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Malignant pinealoma observed in the deep cerebral parenchyma of a male Wistar rat 雄性Wistar大鼠脑深部实质中恶性松果体瘤的观察
IF 1.2 4区 医学 Q4 PATHOLOGY Pub Date : 2021-11-25 DOI: 10.1293/tox.2021-0047
Mizuho Takagi, Y. Yamaguchi, S. Yamakawa, K. Tamura
This report describes a case of spontaneous malignant pinealoma in a 90-week-old male Wistar rat. The tumor mass occurred in the deep cerebral parenchyma and no intact pineal gland was observed in the area between the posterior-dorsal median line of the cerebrum and the cerebellum. The tumor was characterized by a large nodular proliferation occupying the central area of the brain, extending from the dorsal surface to the base of the brain, corresponding to the thalamus. The tumor cells had round to irregular oblong nuclei approximately 5–17 μm in diameter and showed faintly or moderately eosinophilic cytoplasm and indistinct cell boundaries. Immunohistochemically, the tumor cells were positive for synaptophysin and partially positive for neuron-specific enolase (NSE). The tumor showed malignant features including cellular pleomorphism, high mitotic index, necrotic foci, and invasive and extensive growth and was, therefore, diagnosed as an extremely rare malignant pinealoma in the deep cerebral parenchyma.
本报告描述一例自发性恶性松果体瘤在一个90周龄雄性Wistar大鼠。肿瘤肿块发生于脑深部实质,大脑后背中线至小脑间未见完整的松果体。肿瘤的特征是一个巨大的结节增生,占据了大脑的中心区域,从背表面延伸到大脑底部,与丘脑相对应。肿瘤细胞细胞核直径约5 ~ 17 μm,呈圆形或不规则的长圆形,胞浆呈轻度或中度嗜酸性,细胞边界不清。免疫组化结果显示,肿瘤细胞突触素阳性,神经元特异性烯醇化酶部分阳性。肿瘤表现为细胞多形性、高有丝分裂指数、坏死灶、侵袭性和广泛性生长等恶性特征,因此诊断为一种极其罕见的恶性脑深部实质松果体瘤。
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引用次数: 0
Luteal toxicity evaluation in rats 大鼠黄体毒性评价
IF 1.2 4区 医学 Q4 PATHOLOGY Pub Date : 2021-11-18 DOI: 10.1293/tox.2021-0058
Yoshikazu Taketa
The corpora lutea (CL) are endocrine glands that form in the ovary after ovulation and secrete the steroid hormone, progesterone (P4). P4 plays a critical role in estrous and menstrual cycles, implantation, and pregnancy. The incomplete rodent estrous cycle stably lasts 4–5 days and its morphological features can be distinguished during each estrous cycle stage. In rat ovaries, there are two main types of CL: newly formed ones due to the current ovulation (new CL), and CL remaining from prior estrous cycles (old CL). In the luteal regression process, CL were almost fully regressed after four estrous cycles in Sprague-Dawley rats. P4 secretion from CL in rodents is regulated by the balance between synthesis and catabolism. In general, luteal toxicity should be evaluated by considering antemortem and postmortem data. Daily vaginal smear observations provided useful information on luteal toxicity. In histopathological examinations, not only the ovaries and CL but also other related tissues and organs including the uterus, vagina, mammary gland, and adrenal glands, must be carefully examined for exploring luteal changes. In this review, histological and functional characteristics of CL in rats are summarized, and representative luteal toxicity changes are presented for improved luteal toxicity evaluation in preclinical toxicity research.
