系统治疗是原发性肝癌及肝转移癌的重要手段之一，尤其是对不可手术切除的肝肿瘤。早期评估肿瘤的治疗反应对于调整诊疗方案十分重要，并有助于预测预后。超声造影是肝脏病变诊断及监测的重要手段，能实时显示肿块的大小、数量及血流灌注状态。笔者对近年来超声造影、术中超声造影、三维超声造影等技术在肝脏恶性肿瘤系统治疗效果评估中的应用现状及研究进展进行总结和分析。

Background: Long non-coding RNA (lncRNA) was identified as a novel diagnostic biomarker in gastric cancer (GC). However, the functions of lncRNAs in immuno-microenvironments have not been comprehensively explored. In this study, we explored a critical lncRNA, LOC339059, that can predict the clinical prognosis in GC related to the modulation of PD-L1 and determined its influence upon macrophage polarization via the IL-6/STAT3 pathway. Methods: To date, accumulating evidence has demonstrated that the dysregulation of LOC339059 plays an important role in the pathological processes of GC. It acts as a tumor suppressor, regulating GC cell proliferation, migration, invasion, tumorigenesis, and metastasis. A flow cytometry assay showed that the loss of LOC339059 enhanced PDL1 expression and M2 macrophage polarization. RNA sequencing, RNA pull-down, RNA immunoprecipitation, Chip-PCR, and a luciferase reporter assay revealed the pivotal role of signaling alternation between LOC339059 and c-Myc. Results: A lower level of LOC339059 RNA was found in primary GC tissues compared to adjacent tissues, and such a lower level is associated with a poorer survival period (2.5 years) after surgery in patient cohorts. Moreover, we determined important immunological molecular biomarkers. We found that LOC339059 expression was correlated with PD-L1, CTLA4, CD206, and CD204, but not with TIM3, FOXP3, CD3, C33, CD64, or CD80, in a total of 146 GC RNA samples. The gain of LOC339059 in SGC7901 and AGS inhibited biological characteristics of malignancy, such as proliferation, migration, invasion, tumorigenesis, and metastasis. Furthermore, our data gathered following the co-culture of THP-1 and U937 with genomic GC cells indicate that LOC339059 led to a reduction in the macrophage cell ratio, in terms of CD68+/CD206+, to 1/6, whereas the selective knockdown of LOC339059 promoted the abovementioned malignant cell phenotypes, suggesting that it has a tumor-suppressing role in GC. RNA-Seq analyses showed that the gain of LOC339059 repressed the expression of the interleukin family, especially IL-6/STAT3 signaling. The rescue of IL-6 in LOC339059-overexpressing cells reverted the inhibitory effects of the gain of LOC339059 on malignant cell phenotypes. Our experiments verified that the interaction between LOC339059 and c-Myc resulted in less c-Myc binding to the IL-6 promoter, leading to the inactivation of IL-6 transcription. Conclusions: Our results establish that LOC339059 acts as a tumor suppressor in GC by competitively inhibiting c-Myc, resulting in diminished IL-6/STAT3-signaling-mediated PDL1 expression and macrophage M2 polarization.

