Imaging characteristics of papillary renal cell carcinoma by computed tomography scan and magnetic resonance imaging

AIM: To analyse the differences in the patterns between clear and papillary renal cell carcinomas using magnetic resonance imaging (MRI) and dual-phase helical computed tomography (CT). METHODS: We examined seven patients with papillary renal cell carcinoma, and six with clear cell carcinoma. The highest attenuation value of tumors in the corticomedullary phase (CMP) and the excretory phase (EP) was measured using the observer-defined region of interest (ROI). MRI consisted of T1-weighted and T2-weighted spin-echo imaging. RESULTS: All five tumors except for one with papillary renal cell carcinoma showed homogenous hypointensity, but all six tumors with clear cell carcinoma showed heterogeneous hyperintensity on their T2-weighted images. In the CMP, the mean CT numbers of the papillary renal cell carcinomas were significantly lower than those of the clear cell carcinomas. The mean enhancement of the papillary renal cell carcinomas in the CMP and the EP was significantly lower than that of the clear renal cell carcinomas. The mean CT numbers of the clear cell carcinomas in the CMP were markedly increased from those on the unenhanced CT; those in the EP were decreased gradually. But the mean CT numbers of the papillary renal cell carcinomas in the EP were still slightly more increased than those in the CMP. The enhancement patterns of the papillary renal cell carcinomas in the CMP and the EP were homogenous, but those of the clear cell carcinomas were heterogeneous. CONCLUSIONS: We can speculate the differential diagnosis from clear to papillary renal cell carcinoma using MRI and dual-phase helical CT.     

星点设计-效应面法优化盐酸美金刚缓释微丸处方

目的:采用星点设计-效应面法优化盐酸美金刚微丸的缓释包衣处方.方法:以苏丽丝缓释包衣液中致孔剂的比例(A)和包衣增重(B)为考察因素,以药物在2、4、8、16 h的累积释放度为考察指标,进行多元线性回归和二次、三次多项式回归,建立指标与因素之间的函数关系,并绘制效应面和等高线图,等高线图重合区即为最佳处方区域,在此区域内选取一点验证,并计算自制药和原研药的f2相似因子.结果:星点设计-效应面法确定自变量的最优区域为致孔剂比例14.0%~18.0%,包衣增重4.5%~7.7%.结论:星点设计-效应面法优化盐酸美金刚缓释微丸包衣处方具有良好的预测性.自研制剂与原研药体外释放行为相似(f2>50).     

依据ABCB1基因型及血栓弹力图检测1例PCI术后患者抗血小板聚集个体化治疗

1例53岁男性患者接受经皮冠状动脉介入术后,给予阿司匹林0.1 g·d-1和氯吡格雷75 mg·d-1双联抗血小板聚集治疗.术后第5天发生胸痛,心电图示广泛心肌梗死.临床药师建议行基因与血栓弹力图检测.基因检测提示:细胞色素P4502C19*2(AA)、CYP2C19*3(GG)、CYP2C19*17(CC)、对氧磷酶1(AA)、三磷酸腺苷黏合转运体B1(CT).血栓弹力图检测显示:二磷酸腺苷诱导的血小板聚集抑制率(IPAADP)为24.1%.药师建议以替格瑞洛和阿司匹林治疗.第13天复查血栓弹力图为IPAADP 94.2%,冠状动脉造影示支架内未见狭窄病变.患者未再出现胸闷、胸痛等症状.     

Macrophage-derived SHP-2 inhibits the metastasis of colorectal cancer via Tie2-PI3K signals