黄体(CL)是排卵后在卵巢中形成的内分泌腺,分泌类固醇激素黄体酮(P4)。P4在发情和月经周期、着床和妊娠中起着关键作用。啮齿动物的不完全发情周期稳定持续4-5天,在每个发情周期阶段都可以区分其形态特征。在大鼠卵巢中,CL主要有两种类型:由于当前排卵而新形成的CL(新CL)和先前发情周期遗留的CL(旧CL)。在黄体退化过程中,Sprague-Dawley大鼠在四个发情周期后CL几乎完全退化。啮齿类动物CL的P4分泌受合成和分解代谢之间的平衡调节。一般来说,黄体毒性应通过考虑尸检和死后数据进行评估。每天的阴道涂片观察提供了关于黄体毒性的有用信息。在组织病理学检查中,不仅要仔细检查卵巢和CL,还要仔细检查其他相关组织和器官,包括子宫、阴道、乳腺和肾上腺,以探索黄体变化。本文综述了CL在大鼠体内的组织学和功能特征,并提出了具有代表性的黄体毒性变化,以改进临床前毒性研究中的黄体毒性评估。
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引用次数: 4
Lipomatosis of axillary lymph nodes in a cynomolgus monkey (Macaca fascicularis) 食蟹猴腋窝淋巴结脂肪瘤病的研究
IF 1.2 4区 医学 Q4 PATHOLOGY Pub Date : 2021-11-15 DOI: 10.1293/tox.2021-0054
M. Nakagawa, S. Hayashi, S. Matsuo, Masaki Yamazaki, A. Kato
Lipomatosis of lymph nodes is defined as the replacement of the lymphatic parenchyma by adipose tissue which grows in the node from the hilus toward the cortical zone. In humans, it is considered as part of the normal aging process and is common in obese patients, but there are no reports in non-human primates. In this report, we describe the first case of lymph node lipomatosis in the bilateral axillary lymph nodes of a young adult cynomolgus monkey. Macroscopically, there were no apparent abnormalities in the axillary lymph nodes on either side, and their volumes were unchanged. At the cut surface, pale yellow fat-like tissue was observed in the medullary area. Histopathologically, well differentiated adipocytes replaced a large part of the lymphatic parenchyma in the area from the hilus to the medulla without any malignant findings. Based on these findings, the patient was diagnosed with lipomatosis of the lymph nodes.
淋巴结脂肪化是指淋巴结内从淋巴结门向皮层区生长的脂肪组织取代淋巴实质。在人类中,它被认为是正常衰老过程的一部分,在肥胖患者中很常见,但在非人类灵长类动物中没有报道。在这个报告中,我们描述了第一例淋巴结脂肪瘤病在双侧腋窝淋巴结的年轻成年食蟹猴。宏观上,两侧腋窝淋巴结未见明显异常,体积未见变化。切面髓质区可见浅黄色脂肪样组织。组织病理学上,分化良好的脂肪细胞取代了从肾门到髓质的大部分淋巴实质,未见任何恶性病变。基于这些发现,患者被诊断为淋巴结脂肪瘤病。
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引用次数: 1
Porencephaly with an optic organ abnormality in a beagle dog 比格犬伴有视觉器官异常的脑孔畸形
IF 1.2 4区 医学 Q4 PATHOLOGY Pub Date : 2021-10-25 DOI: 10.1293/tox.2021-0039
Osamu Hashiguchi, Yuko Yamaguchi, S. Ikezaki, Tsubasa Saito, Saori Igura, Ryo Hirai, N. Horiuchi, K. Tamura
A female TOYO beagle dog showed porencephaly and visual organ abnormalities. At necropsy, there was a cavity filled with cerebrospinal fluid in the right cerebral hemisphere and an adhesion area between the cerebral cortex and the skull, which was partially thickened. Additionally, the right optic nerve showed a slight decrease in diameter. Histopathological examination revealed increased glial fibers and collagen fibers, hemosiderin deposition, and an increased number of microglia in the adhesion area, along with a marked reduction of the cerebral parenchyma. In the right eyeball, the retina and optic nerve showed focal atrophy in the nerve fiber layer and inner granular layer to full retinal atrophy and hypoplasia of the myelinated nerve fibers, respectively. Electron microscopic examination revealed hypoplasia of the myelin sheath of nerve fibers in the right optic nerve. This is an extremely rare case of porencephaly and congenital optic nerve hypoplasia, along with independent retinal thinning.