ObjectiveThe objective of the study was to explore the CT and ultrasound features and clinical significance of perivascular epithelioid cell tumor (PEComa) of the liver.MethodsEleven hepatic PEComa patients treated in our hospital were retrospectively analyzed based on the characteristics of the imaging results of the patients, including conventional ultrasound, CDFI, contrast-enhanced ultrasound (CEUS), and contrast-enhanced CT (CECT).ResultsCT scans showed that all lesions were hypodense. Ultrasonography showed that lesions were either hyperechoic (4/11, 36.36%), hypoechoic (4/11, 36.36%), isoechoic (1/11, 9.09%), or heterogeneously echoic (2/11, 18.18%). CDFI showed that most of the lesions had an abundant blood supply (9/11, 81.82%). Whether on CT scan or ultrasonography, the margins of the lesions were dominated by clear margins. Ultrasonography revealed more features: hyperechoic patterns around lesions (3/11, 27.27%) and lateral shadow (5/11, 45.45%). The CDFI showed that large blood vessels were observed around the lesions (9/11, 81.82%). CECT shows two enhancement patterns: “fast in and fast out (FIFO)” (8/11, 72.72%) and “fast in and slow out (FISO)” (3/11, 27.27%). CEUS shows that all lesions had the enhancement pattern of “FISO,” which was different from CECT. All lesions displayed rapid enhancement during HAP in CEUS during 7–20 s. Four patients (36.36%) washed out at 60–180 s, another four (36.36%) washed out at 180–300 s, and the remaining three patients (27.27%) showed no signs of washout even at 360 s.ConclusionSome imaging features, such as clear margins, peripheral hyperechoic around the lesion, lateral shadow, the large blood vessels around lesions, and the “FISO” enhancement pattern, may indicate expansive growth of the tumor and be helpful in the diagnosis of PEComa. Ultrasound images may provide more details for clinical reference.

目前,肺部疾病的诊断临床中主要依靠X线、CT和气管镜,但由于X线、CT具有放射性,不宜反复应用,气管镜虽然具有较高的安全性,但会引起患者疼痛等不适,且可能引起纵隔感染等并发症,因此上述方法的应用均存在局限性.近年来,超声检查在肺部疾病的应用日渐广泛,逐渐引起临床的重视,且随着新一代超声造影剂声诺维的出现及普及,超声造影(contrast enhanced ultrasound,CEUS)目前已广泛应用于多种组织和器官,其可实时动态观察组织和病变内血流及微血管灌注情况,诊断率与增强CT和MRI相当[1-3].故本文主要针对肺部疾病的CEUS诊断研究进行总结,重点阐述CEUS检查在肺周疾病中的诊断价值及对穿刺活检的指导价值.

目的 分析慢性肝炎、肝硬化合并肝外恶性肿瘤病史患者超声(US)、超声造影(CEUS)及两者联合诊断原发性肝细胞癌(HCC)的价值,并与穿刺活检病理对照分析.方法 研究对象为406例有慢性肝炎、肝硬化病史的肝肿瘤患者,其中,50例既往有肝外恶性肿瘤病史,356例无肝外恶性肿瘤病史.所有患者均在获得病理诊断前进行US和CEUS检查并进行诊断,诊断结果与穿刺活检病理对照.结果 50例肝肿瘤US、CEUS及两者联合诊断HCC结准确度分别为68％、78％及82％,三者之间无明显统计学差异(P＞0.05).50例肝肿瘤与356例肝肿瘤进行比较,US、CEUS及两者联合诊断HCC灵敏度、阳性预测值及准确度均有明显统计学差异(P＜0.05),CEUS诊断HCC的阴性预测值有明显统计学差异(P＜0.05).结论 慢性肝炎、肝硬化合并肝外恶性肿瘤病史患者肝肿瘤US、CEUS及两者联合诊断HCC有一定的局限性,治疗前穿刺活检对鉴别肝肿瘤性质有重要临床意义.

近年来,随着医学技术的成熟,影像组学得到快速的发展和广泛的应用,超声影像组学作为影像组学的一个分支,逐渐应用到肝癌、乳腺癌等领域,一些研究成果得到了临床医生的认可.在肝脏病变的研究中,超声诊断是一种重要的影像诊断方法,但存在一定的局限性,对良恶性的诊断特异性不如增强电子计算机断层扫描或磁共振成像.随着超声影像组学的引入及进展,为提高肝脏病变良恶性鉴别能力,肿瘤分期分级以及疾病的预后研究提供了新的方法和思路.