This research aimed to explore the influence of Src homology-2 containing protein tyrosine phosphatase (SHP- 2) on the functions of tyrosine kinase receptors with immunoglobulin and EGF homology domains 2 (Tie2)-expressing monocyte/macrophages (TEMs) and the influence of the angiopoietin(Ang)/Tie2-phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) (Ang/Tie2-PI3K/Akt/mTOR) signaling pathway on the tumor microvascular remodeling in an immunosuppressive microenvironment. In vivo, SHP-2- deficient mice were used to construct colorectal cancer (CRC) liver metastasis models. SHP-2-deficient mice had significantly more metastatic cancer and inhibited nodules on the liver surface than wild-type mice, and the high-level expression of p-Tie2 was found in the liver tissue of the macrophages’ specific SHP-2-deficient mice (SHP-2MACKO) + planted tumor mice. Compared with the SHP-2 wild type mice (SHP-2WT) + planted tumor group, the SHP-2MAC-KO + planted tumor group experienced increased expression of p-Tie2, p-PI3K, p-Akt, p-mTOR, vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2), matrix metalloproteinase 2 (MMP2), and MMP9 in the liver tissue. TEMs selected by in vitro experiments were co-cultured with remodeling endothelial cells and tumor cells as carriers. It was found that when Angpt1/2 was used for stimulation, the SHP-2MAC-KO + Angpt1/2 group displayed evident increases in the expression of the Ang/Tie2-PI3K/Akt/mTOR pathway. The number of cells passing through the lower chamber and the basement membrane and the number of blood vessels formed by cells compared with the SHP-2WT + Angpt1/2 group, while these indexes were subjected to no changes under the simultaneous stimulation of Angpt1/2 + Neamine. To sum up, the conditional knockout of SHP-2 can activate the Ang/Tie2-PI3K/Akt/mTOR pathway in TEMs, thereby strengthening tumor micro angiogenesis in the microenvironment and facilitating CRC liver metastasis.     

Multiple Subepidermal Calcified Nodules on the Thigh Mimicking Molluscum Contagiosum

Abstract: Subepidermal calcified nodule (SCN) is a rare form of calcinosis cutis that presents as a solitary verrucous nodule on the face. Here, we report an unusual case of SCN. A healthy 2‐year‐old boy presented with multiple, round, hard, yellow‐white to erythematous lesions on his right thigh. Histopathologic examination of a punch biopsy specimen revealed deposition of calcium in the dermis.     

Circulating Toll‐like receptor (TLR) 2, TLR4, and regulatory T cells in patients with chronic hepatitis C

Wang J‐P, Zhang Y, Wei X, Li J, Nan X‐P, Yu H‐T, Li Y, Wang P‐Z, Bai X‐F. Circulating Toll‐like receptor (TLR) 2, TLR4, and regulatory T cells in patients with chronic hepatitis C. APMIS 2010; 118: 261–70. The mechanism of hepatitis C virus (HCV) involvement in innate immune responses and immune modulation has not been well characterized. In the present work, we studied Toll‐like receptor (TLR) 2 and TLR4, which were recently recognized as the important components of innate immunity, as well as CD4⁺ CD25⁺ CD127^low/? regulatory T cells (Tregs), which actively suppress pathological and physiological immune response during HCV infection. The study involved 31 chronic hepatitis C patients and 20 healthy controls. TLR2 and TLR4 expression in peripheral blood monocytes and the number of Tregs were examined by flow cytometric analysis. Overexpression of TLR2 and TLR4 was found in chronic hepatitis C patients as compared with controls. Furthermore, increased cytokine production, including that of β‐interferon, tumor necrosis factor‐α, interleukin (IL)‐6, and IL‐8, was observed in peripheral blood mononuclear cells from chronic hepatitis C patients after challenge with TLR2 and TLR4 agonists. The number of Tregs was significantly higher in chronic hepatitis C patients and the increased Tregs were associated with HCV genotype 1b. In vitro studies demonstrated that circulating Tregs suppress T‐cell responses in chronic hepatitis C patients. Significant correlations were found between the viral load and Treg number and between TLR2 and TLR4 level in chronic hepatitis C patients. Taken together with other published data, these results suggest that TLR2, TLR4, and Tregs correlate closely with chronic HCV infection.     