一只雌性东洋比格犬出现脑孔和视觉器官异常。尸检时,右侧大脑半球有一个充满脑脊液的空腔,大脑皮层和头骨之间有一个部分增厚的粘连区。此外,右侧视神经的直径略有减小。组织病理学检查显示,胶质纤维和胶原纤维增加,含铁血黄素沉积,粘附区小胶质细胞数量增加,脑实质明显减少。在右眼球中,视网膜和视神经分别表现为神经纤维层和内颗粒层的局灶性萎缩至视网膜完全萎缩和有髓鞘神经纤维发育不全。电镜检查显示右侧视神经的神经纤维髓鞘发育不全。这是一种极为罕见的脑孔和先天性视神经发育不全,伴有独立性视网膜变薄的病例。
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引用次数: 1
A case of spontaneous autoimmune skin disease in a cynomolgus monkey (Macaca fascicularis) 食蟹猴自发性自身免疫性皮肤病1例
IF 1.2 4区 医学 Q4 PATHOLOGY Pub Date : 2021-10-16 DOI: 10.1293/tox.2021-0048
Shinichi Onishi, M. Nakagawa, S. Matsuo, J. Shinozuka, Mio Hiramatsu, Takehito Isobe, Toshihiko Watanabe, A. Kato
Pemphigus is an autoimmune blistering disease characterized by lesions on the skin and mucous membranes. To date, no spontaneous cases of this disease have been reported in cynomolgus monkeys. This report describes the histopathological characteristics of spontaneous pemphigus in a cynomolgus monkey. Macroscopically, redness and scaling with pruritus were observed on the skin of the entire body. Histopathologically, the epidermis showed intercellular edema, and eosinophils and mononuclear cells infiltrated the epidermis. There was no obvious acantholysis in the epidermis. The perivascular area showed edema, and eosinophils and mononuclear cells infiltrated the vessels in the dermis. Immunohistochemically, the intercellular area in the epidermis was positive for Immunoglobulin G and Complement component 3. Serologically, anti-desmoglein 1 and desmoglein 3 antibodies in the serum were negative. From these findings, this case was diagnosed as an autoimmune skin disease, suspected to be pemphigus, and concluded as lesions being similar to those in human “pemphigus herpetiformis”.
天疱疮是一种以皮肤和粘膜病变为特征的自身免疫性起泡疾病。迄今为止,在食蟹猴中没有自发性病例的报告。本报告描述了食蟹猴自发性天疱疮的组织病理学特征。宏观上,观察到全身皮肤发红、结垢并伴有瘙痒。组织病理学表现为表皮细胞间水肿,嗜酸性粒细胞和单核细胞浸润表皮。表皮未见明显棘松现象。血管周围水肿,嗜酸性粒细胞和单核细胞浸润真皮层血管。免疫组化结果显示,表皮细胞间区免疫球蛋白G和补体成分3阳性。血清学结果显示,血清抗粘粒蛋白1和抗粘粒蛋白3抗体均为阴性。根据这些发现,本病例被诊断为一种自身免疫性皮肤病,怀疑为天疱疮,并得出结论,病变与人类“疱疹样天疱疮”相似。
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引用次数: 0
Confounders for kidney carcinogenesis in rodent cancer bioassays 啮齿动物癌症生物检测中肾癌发生的混杂因素
IF 1.2 4区 医学 Q4 PATHOLOGY Pub Date : 2021-10-14 DOI: 10.1293/tox.2021-0000
G. Hard
In the long-term safety testing of chemicals for carcinogenicity the toxicologist needs to be aware of a number of scenarios where renal tubule tumors, or their precursors, arise that are not due to a carcinogenic action of the test article. Situations producing false positive results in the kidney include exacerbation of chronic progressive nephropathy (CPN) in rats, confusion of atypical tubule hyperplasia (the obligate precursor of renal tubule tumor) with foci of benign CPN-related renal tubule cell proliferation, inclusion of spontaneous tumor entities, such as the amphophilic-vacuolar tumor, in the test article tumor count, the possibility of a link between spontaneous forms of tubule dilatation and renal tubule tumor formation in mice, and the supposed predictivity of chemically-induced karyomegaly for renal carcinogenicity in both rats and mice. Examples of these misleading situations are described and discussed.
