid (DCA), Glycine deoxycholic acid (GDCA), Lithocholic acid (LCA), Glycine ursodeoxycholic acid (GUDCA), Taurolithocholic acid (TLCA), Tauroursodeoxycholic acid (TUDCA), Taurodeoxycholic acid (TDCA), Glycine chenodeoxycholic acid (GCDCA). The performance of the biomarkers was evaluated by the AUC, specificity and sensitivity. In conclusion, DCA, GDCA, LCA, GUDCA, TLCA, TUDCA, TDCA and GCDCA were identified as eight potential biomarkers to distinguish between healthy people and PBC patients by multivariate statistical analysis, which provided reliable experimental basis for clinical practice.     

腮腺肿瘤患者行游离保留SMAS术后的复发及预后影响因素分析

摘要 目的：探讨腮腺肿瘤患者行游离保留SMAS术后的复发及预后影响因素分析。方法：以我院2016年3月-2022年1月收治的60例腮腺肿瘤患者作为研究对象。所有患者均行游离保留SMAS联合全腮腺切除术治疗。术后进行随访。采用χ²检验和独立样本t检验进行腮腺肿瘤患者预后复发及预后存活情况的亚组分析。采用Pearson检验进行相关性分析;采用Cox回归模型计算腮腺肿瘤患者预后的独立危险因素。结果：复发和未复发患者性别、年龄、BMI、糖尿病病史和高血压病史无显著差异（P＞0.05）;复发和未复发患者的淋巴结转移、病理类型、TNM分期、AJCC临床分期差异显著（P<0.05）;预后死亡和预后存活患者性别、年龄、BMI、糖尿病病史和高血压病史无显著差异（P＞0.05）;预后死亡和预后存活患者的淋巴结转移、病理类型、TNM分期、AJCC临床分期和复发情况差异显著（P<0.05）;淋巴结转移、病理类型、TNM分期、复发、AJCC临床分期与腮腺肿瘤患者预后存活情况密切相关（P<0.05）;多因素Cox分析结果显示,淋巴结转移、病理类型、TNM分期、复发、AJCC临床分期是独立危险因素（P<0.05）。结论：疾病相关因素是导致腮腺恶性肿瘤患者复发和死亡的重要因素,临床早期可针对性调整治疗方案以降低患者术后复发和恶性肿瘤。     

肝硬化原发性肝癌直径<1 cm超声造影表现及其与血清AFU、AFP-L3、GPC3、TSGF、GP73水平相关性研究

摘要 目的：探讨肝硬化原发性肝癌（PHC）直径<1cm超声造影（CEUS）表现及其与血清α-L-岩藻糖苷酶（AFU）、甲胎蛋白异质体-L3（AFP-L3）、磷脂酰肌醇蛋白聚糖-3（GPC3）、肿瘤特异生长因子（TSGF）、高尔基体糖蛋白（GP73）水平相关性。方法：选取2018年1月-2022年8月于湖北省襄阳市中医院收治的肝硬化PHC直径<1 cm患者44例,根据术后病理结果分为高分化组、中分化组和低分化组。所有患者术前均完善CEUS和血清AFU、AFP-L3、GPC3、TSGF、GP73水平检查。比较三组CEUS表现、定量时间-强度曲线（TIC）分析、血清AFU、AFP-L3、GPC3、TSGF、GP73水平。采用Spearman相关性分析肝硬化PHC直径<1 cm患者的CEUS表现与血清AFU、AFP-L3、GPC3、TSGF、GP73水平的相关性。结果：44例肝硬化PHC直径<1 cm患者的CEUS表现均为肝内单发病灶,呈圆形或类圆形,病灶边界清晰,周围可见声晕。不同分化程度肝硬化PHC直径<1 cm患者在动脉期、门脉期和延迟期的CEUS表现上差异均无统计学意义（P＞0.05）。高分化组、中分化组和低分化组的达峰时间、廓清时间和峰值加速时间逐渐减少,差异有统计学意义（P＜0.05）。而高分化组、中分化组和低分化组的峰值强度增加率逐渐增加,差异有统计学意义（P＜0.05）。高分化组、中分化组和低分化组的增强时间对比差异无统计学意义（P＞0.05）。高分化组、中分化组和低分化组血清AFU、AFP-L3、GPC3、TSGF、GP73水平逐渐升高,差异有统计学意义（P＜0.05）。Spearman相关性分析显示,达峰时间、廓清时间和峰值加速时间与血清AFU、AFP-L3、GPC3、TSGF、GP73水平呈负相关（P＜0.05）;峰值强度增加率与血清AFU、AFP-L3、GPC3、TSGF、GP73水平呈正相关（P＜0.05）。结论：肝硬化PHC直径<1 cm患者的CEUS表现均为肝内单发病灶,呈圆形或类圆形,病灶边界清晰,周围可见声晕。CEUS表现和血清AFU、AFP-L3、GPC3、TSGF、GP73水平具有相关性,两者可辅助鉴别肝硬化PHC直径<1 cm的不同分化程度。     