近年来,以射频消融(radio frequency ablation, RFA)为代表的肝癌局部治疗,由于微创及安全有效,已被临床医师认可,成为肝细胞癌(hepatocellular carcinoma,HCC)的根治性治疗选择之一.但是,受到仪器条件的限制,RFA对于较大肝肿瘤和位置不佳的肝肿瘤,治疗相对困难,复发及并发症风险增加.随着RFA治疗手段及治疗观念的成熟,RFA联合肝动脉化疗栓塞术(transcatheter arterial chemoembolization,TACE)、无水乙醇注射(percutaneous ethanol injection,PEI)以及化疗等技术可以提高较大肝癌的治疗效果.对于特殊位置的肝癌,应用个体化RFA技术及辅助方法也可取得较好的治疗结果.本文回顾性分析了近年来国内外关于RFA治疗肝癌的基础及临床研究,尤其是总结了较大肝癌和特殊位置肝癌的治疗技术、策略及疗效.

患者女,54岁.主因“腰酸胀痛1年余,不伴血尿”入院.外院CT提示右肾占位,双肾多囊肾改变.有家族性多囊肾病史,未规律影像检查.查体双肾区无叩击痛.入院尿常规检查提示:尿潜血(1+),尿蛋白(+),尿白细胞(1+);血生化未见明显异常.泌尿系统超声提示:双肾失常态,皮髓质结构不清晰,双肾可见弥漫多发互不相通无回声结节.右肾下极可见类类圆形低回声实性占位,约7.8 cm×7.0cm×6.0cm,边界清,形态规则,彩色多普勒显示占位内可见较丰富血流信号(图1).超声检查结果:多囊肾、右肾癌可能.右肾下极占位行手术切除,病理结果提示:肾透明细胞癌伴坏死.

目的 比较采用平行双针法与单纯双针法两种布针模式行超声引导下射频消融术治疗肝癌的局部疗效.方法 回顾性分析2014年1月至2018年12月于北京大学肿瘤医院行射频消融治疗的肝癌患者临床资料.根据射频消融布针模式分为平行双针组、 单纯双针组.射频消融治疗后1个月,行增强CT或MRI检查测量消融范围(长径、宽径及厚径)并计算肿瘤灭活率.对患者随访,观察肿瘤局部进展情况.结果 共281例(370个病灶)符合纳入及排除标准的患者入选本研究,经倾向评分匹配法校正后最终纳入分析111例(111个病灶),其中平行双针组37例(37个病灶),单纯双针组74例(74个病灶).平行双针组消融厚径大于单纯双针组(均值差=0.39,95％CI:-0.63～-0.15,P=0.002),两组消融长径、 宽径差异均无统计学意义(均值差=0.07,95％CI:-0.33～0.20,P=0.631;均值差=-0.03,95％CI:-0.20～0.24,P=0.844).两组治疗后1个月肿瘤灭活率均为100％;中位随访时间6个月,平行双针组肿瘤局部进展率低于单纯双针组(2.70％比16.22％,P=0.037).结论 两种布针模式射频消融均具有较好的肿瘤灭活率,平行双针法可能更易形成较大的消融范围,以完全覆盖肿瘤组织,从而降低肿瘤局部进展率.