脉冲电流穴位刺激对脂肪肝患者肝血液动力学的影响

目的:探讨经皮的肝脏附近穴位脉冲电流局部刺激对脂肪肝患者肝血流量的影响。方法:利用图像处理系统对31树脂肪肝患者脉冲电流刺激前后彩色多普勒能量图图象进行单盲量化处理(取肝脏血流的彩色像素总面积SC-PA、平均彩色亮度值ACV和两者的积分SCPA×ACV3项指标),对所得数据进行自身前后配对统计分析。结果:SCPA个体间的差异较大,脉冲刺激后增大的略占多数,t=2.71,P=0.0109;ACV脉冲刺激前后差异稍大,并且以脉冲刺激后稍高的为多,t=3.42,P=0.0018;综合两因素的积分值(SCPA×ACV)刺激前后的差异则较为明显,t=8.15,P<0.0001。结论:适当的经皮肝脏附近穴位脉冲电流刺激可以改善脂肪肝患者肝脏血流供应情况。     

Mucosal mast cell counts correlate with visceral hypersensitivity in patients with diarrhea predominant irritable bowel syndrome

Background and Aim: Although increased mast cells in the gut and their role in visceral hypersensitivity in irritable bowel syndrome have been postulated, this relationship remains unclear. Our aim was to determine whether a relationship exists between the number of mucosal mast cells in the gut and visceral hypersensitivity. Method: Eighteen patients with diarrhea predominant irritable bowel syndrome (D‐IBS) (eight females, 10 males aged 25–65 years; mean 42.6 years) with symptoms meeting the Rome‐II criteria, and 15 healthy controls (five females, 10 males aged 31–57 years; mean 41.4 years) were recruited. Participants completed a questionnaire for bowel symptoms and psychological distress. Colonic mucosal mast cells were identified immunohistochemically and quantified by image analysis, and maximally tolerable pressures were evaluated using barostat test. Results: Numbers of mast cells were significantly greater in the terminal ileum, ascending colon and rectum of D‐IBS patients compared with controls (P < 0.01). A multivariate analysis of the barostat test showed that maximally tolerable pressures of D‐IBS patients were significantly lower than those of controls (P < 0.01). When patients were divided into the rectal hypersensitivity (+) and (–) groups by the distension level of 34 mmHg, mast cell counts were significantly higher in the rectal hypersensitivity (–) group than in the rectal hypersensitivity (+) group for the terminal ileum, ascending colon and rectum (P < 0.05, respectively). Conclusions: Rectal sensitivity was enhanced in D‐IBS patients with moderately increased mucosal mast cells, but it was attenuated in patients with markedly increased ones. This study might provide evidence for an important role of mast cells in visceral hypersensitivity.     

Analysis of the CDR3 region of alpha/beta T‐cell receptors (TCRs) and TCR BD gene double‐stranded recombination signal sequence breaks end in peripheral blood mononuclear cells of T‐lineage acute lymphoblastic leukemia

Recently, numerous reports have highlighted the restriction of the CDR3 length of T‐cell receptor (TCR) beta chain in T‐cells infiltrating solid tumors and hematological malignancies. However, these studies ignored the restriction of CDR3 length of TCR alpha chain and few of them attempted to reveal the mechanisms of the oligo‐clonal expansion of T cells in the tumors. The primary aims of this study were twofold to: (i) analyze the CDR3 length of TCR alpha and beta chain in peripheral blood mononuclear cells of T‐lineage acute lymphoblastic leukemia (T‐ALL); and (ii) discover the relationship between the clonality of T cells and the process of TCR rearrangement in peripheral T cells. To this end, we investigated the TCR BV and TCR AV family spectratypes of two T‐ALL patients and healthy controls using the immunoscope spectratyping technique. We found that the spectratypes exhibited a Gaussian distribution in healthy controls. However, the TCR repertoires of the two patients were highly restricted in the number of different TCR BV and TCR AV family members present. Furthermore, we found that the peripheral blood mononuclear cells (PBMC) of two T‐ALL patients had the recombination signal sequence (RSS) 5′‐ and 3′‐breaks end in the TCR BD2 gene using a specialized ligation‐mediated polymerase chain reaction, implying the ongoing recombination of the TCR beta gene. Analysis of the particular CDR3 length of TCR alpha/beta T cells might be helpful for further study of the individualized therapy of T‐ALL. This information will also be helpful in exploring new immunological pathogenesis and facilitating the design of a T‐ALL vaccine, as well as in improving our understanding of healthy human T‐cell development.