在化学品致癌性的长期安全性测试中,毒理学家需要意识到肾小管肿瘤或其前体的出现并非由于供试品的致癌作用。在肾脏中产生假阳性结果的情况包括大鼠慢性进行性肾病(CPN)的恶化,非典型肾小管增生(肾小管肿瘤的专性前体)与良性CPN相关肾小管细胞增殖灶的混淆,在供试品肿瘤计数中包括自发性肿瘤实体,如嗜两性空泡肿瘤,自发形式的肾小管扩张与小鼠肾小管肿瘤形成之间存在联系的可能性,以及化学诱导的巨核对大鼠和小鼠肾脏致癌性的预测性。对这些误导性情况的例子进行了描述和讨论。
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引用次数: 1
Evaluation of Caspase-3 and Ki-67 expression in squamous cell hyperplasia of the stomach induced by Platycodi radix water extract in Sprague–Dawley rats 桔梗水提物诱导大鼠胃鳞状细胞增生过程中Caspase-3和Ki-67的表达
IF 1.2 4区 医学 Q4 PATHOLOGY Pub Date : 2021-10-09 DOI: 10.1293/tox.2021-0003
Yinghua Li, Seung-Beom Cha, Youngil Park, Bo-Ho Gong, Inae Jeong, H. Kim, Min-Soo Kang, Young-Suk Kim, Chang Hoon Han, Hyun-Kul Lee, Si-Whan Song, C. Park, B. Kang
Platycodi radix is widely used in traditional herbal medicine for the treatment of bronchitis, asthma, pulmonary tuberculosis, hypertension, hyperlipidemia, and diabetes. This study aimed to investigate cell proliferation (Ki-67) and apoptosis (Caspase-3) potential in squamous cell hyperplasia of the stomach induced by a Platycodi radix water extract in a subchronic toxicity study. One hundred formalin-fixed, paraffin-embedded stomach tissues of rats treated with Platycodi radix at doses of 0, 500, 1,000, and 3,000 mg/kg body weight/day were used for the analysis. They were conventionally stained using hematoxylin and eosin (H&E) and immunohistochemically (IHC) stained using caspase-3 and Ki-67 antibodies. The incidence of squamous cell hyperplasia was significantly increased in the 3,000 mg/kg b.w./day treatment group in both sexes (p<0.01). However, the hyperplastic change was completely repaired after 4 weeks of recovery period. Ki-67 expression was similar in all groups, with no statistically significant differences among the groups. Caspase-3 expression was significantly increased in both sexes in the 3,000 mg/kg b.w./day treatment group (p<0.01), compared with the vehicle control groups, and then reduced to normal levels in the recovery groups in both sexes. In conclusion, this study showed that squamous cell hyperplasia induced by the Platycodi radix water extract in the limiting ridge of the stomach is not considered to be abnormal proliferative change; as a result, squamous cell hyperplasia is considered to be a non-adverse effect when induced by the oral administration of the Platycodi radix water extract once daily for 13 weeks in rats.
桔梗在传统中药中被广泛用于治疗支气管炎、哮喘、肺结核、高血压、高脂血症和糖尿病。本研究的目的是在亚慢性毒性研究中探讨桔黄水提取物诱导胃鳞状细胞增生的细胞增殖(Ki-67)和凋亡(Caspase-3)潜能。取100只经福尔马林固定、石蜡包埋的大鼠胃组织,分别以0、500、1000、3000 mg/kg体重/天的剂量给药。用苏木精和伊红(H&E)常规染色,用caspase-3和Ki-67抗体免疫组织化学(IHC)染色。3000 mg/kg体重/天处理组鳞状细胞增生的发生率显著高于对照组(p<0.01)。恢复期4周后,增生性改变完全修复。Ki-67在各组间表达相似,组间差异无统计学意义。在3000 mg/kg体重/天处理组中,Caspase-3的表达量与对照相比显著升高(p<0.01),在恢复组中,Caspase-3的表达量降至正常水平。综上所述,本研究认为桔梗水提物诱导的胃限定脊鳞状细胞增生不属于异常增生性改变;因此,在大鼠中,每天口服一次桔梗水提取物,连续13周诱导鳞状细胞增生,被认为是非不良反应。
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引用次数: 2
Spontaneous well-differentiated pancreatic islet cell carcinoma with vascular invasion in a male F344 rat 雄性F344大鼠自发性高分化胰岛细胞癌伴血管浸润
IF 1.2 4区 医学 Q4 PATHOLOGY Pub Date : 2021-10-08 DOI: 10.1293/tox.2021-0037
Shiori Fujiwara, Y. Yamaguchi, Tsubasa Saito, T. Nakazawa, K. Tamura
This case report describes a case of spontaneous pancreatic islet cell carcinoma with vascular invasion in a 110-week-old male F344 rat. Histologically, a pancreatic nodule consisting of tumor cells and many blood-rich vessels, and covered with a fibrous capsule showed local invasion in the capsule and adjacent acinar tissues, encircling a large duct-like structure (DS). The tumor was composed of well-differentiated tumor cells resembling normal pancreatic islet cells, which had small round nuclei and eosinophilic cytoplasm. Mitotic figures were rare. Immunohistochemistry revealed that the tumor cells were positive for insulin. Although endothelial cells were not detected, the DS wall showed cells positive for α-smooth muscle actin and elastic fibers, suggesting that the DS is the pancreatic artery. This is a rare case of islet cell carcinoma consisting of well-differentiated tumor cells with invasion of the pancreatic artery in a rat.