目的 临床探讨平行法及交叉法两种布针模式在肝脏肿瘤RFA的效果差异,寻找最佳布针方案.方法 采用Celon射频治疗仪及200T30电极针2根,应用离体牛肝进行RFA实验.布针方式分为两种,平行法布针即两组消融区的布针点连线呈"="型,交叉法布针即两组消融区的布针点连线呈"x"型.设置布针点的最短距离(2 cm,2.5 cm,3 cm)及输出功率(20 W,25 W,30 W)分别消融并比较.消融结束后1h取材,测量并记录大体病理标本消融凝固区形态、范围、长径、短径及交界处凹陷深度.镜下观察不同组消融区交界处病理组织学改变.结果 应用25 W功率,布针点距离为2 cm、2.5 cm及3 cm时,两种模式布针的凝固范围均随着布针点距离增加而增大,而交界处凹陷深度亦随着距离的增加而增大,距离3 cm时,融合不佳.当针尖距离固定时,两种模式的长径相似,未见明显差异,而平行法的短径显著长于交叉法的短径[2 cm:(4.64±0.21)cm比(3.84±0.38)cm,P=0.003;2.5 cm:(5.15±0.25)cm比(4.20±0.40)cm,P=0.011;3 cm:(5.96±0.39)cm比(5.12±0.52)cm,P=0.020].当功率固定时,平行法与交叉法的长径相似,差异未见统计学意义,而平行法短径显著长于交叉法短径[20 W:(4.70±0.26)cm比(4.13±0.15)cm,P=0.033;25 W:(5.15±0.25)cm比(4.20±0.40)cm,P=0.011;30 W:(5.27±0.40)cm比(4.50±0.26)cm,P=0.027].当针距为2.5 cm和3 cm时,平行法的交界处凹陷深度明显短于交叉法[2.5 cm:(1.04±0.23)cm比(1.94±0.32)cm,P=0.007;3 cm:(2.09±0.18)cm比(3.53±0.64)cm,P=0.001].不同功率下,平行法的交界处凹陷深度同样短于交叉法[20 W:(1.61±0.56)cm比(3.60±0.53)cm,P=0.011;25 W:(1.04±0.23)cm比(1.94±0.32)cm,P=0.007;30 W:(0.90±0.44)cm比(1.83±0.15)cm,P=0.010].结论 两种布针模式的凝固范围均随着针距和功率的增加而增大,平行法的短径均长于交叉法,交界处凹陷距离均短于交叉法,提示平行布针法优于交叉布针法,在射频过程中更能融合形成有效的消融范围以达到完全覆盖肿瘤组织的目的 ,为肝肿瘤射频消融临床布针方案的设计提供了依据.

目的 观察超声造影到达时间参数成像鉴别诊断胆囊病变的价值.方法 回顾分析25例胆囊癌和22例胆囊良性病变胆囊患者的超声检查资料,根据到达时间参数成像评估灌注动脉模式,评价到达时间参数,包括病灶到达时间、同深度肝组织到达时间、病灶与同深度肝组织的到达时间差(△T).结果 胆囊良恶性病变间灌注动脉模式差异有统计学意义(P＜0.001).恶性病变动脉模式多呈分支型和不规则型,良性病变多呈散在点状型和单支型,而病灶到达时间差异无统计学意义(P＞0.05).良恶性病变之间△T[造影剂到达胆囊与到达同深度肝组织的时间差,分别为(-0.21±1.37)s和(-2.69±1.37)s]差异有统计学意义(P＜0.001).取△T截断值为-1.05 s,其诊断敏感度、特异度、阳性预测值、阴性预测值和准确率分别为81.80％、92.00％、85.20％、90.00％和87.20％.结论 超声造影到达时间参数成像有助于鉴别诊断胆囊良恶性病变.

目的 探讨肝癌射频消融(RFA)治疗后三维超声造影(3D-CEUS)表现及其诊断价值.方法 分析我院行RFA治疗且治疗后24 h内行3D-CEUS检查的肝癌患者92例共99个病灶,将其分为残留复发组及完全灭活组,分析两组病灶3D-CEUS表现.结果 将3D-CEUS表现分为结节增强型、片状增强型、环状增强型、无增强型.残留复发组与完全灭活组间在结节增强型及环状增强型的差异具有统计学意义(P=0.000、0.026).结论 4种3D-CEUS分型表现对肝癌RFA后残留或复发灶的诊断具有较大应用价值.

