lNTRODUCTlON

Hepatic epithelioid hemangioendothelioma (EHE) is a rare malignant tumor of vascular origin, with an incidence of 0.1-0.2/100000[1,2]. Oral contraceptives, polyvinyl chloride, asbestos, thorotrast contrast medium, hepatic trauma, and viral hepatitis have been identified as risk factors for subsequent development of disease[3]. While laboratory findings always reveal abnormal liver function, tumor markers are always at normal levels. The patient described in this case report had a history of hepatitis A and normal liver function, but with a mildly elevated tumor marker [carcinoembryonic antigen (CEA)at 6.9 ng/mL]. The patient received four courses of chemotherapy and was found to remain in stable condition after 13 years of follow-up.

Consent was obtained from the patient, who signed a written informed consent for publication of this case report.

CASE PRESENTATlON

Chief complaints

A 46-year-old woman with no significant past medical history presented at the hospital with a 1-mo history of epigastric discomfort and asthenia.

History of present illness

The patient had no other symptoms.

History of past illness

The patient had a history of acute hepatitis that had resolved without complications 20 years previously.

Personal and family history

Research on the Transmission Mode of Offshore Wind Farm ZHENG Ming，WANG Changhong(99)

Physical examination

Physical examination revealed no remarkable findings.

耦合HEC-RAS模型和基于ArcGIS的HEC-GeoRAS模塊，對青海省玉樹縣巴塘河流域建立HEC-RAS模型，進行該區(qū)歷史洪水模擬，得到的主要結(jié)論如下：

Laboratory examinations

Laboratory testing on admission showed no abnormalities in markers of inflammation or abnormal liver function, or in peripheral blood panel or biochemical tests. Hepatitis B surface antigen (HBsAg),hepatitis B core antibody (HBcAb) and hepatitis C virus antibody (HCVAb) were negative. Tumor markers were in the normal ranges, except for a mildly elevated CEA (6.9 ng/mL; normal range: 0-5.0 ng/mL).

Laboratory testing on admission showed no abnormalities in markers of inflammation or abnormal liver function, or in peripheral blood panel or biochemical tests. HBsAg, HBcAb and HCVAb were negative.Tumor markers were in the normal ranges, except for a mildly elevated CEA (6.9 ng/mL; normal range:0-5.0 ng/mL).

綜上所述，人民幣匯率制度改革對我國宏觀經(jīng)濟影響頗大，涉及外匯儲備、物價、就業(yè)、貨幣供給、進出口、國際資本流動等方面，且其程度受人民幣匯率不同升貶值周期的影響。匯率制度改革的政策選擇和時機選擇也要受到宏觀經(jīng)濟因素的制約，兩者互相影響，具體影響及作用機制如圖1所示。

Imaging examinations

Abdominal ultrasound revealed multiple irregular hypoechoic lesions in the liver. Color doppler flow imaging showed spots of avascular reflective material. Contrast-enhanced computed tomography (CT)showed multiple low-density lesions in the right lobe of the liver. The largest was located in segment 8 and was 2.9 cm, 2.3 cm. Some lesions had mild-moderate enhancement during the arterial contrastenhanced phase. The density was lower than the normal liver parenchyma during the portal vein and lag phase (Figure 1). Magnetic resonance (MR) T1-weighted images showed multiple low signal ovoid lesions in the right lobe of the liver that had a high signal on T2-weighted images (Figure 2). Chest Xrays yielded no remarkable findings. Ultrasound revealed enlarged bilateral lymph nodes in the neck,axilla, and groin.

During the patient’s hospital stay, she was given four cycles of combined chemotherapy with ifosfamide, cisplatin, epirubicin and recombinant human (rh) endostatin (Endostar; Simcere, Nanjing,China) injection.