本病例报告描述了一例110周龄雄性F344大鼠自发性胰岛细胞癌伴血管浸润的病例。组织学上,胰腺结节由肿瘤细胞和许多富含血液的血管组成,并被纤维包膜覆盖,在包膜和邻近的腺泡组织中显示局部浸润,包围着一个大的导管状结构(DS)。肿瘤由与正常胰岛细胞相似的分化良好的肿瘤细胞组成,核小而圆,胞浆嗜酸性。有丝分裂象很少见。免疫组化显示肿瘤细胞胰岛素阳性。虽然未检出内皮细胞,但DS壁可见α-平滑肌肌动蛋白和弹性纤维阳性细胞,提示DS为胰腺动脉。这是一例罕见的大鼠胰岛细胞癌,由分化良好的肿瘤细胞组成,并侵犯胰腺动脉。
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引用次数: 0
A 13-week subchronic toxicity study of 2-(l-menthoxy)ethanol in F344 rats. 2-(l-薄荷氧基)乙醇对F344大鼠13周的亚慢性毒性研究。
IF 1.2 4区 医学 Q4 PATHOLOGY Pub Date : 2021-10-01 Epub Date: 2021-06-03 DOI: 10.1293/tox.2020-0091
Takeshi Toyoda, Kohei Matsushita, Hirotoshi Akane, Tomomi Morikawa, Kumiko Ogawa

2-(l-Menthoxy)ethanol has been frequently employed as a flavoring agent; however, data regarding 2-(l-menthoxy)ethanol toxicity remain limited. We performed a 13-week subchronic toxicity study of 2-(l-menthoxy)ethanol in male and female F344 rats, with doses of 0, 15, 60, or 250 mg/kg body weight (BW)/day orally administered by gavage using corn oil as the vehicle. No significant toxicological changes in general condition, body weight, or food intake were observed in any groups. The hematological assessment showed decreased hemoglobin, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin and increased platelet count in the male 250 mg/kg group. Serum biochemistry revealed elevated total cholesterol in the 250 mg/kg group of male and female rats, reduced triglyceride in the female 250 mg/kg group, and increased total protein in the male 250 mg/kg group, indicating effects on lipid metabolism and protein synthesis. For organ weights, absolute and relative weights of the liver and adrenal glands were increased in the 250 mg/kg group of both sexes and the male 250 mg/kg group, respectively. Histopathological analysis showed chronic nephropathy in the male 15 mg/kg or higher groups, with increased absolute and relative kidney weights, as well as elevated serum creatinine, in the male 60 and 250 mg/kg groups. However, eosinophilic granules containing α2u-globulin were identified in proximal tubules, suggesting α2u-globulin nephropathy specific to male rats and without toxicological significance. These results indicated that the no-observed-adverse-effect level of 2-(l-menthoxy)ethanol was 60 mg/kg BW/day for both sexes.