ObjectiveTo retrospectively analyze contrast‐enhanced ultrasound ( CEUS ) manifestations of neuroendocrine tumors ( NET s ) liver metastases ,and explore the relationship between CEUS parameters and differentiation of NETs . Methods From January 2014 to June 2018 ,36 patients who had been performed CEUS due to liver metastasis of NET s with pathological diagnosis and immunohistochemical staining results were enrolled in this study . T he CEUS findings of NET s liver metastases were summarized . According to the Ki‐67 index ,CgA results ,and the stage G ,the patients were divided into Ki‐67＞20% group and Ki‐67≤20% group ,CgA negative group and CgA positive group ,and group G1+G2 and group G3 ,respectively . T he CEUS parameters of NET s liver metastases between the above groups were compared . Results In 36 lesions ,during the arterial phase of CEUS ,66 .7% ( 24/36 ) showed hyperenhancement , 16 .7% ( 6/36 ) isoenhancement , 13 .9% ( 5/36 ) rim‐like enhancement , and 5 .6% ( 2/36 ) hypoenhancement ; During the portal phase , 13 .9% ( 5/36 ) showed hyper or iso enhancement ,86 .1% ( 31/36) showed hypoenhancement . T he average washout time was ( 67 .5 ± 56 .1) s ,of w hich 5 ( 13 .9% ) lesions were washed out after 120 s . T he mean starting washout time was statistically different between the CgA negative group and the positive group [ ( 91 .6 ± 81 .5) s vs ( 60 .1 ± 38 .7) s , P ＝0 .001] . T here was no statistically significant difference in all observations between the group of Ki‐67≤20% and ＞20% ,group G1+G2 and group G3 ( P ＞0 .05) . Conclusions CEUS of NET s liver metastasis has certain characteristics ,among which hyperenhancement is its main enhancement mode ,and some lesions have a longer wash out time . T he relationship with the degree of differentiation needs further investigation .

目的 探讨经皮超声引导下射频消融(RFA)治疗结直肠癌肝转移(CRLM)外科切除术后肝内复发癌的临床疗效.方法 回顾性分析外科切除术后肝内复发并接受经皮RFA治疗的CRLM患者46例(68个病灶),平均年龄为(58.8±10.8)岁(39～81岁).肝脏切除术中切除肝转移病灶平均数目为(3.7±2.8)个(1～12个).肝切除术后发现肝内新生病灶的时间为(6.3±7.0)个月(1～35个月).结果 RFA治疗后肿瘤灭活率为97.1％ (66/68),肿瘤局部复发率为5.9％ (4/68),肝内新生转移发生率为78.3％ (36/46).患者1、3、5年总体生存率为91.3％、41.5％、28.3％,6个月、1年肝内无进展生存率分别为50.0％、34.8％.单因素分析结果显示,手术切除病灶数＞3灶(P=0.044)、CEA水平(P=0.035)和肿瘤最大径＞3 cm (P=0.017)是影响患者生存率的潜在危险因素.多因素Cox模型回归分析结果显示,肿瘤最大径＞3 cm(P=0.24,HR=2.476,95％CI:1.129～5.429)是患者生存率的独立影响因素.严重并发症的发生率为2.2％ (1/46).结论 RFA治疗CRLM外科切除术后肝内复发是安全和有效的.肝脏肿瘤最大径≤3 cm的患者接受RFA治疗预后较好.

An oxidative cascade cyclization of β-keto esters has been developed for the construction of the tricyclic picrotoxane motif in a single step, and DFT calculations suggested a possible cationic cyclization mechanism. This cascade cyclization can be operated on a 20 g scale to obtain a 77% total yield of the tricyclic products, which in turn can be converted to versatile intermediates for further elaboration to picrotoxanes and their structurally related compounds.

A concise formal synthesis of (+)-phomactin A has been achieved. The key features of this synthetic strategy involve a one-pot Prins/Conia-ene cyclization protocol for the construction of the highly functionalized 1-oxadeclin core (AB ring) and a late-stage direct γ-hydroxylation of enone for the installation of the C ring.