LABORATORY EXAMlNATlONS

生成式模型將采用聯(lián)合概率score(x,y|θ)（其中，已知序列為x，依存分析結(jié)構(gòu)為y，模型的參數(shù)為θ）生成一系列依存句法樹，并賦予其概率分值，然后采用相關(guān)搜索算法找到概率打分最高的分析結(jié)果作為最后輸出。在句法分析中，已知序列輸入的是句子；輸出的是依存結(jié)構(gòu)樹T。生成式模型的最終目標是從訓(xùn)練模型中獲取使聯(lián)合概率P(T,S)取得最大值的參數(shù)θ，得分最高的依存結(jié)構(gòu)樹。為了便于計算聯(lián)合概率P(T,S)，可以對句法分析問題作出不同程度的假設(shè)，這將有效減少數(shù)據(jù)稀疏問題。

FlNAL DlAGNOSlS

An ultrasound-guided fine needle aspiration biopsy revealed few hepatocytes and fibrous tissue with mildly heteromorphic spindle cell (dendritic cell) infiltration. The neoplastic cells were medium to large,with eosinophilic cytoplasm and vesicular nuclei having small, inconspicuous nucleoli. Signet ring celllike structures were seen with intracytoplasmic lumina, occasionally containing red blood cells(Figure 3). Immunohistochemical staining indicated that the tumor cells were positive for CD31(H12164PD590, EuroBioscience), CD34 (H12166F, EuroBioscience), and factor VIII-related antigen(FVIII-RAG, BH0012044, Goybio) (Figure 4A-C), while cells were negative for Pan Cytokeratin(CK+AFs-AE1/AE3+AF0-) (PD00330, Dako) (Figure 4D). Other results were lysozyme+-, P53+-/+ACYndash+ADs-, vimentin+-, EMA+-, CK8+ACY-ndash+ADs-, AFP+ACY-ndash+ADs-, CK18+ACYndash+ADs-, hepatocyte+ACY-minus+ADs-, CK20+ACY-minus+ADs-, and CD68+ACY-minus+ADs-,which weren't been shown in this article. Immunohistochemical staining results revealed evidence of+ACY-nbsp+ADs- endothelial differentiation, and consistent with hepatic epithelioid hemangioendothelioma (EHE).

The patient had no personal or family history of other diseases.

TREATMENT

如何有效讓學(xué)生自身的生活經(jīng)驗得到積累呢，教師可以為學(xué)生開展口頭作文的訓(xùn)練。從客觀的角度來講，說話與作文是分不開的，大膽的說話練習(xí)在有助于學(xué)生寫作的同時，可以促進學(xué)生對生活經(jīng)驗的總結(jié)。教師可以在課前五分鐘，針對學(xué)生展開聽說的聯(lián)系，教師可以拋出一個話題，如“使你最為興奮的事情是什么”？讓學(xué)生以口頭的形式完成一篇簡短的作文。通過這簡短的幾分鐘，可以有效的讓學(xué)生針對生活經(jīng)驗進行一次總結(jié)，為其之后的作文語言打下基礎(chǔ)。

OUTCOME AND FOLLOW-UP

After 13 years of follow-up, the patient remains in stable condition. A repeated CT scan found that the size of the lesions had not changed (Figure 5) and her liver function was normal.

DlSCUSSlON

Hepatic EHE is a rare tumor of vascular origin, with an incidence of 0.1-0.2/100000[1,2]. Fewer than 600 cases involving the liver are available in the literature, and it was first reported by Ishak[4] in 1984.Hepatic EHE is as a low-to-moderate grade tumor with a malignant potential intermediate between hemangioma and hemangiosarcoma[4]. Its metastasis rate is 27%-45% and the most common tissues of origin are the lungs (81%) and celiac lymph nodes (39%)[1]. The median age has been reported as 41.7 years, with a female predominance of 3:2[3], and the clinical manifestations are variable. The most frequent symptoms are right upper quadrant pain (48.6%), hepatomegaly (20.4%), and a constitutional syndrome with progressive liver damage and weight loss (15.6%)[3]. Some patients present with Budd-Chiari syndrome or liver failure, while others present with incidental findings[1,5]. Laboratory findings may reveal abnormal liver function. Nearly 75% of patients have elevated alkaline phosphatase (AKP),2.7% have elevated alpha-fetoprotein (AFP), and 18.8% have elevated serum CEA[1,3]. Our patient had good liver function, with normal AKP, AST, ALT, and AFP. Her CEA was elevated but other markers were in their normal ranges. Oral contraceptives, polyvinyl chloride, asbestos, thorotrast contrast agent,and hepatic trauma have been identified as risk factors for subsequent disease development[3], and viral hepatitis is considered as an etiology[1,4,6]. This patient had a history of viral hepatitis A, but it had resolved without complication 20 years before she presented with hepatic EHE, making a viral etiology implausible. Because of its nonspecific manifestation, the diagnosis of hepatic EHE depends mainly on radiology and histopathology.