2-(l-薄荷氧基)乙醇经常被用作调味剂;然而,关于2-(l-薄荷氧基)乙醇毒性的数据仍然有限。我们对雄性和雌性F344大鼠进行了为期13周的亚慢性毒性研究,剂量分别为0、15、60或250 mg/kg体重/天,以玉米油为载体灌胃给药。在任何组中,一般情况、体重或食物摄入量均未观察到明显的毒理学变化。血液学检查显示男性250 mg/kg组血红蛋白、红细胞压积、平均红细胞体积、平均红细胞血红蛋白和血小板计数均下降。血清生化结果显示,250 mg/kg组雄性和雌性大鼠总胆固醇升高,250 mg/kg组雌性大鼠甘油三酯降低,250 mg/kg组雄性大鼠总蛋白升高,提示其对脂质代谢和蛋白质合成有影响。在器官重量方面,250 mg/kg组和雄性250 mg/kg组的肝脏和肾上腺的绝对重量和相对重量分别增加。组织病理学分析显示,男性15 mg/kg或更高剂量组出现慢性肾病,男性60和250 mg/kg组的绝对和相对肾脏重量增加,血清肌酐升高。然而,在近端小管中发现含有α2u-球蛋白的嗜酸性颗粒,提示α2u-球蛋白肾病是雄性大鼠特有的,没有毒理学意义。上述结果表明,2-(l-薄荷氧基)乙醇对两性均为60 mg/kg体重/天,未观察到不良反应。
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引用次数: 1
Safety and efficacy of sFilm-FS, a novel biodegradable fibrin sealant, in Göttingen minipigs. 新型可生物降解纤维蛋白密封剂sFilm-FS在Göttingen微型猪中的安全性和有效性。
IF 1.2 4区 医学 Q4 PATHOLOGY Pub Date : 2021-10-01 Epub Date: 2021-07-10 DOI: 10.1293/tox.2021-0030
Yuval Ramot, Michal Steiner, Yossi Lavie, Nati Ezov, Orgad Laub, Eran Cohen, Yotam Schwartz, Abraham Nyska

Bleeding during surgical procedures is a common complication. Therefore, hemostatic agents have been developed to control bleeding, and fibrin sealants have several benefits. sFilm-FS is a novel fibrin sealant that comprises a biodegradable co-polymeric film embedded with human fibrinogen and thrombin. Herein, the safety and efficacy of sFilm-FS were compared using a liver and spleen puncture model of Göttingen minipigs with those of the standard hemostatic techniques (control animals) and EVARREST®, a reference fibrin sealant. Hemostasis and reduced blood loss were more effectively achieved with sFilm-FS than with the standard techniques in the control animals and comparable to those achieved with EVARREST®. No treatment-related adverse effects were observed in any of the groups. Histopathological evaluation indicated that sFilm-FS was slightly and moderately reactive at the liver puncture site and spleen, respectively, compared with the standard techniques in the control animals. These changes are expected degradation reactions of the co-polymeric film and are not considered as adverse events. No treatment-related abnormalities were noted in the other evaluated organs. Additionally, no evidence of local or systemic thromboses was noted. These results support the use of sFilm-FS for hemostasis in humans.

手术过程中出血是一种常见的并发症。因此,已经开发出止血剂来控制出血,纤维蛋白密封剂有几个好处。sFilm-FS是一种新型的纤维蛋白密封剂,它包含一种生物可降解的共聚膜,内含人纤维蛋白原和凝血酶。本文将sFilm-FS与标准止血技术(对照动物)和EVARREST®(一种参考纤维蛋白密封剂)的安全性和有效性进行比较,并采用Göttingen迷你猪肝脾穿刺模型。在对照动物中,sFilm-FS比标准技术更有效地实现了止血和减少失血,与EVARREST®的效果相当。在任何组中均未观察到与治疗相关的不良反应。组织病理学评价显示,与对照动物的标准技术相比,sFilm-FS在肝脏穿刺部位和脾脏分别有轻微和中度反应。这些变化是共聚膜预期的降解反应,不被认为是不良事件。其他被评估器官未发现与治疗相关的异常。此外,没有发现局部或全身血栓形成的证据。这些结果支持sFilm-FS用于人类止血。
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引用次数: 3
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Journal of Toxicologic Pathology
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