血清肿瘤标志物与宫颈癌病理特征的关系及对术后复发的预测研究

摘要 目的：探讨血清肿瘤标志物与宫颈癌病理特征的关系及对术后复发的预测研究。方法：选择2015年1月至2017年12月来我院诊治的宫颈癌患者82例作为观察组,选择同期来我院体检的健康女性者50例,两组均使用电化学发光免疫分析法检测血清中的CA125、CA153、CA199、CEA水平,观察组患者随访时间截至2022年12月。对比两组血清CA125、CA153、CA199、CEA水平,分析观察组患者血清CA125、CA153、CA199、CEA水平与临床病理特征的关系,分析观察组患者术后随访复发情况,宫颈癌根治术后患者复发的单因素与多因素Cox回归结果,血清CA125、CA153、CA199、CEA水平对宫颈癌根治术后复发的预测价值。结果：观察组的血清CA125、CA153、CA199、CEA水平明显较对照组高（P<0.05）。宫颈癌患者不同FIGO分期、间质浸润深度及是否存在淋巴结转移间血清CA125、CA153、CA199、CEA水平对比有统计学意义（P<0.05）。82例患者随访时间为13~60个月,中位生存时间为39个月,截止2022年12月末次随访,82例患者术后复发18例（21.95%）。单因素及多因素Cox回归分析表明,FIGO分期在ⅡA期、间质浸润深度≥1/2、有淋巴结转移、CA125≥307.41 U/mL、CA153≥185.89 U/mL、CA199≥153.23 U/mL、CEA≥30.15 ng/mL是影响宫颈癌术后复发的独立危险因素。ROC曲线显示,CA125+CA153+CA199+CEA预测宫颈癌术后复发的AUC明显较CA125、CA153、CA199、CEA单独指标预测价值高（P<0.05）。结论：宫颈癌患者血清CA125、CA153、CA199、CEA高表达,其与间质浸润深度、FIGO 分期、淋巴结转移、术后复发有关,四者联合可作为宫颈癌术后复发的预测指标。     

超声造影定量分析联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效的预测价值

摘要 目的：探讨超声造影定量分析联合血清甲胎蛋白（AFP）、血管内皮生长因子受体-2（VEGFR-2）、可溶性T细胞免疫球蛋白粘蛋白分子3（sTim-3）对原发性肝癌肝动脉化疗栓塞（TACE）治疗疗效的预测价值。方法：选择2020年1月至2022年10月海军军医大学第二附属医院收治的原发性肝癌患者94例。行TACE治疗2个月,采用改良的实体瘤疗效评价标准评估患者疗效,根据不同疗效分为疗效不良组（n=32）和疗效良好组（n=62）。所有患者均行超声造影检查,比较两组超声造影定量分析参数、治疗前血清AFP、VEGFR-2、sTim-3水平,采用受试者工作特征（ROC）曲线分析超声造影定量分析参数联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效的预测价值。结果：经TACE治疗,62例患者疗效良好、32例患者疗效不良,治疗有效率为65.96%。疗效良好组术前超声造影达峰时间、等增强开始时间显著长于疗效不良组（P<0.05）。疗效良好组术前血清AFP、VEGFR-2、sTim-3水平显著低于疗效不良组（P<0.05）。ROC曲线分析结果显示,超声造影定量分析联合血清AFP、VEGFR-2、sTim-3对原发性肝癌TACE治疗疗效预测的曲线下面积（AUC）为0.950,灵敏度为84.85%,特异度为82.12%,高于各指标单独检测。结论：超声造影定量分析参数、血清AFP、VEGFR-2、sTim-3水平可预测原发性肝癌患者TACE治疗的疗效,且联合诊断的预测效能更高。     

一套新的籼稻初级三体的选育和细胞学鉴定

以秋水仙素处理中籼３０３７幼苗,从其后代中获得同源三倍体１株。为选育成套初级三体,将中籼３０３７同源三倍体茎节幼芽置于试管中离体繁殖,繁殖后的同源三倍体种于田间,授以正常中籼３０３７的花粉。获得３０１３粒种子,成苗１０６３株。通过染色体数目检查,共获得３０２株三体植株。这些三体按其形态特征可分为１２类,对每类三体植株分别通过粗线期的染色体鉴定,获得了１２种初级三体,依据额外染色体长度递减的顺序分别定名为三体１、三体２、………三体１２。