Most lesions are peripheral, extending to the capsular margin and are frequently hypoechoic with heterogeneous internal architecture on sonography[7,8]. On CT, lesions are almost hypodense with peripheral contrast enhancement[7,9-11]. Capsular retraction adjacent to the mass is seen in fewer than 25% of patients[9,12]. On MR, T1-weighted images of lesions frequently have a low signal and T2-weighted images have heterogeneous-increased signals. Peripheral enhancement with a thin nonenhancing rim corresponding to a narrow vascular zone can be seen with arterial contrast[7,11-13].A lollipop sign, which is indicative of hepatic or portal veins terminating at or just within the periphery of lesions, seems to be specific for hepatic EHE[14]. The mean apparent diffusion coefficients of lesions were found to be high compared with other hepatic malignancies, which may be helpful in suggesting the diagnosis[15]. MR appears to be superior to CT, and MR with contrast may be important.

Pathologic diagnosis depends on the vascular nature of the tumor. Histologically, it is comprised of a fibrous stroma with myxohyaline areas including dendritic and epithelioid cells, often with intracellular vacuoles[1,4]. Immunohistochemical staining is positive for the expression of endothelial antigens, such as FVIII-RAG (98%), CD34 (94%), or CD31 (86%), and negative for epithelial markers[1,6]. This tumor was CD34+, vimentin+, and CD31+, and negative for epithelial markers like CK (AE1/AE3) and CK18.Podoplanin was shown to be specifically expressed in hepatic EHE (78%), and may be useful as a diagnostic marker of EHE in liver tumors[9]. Characteristic ultrastructural features include investing basal lamina, cytoplasmic intermediate filaments, Weibel-Palade bodies, and pinocytotic vesicles[4].High cellularity, more than mitotic count, predicts an unfavorable prognosis[1,3,4]. A recent study reported that these tumors often have t(1;3) (p36.3; q25) translocations, resulting in WWTR1-CAMTA1 fusion[16]. YAP 1-TFE3 fusions have also been identified in about 10% of patients[17].

Treatment options are limited by the rarity of the tumor and currently include liver transplantation(44.8%), chemotherapy or radiotherapy (21.0%), and liver resection (9.4%), with 24.8% of patients receiving no treatment[3]. Complete liver resection should be performed if possible, but the multicentric origin of the tumor and multinodular growth make that difficult to accomplish[18]. Liver transplantation is an effective treatment for patients who are not candidates for resective surgery and those with extrahepatic manifestations or progressive liver failure[19,20]. Hepatic EHE is not sensitive to radiotherapy or chemotherapy, but some studies have found that 5-fluorouracil, doxorubicin,thalidomide, and interferon were effective[14,21,22]. One-year survivals following liver transplantation,without treatment, radiotherapy or chemotherapy, and liver resection have been reported as 96%,39.3%, 73.3%, and 100%. The corresponding 5-year rates were 54.5%, 4.5%, 30%, and 75%[3]. Hepatic EHE is of vascular origin, vascular endothelial growth (VEGF) receptors have been detected in EHE tumor cells, and VEGF has a role in tumor growth[23]. Combination treatment anti-VEGF drugs and cell cycle inhibitors, such as bevacizumab and capecitabine[24,25], pegylated liposomal doxorubicin[26],and metronomic cyclophosphaide[27] have been effective. For patients with extrahepatic lesions, it has been reported that adjuvant chemotherapy may prevent recurrence[28].