Objective To compare the visualization ability for thyroid nodular among superb micro-vascular imaging (SMI), power Doppler flow imaging (PDFI), and color Doppler flow imaging(CDFI), and determine optimal vascular findings for the diagnosis of thyroid nodules. Methods A total of 58 thyroid nodules from 50 patients were enrolled, including 27 benign nodules (benign group) and 31 malignant nodules (malignant group). Vascular patterns of these nodules were detected by SMI, PDFI and CDFI, respectively. Results Thyroid cancer was characterized by type III vascular pattern. Only central vascularity performed best in detecting thyroid cancers. When using the criterion, SMI performed a better specificity (96.3%) and sensitivity (77.4%) than PDFI (92.5%, 41.9%) and CDFI (88.9%, 48.3%); and the specificity of SMI was significantly higher than the others (all P<0.01). Conclusions The sign of only central is of value in distinguishing malignant thyroid nodules. SMI is better on presenting thyroid nodular than CDFI and PDFI, and it could be used to differentiate thyroid nodules. Key words: Ultrasonography; Thyroid nodule; Superb microvascular imaging; Vascularity; Vascular pattern

Objective To investigate the incidence and risk factors of liver abscess after radiofrequency ablation (RFA) for liver cancer.Methods A retrospective study was performed on 1 643 patients from January 2000 to June 2016.All the patients were diagnosed with hepatocellular carcinoma (HCC,n =942),cholangiocellular carcinoma (CCC,n =31) or metastatic liver carcinoma (MLC,n=670).Univariate and multiple Logistic regression analysis were used to evaluate the risk factors of liver abscess.Results The incidence of liver abscess after RFA was 0.79％％ (13/1 643).Univariate analysis indicated that the liver abscess was significantly correlated with the history of diabetic mellitus (DM),Child-Pugh level,history of surgery and tumor location (all P＜0.05).Multivariate analysis showed that the history of DM,history of surgery and tumor location were independent risk factors of liver abscess after RFA for liver cancer.Conclusion History of DM,surgery and tumor location are important factors that result in liver abscess after RFA.

Objective To investigate the efficacy and prognostic factors of percutaneous ultrasound-guided radiofrequency ablation (RFA) for liver metastases from gastric cancer.Methods Clinical and imaging data of 55 patients with liver metastasis from gastric cancer who underwent percutenous ultrasound-guided RFA were retrospectively analyzed,and the overall survival rates and prognostic factors were assessed.Results The overall survival rates of 1-,2-,3-and 5-year was 70.45％,42.90％,20.32％ and 10.16％,respectively.The ablation rate was 94.12％ (96/102) 1 month after RFA,and the local recurrent rate was 15.69％ (16/102),the new metastasis rate was 52.73％ (29/55).Age (P=0.015),tumor number (P=0.011),extrahepatic metastasis before RFA (P=0.026) and chemotherapy after RFA (P=0.031) were significantly prognostic factors.Age (P=0.033),tumor number (P=0.004) as well as chemotherapy after RFA (P=0.001) were independent prognostic factors.The severe complication rate was 1.82％ (1/55),while no treatment-related death occurred.Conclusion Percutaneous ultrasound-guided RFA is a safe and effective therapeutic option for liver metastases from gastric cancer.Age,tumor number,chemotherapy after RFA are independent prognostic factors.

MiR‐130a‐3p was found to play tumor suppressor role in most human cancers, except for gastric cancer. However, in this study, we demonstrated that miR‐130a‐3p was significantly down‐regulated in gastric carcinoma (GC) tissues compared with adjacent non‐neoplastic tissues, and decreased miR‐130a‐3p expression was associated with shorter overall survival (OS) and was an independent prognostic factor for OS in GC patients. Over‐expression of miR‐130a‐3p remarkably inhibited not only GC cell migration, invasion, and epithelial‐mesenchymal transition (EMT) in vitro, but also tumorigenesis and lung metastasis in the chick embryo chorioallantoic membrane (CAM) assay in vivo. Conversely, inhibition of miR‐130a‐3p resulted in opposite phenotype changes in GC cells. Furthermore, TBL1XR1 was identified as a direct target of miR‐130a‐3p, and reintroduction of TBL1XR1 into miR‐130a‐3p‐transfected MGC‐803 cells reversed the inhibitory effects of miR‐130a‐3p on GC cell migration, invasion and EMT. Taken together, our data suggested that miR‐130a‐3p suppressed aggressive phenotype of GC cells partially by direct targeting and decreasing TBL1XR1 and subsequent EMT process.