Because the disease was multifocal in our patient, orthotopic liver transplantation may have been justified as a curative procedure. Unfortunately, a donor shortage and cost limitations made immediate transplantation unrealistic. Consequently, we choose to treat her with combined chemotherapy that included ifosfamide, cisplatin, epirubicin and rh-endostatin. rh-endostatin is purified in ansystem, with an additional nine amino acid sequence of soluble protein[29]. It targets neovascular endothelial cells and has antiangiogenetic and antitumor activity. Preclinical and clinical studies showed synergistic effects of rh-endostatin and other agents that inhibit the growth of malignant tumors, with minimal toxicity[30-32]. A review by Xu[33] suggests that the combination of rhendostatin with chemotherapy, radiotherapy, and biotherapy (fusion protein, or molecular-targeted therapy on cancers,) may be the optimal strategy for cancer treatment[33]. Ling[34] reported that the antiangiogenic activity of rh-endostatin was mediatedandby blocking VEGFinduced tyrosine phosphorylation of KDR/Flk-1 in endothelial cells. The vascular nature and endothelial origin of our patient’s tumor led us to choose rh-endostatin for her treatment. To date, the size of her lesions has not increased, and the patient is in stable condition with normal liver function.The patient is followed-up regularly, and liver transplantation is still recommended.

CONCLUSlON

In conclusion, hepatic EHE is a rare tumor, and its atypical symptoms and varied radiographic appearance make it hard to differentiate from other tumors. Diagnosis depends on histopathology.Liver resection is the treatment of choice in patients with resectable lesions, and liver transplantation is justified as a curative procedure for multinodular disease. Donor shortage and a long waiting time,among other reasons, limit the use of liver transplantation. Chemotherapy including rh-endostatin may increase the effectiveness of hepatic EHE treatment. The focus is on its therapeutic efficacy while awaiting a suitable donor liver and for patients with extrahepatic manifestations. Further research is needed.

FOOTNOTES

Zhejiang Medical and Health Science and Technology Project, No. 2021429795; and Scientific Research Project of Zhejiang Education Department, No. Y202043306.

Mo WF collected the data and wrote the manuscript; Tong YL designed the report; all authors have read and approve the final manuscript.

她哼著歌站在路上打的，坐上車她依然哼著歌，絲毫沒有發(fā)現(xiàn)司機驚詫的眼神，她望向窗外，發(fā)現(xiàn)車子好久都沒啟動時問：“師傅，怎么不開車??！”

The authors declare that they have no competing interests.

The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

準確稱取（0.2 ± 0.01）g樣品（城市固體廢棄物模擬組分和廚余沼渣）與0.2 g艾士卡混合劑在坩堝中（研磨至粒度小于0.2 mm）均勻混合。再用1 g艾士卡混合劑將其全覆蓋，在馬弗爐中 680℃下灼燒3 h，待燃燒完畢后將灼燒樣品從馬弗爐中取出。在通風(fēng)櫥冷卻至室溫后，加入適量去離子水，將灼燒樣品轉(zhuǎn)移至250 mL燒杯中，隨后將燒杯中的懸濁液在2 μm孔徑的水相定性濾紙上進行抽濾，并用去離子水反復(fù)沖洗坩堝和燒杯內(nèi)壁3次，將沖洗液全轉(zhuǎn)移至抽濾器中。最后用去離子水反復(fù)沖洗抽濾器和濾紙中的殘渣，將濾瓶中所得的濾液轉(zhuǎn)移至250 mL的容量瓶中并定容。

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China

Wei-Fang Mo 0000-0003-4286-3229; Yu-Ling Tong 0000-0002-3772-9327.

Xing YX

A

Xing YX