急性髓性白血病(AML)是一种主要发生在老年人的血液系统恶性肿瘤,诊断时的中位年龄为68 岁[1].目前AML的标准治疗包括强化诱导化疗、巩固化疗及造血干细胞移植.然而,由于高龄、合并症多、一般情况差等不利因素,导致部分AML患者不能耐受标准化疗,通常会接受低强度的化疗方案,包括低甲基药物(阿扎胞苷或地西他滨)单药或联合低剂量阿糖胞苷;部分合并脏器功能不全的患者因无法耐受化疗,仅接受最佳支持治疗.

目的 总结原发肝脏细胞淋巴瘤(PHDLBCL)的诊断及治疗方法.方法 回顾性分析1例PHDLBCL的临床资料.结果 患者因上腹部胀痛入院,PET-CT及腹部影像学检查提示肝脏多发占位,有典型的"血管漂浮征",肝脏穿刺活检病理及免疫组化检查提示符合弥漫大B细胞淋巴瘤,确诊为PHDLCL.经VP方案预处理及R-CHOP和GemOx方案诱导缓解巩固后,以来那度胺维持治疗,随访9个月,患者处于完全缓解状态.结论 PHDLBCL症状不典型,影像学的"血管漂浮征"常有提示作用,确诊需要病理学检查.VP方案预处理有利于快速降低瘤负荷,以利妥昔单抗联合多柔比星脂质体的R-CHOP的方案有良好的诱导缓解作用,来那度胺的维持治疗可能会带来生存获益.

髓外浆细胞瘤(extramedullary plasmacytoma,EMP)是一种原发于骨髓造血组织以外,单克隆浆细胞异常增生所致的软组织恶性肿瘤,占浆细胞肿瘤的3％～5％.EMP可发生于任何髓外组织器官,多见于头颈部或上呼吸道,其次为胃肠道,且以单发病灶为主,而原发于胆道的EMP临床罕见,尚未见报道,其临床症状及影像学检查结果与胆总管癌难以鉴别,易被误诊,诊断主要依靠病理检查.本文报告1例原发于胆总管的EMP,并结合文献,探讨此类疾病的治疗策略及转归.

Objective To investigate the causes, treatment options and outcomes of immune thrombocytopenia (ITP) patients with splanchnic venous thrombosis (SVT). Methods The clinical diagnosis, treatment and outcomes data of one 26-year-old male ITP patient with SVT as initial manifestation were collected. The possible causes and treatment options of the patients were discussed through literatures review. Results The result of blood routine tests of the patient showed that Plt（17-38）×109/L and eosinophils (EOS) 46.9%-50.0%. B-ultrasound and CT findings suggested thromboses of splenic vein, hepatic portal vein and its branches were formed, the patient was diagnosed as ITP with SVT. After active etiological treatment and reduced dose of low molecular weight heparin(LMWH) for anticoagulation, the patient recovered. Conclusion ITP combined with large scale of SVT is rare, and it is difficult to cure. It should be pay more attention to the possible thrombosis risk triggered by a transiently increased EOS in the blood stream. Promptly etiological treatment and the balance between anticoagulant therapy and bleeding risks should be taken in clinical practice.

Purpose: To identify the biological function of phosphoserine aminotransferase 1 (PSAT1) in regulating cell proliferation and apoptosis in multiple myeloma (MM).Methods: The mRNA and protein levels of PSAT1 were determined using quantitative real-time polymerase chain reaction (PCR) and western blotting, respectively. Cell proliferation was measured using CCK-8 assay.Results: PSAT1 mRNA and protein expression levels were significantly increased in MM cell lines when compared to control cells. Moreover, downregulation of PSAT1 inhibited MM cell proliferation and induced cell apoptosis, whereas overexpression of PSAT1 promoted MM cell proliferation and suppressed cell apoptosis. Further analysis demonstrated that the underlying mechanism was via regulation of PI3K/AKT pathway.Conclusion: The results identified a novel role for PSAT1 in the progression of MM, which may provide a therapeutic and a new anticancer target for the therapy of MM. Keywords: Multiple myeloma, PSAT1, Cell proliferation, PI3K/AKT pathway

Objective:To investigate the relationship between mitogen-activated protein kinase (MAPK) signaling pathway related signal molecules and the apoptosis of acute promyelocytic leukemia NB4 cells induced by puerariae radix flavones (PRF) and its significance.Methods:The cells were divided into control group [0.025% dimethyl sulfoxide (DMSO) to replace PRF] and 10, 30, 50 μg/ml PRF groups. The proliferation inhibition rate of NB4 cells exposed with PRF for 24, 48 and 72 hours was determined by methyl thiazolyl tetrazolium (MTT) method, and the nuclear morphology was determined by confocal laser scanning microscope after 48 hours. NB4 cells were divided into control group (adding 0.025% DMSO) and 10, 30 and 50 μg/ml PRF with or without 10 μmol/L c-Jun N-terminal kinase (JNK) inhibitor (SP600125) group, and the cells were treated for 48 hours and the changes in the expressions of MAPK pathway related proteins JNK, tumor necrosis factor α (TNF-α), extracellular signal-regulated kinase (ERK) and p38 MAPK were tested by Western blot.Results:10, 30 and 50 μg/ml PRF inhibited the proliferation of NB4 cells in 24, 48 and 72 hours, which was in time- and dose-dependent manners (all P < 0.05). The half-maximal inhibitory concentration (IC 50) at 24, 48 and 72 hours were (40.03±2.23) μg/ml, (22.92±1.72) μg/ml and (17.99±1.48) μg/ml, respectively. The confocal laser scanning microscope showed that NB4 cells displayed distinct apoptotic characteristics after PRF treatment. After co-cultivating NB4 cells with 10 μmol/L SP600125 and different concentrations of PRF for 48 hours, the expression of JNK1 in NB4 cells was suppressed ( P < 0.05), and the expressions of JNK2/3 and p38 MAPK decreased, but the differences were not statistically significant (both P > 0.05). The expressions of ERK1 and ERK2 gradually increased in the single-drug group, while the expression in the combined drug group decreased. The expression of TNF-α in the 50 μg/ml PRF+SP600125 group was down-regulated compared with the 50 μg/ml PRF single-drug group, while the expressions in the 10 and 30 μg/ml PRF+SP600125 groups were up-regulated compared with the 10 and 30 μg/ml PRF single-drug groups. Conclusion:10-50 μg/ml PRF may activate the MAPK signaling pathway through TNF-α. JNK, ERK1/2 and p38 MAPK interact with each other to activate pro-apoptotic related proteins and induce NB4 cells apoptosis.

ABSTRACT Objectives: The great majority of adult patients with immune thrombocytopenia (ITP) who fail to respond to first-line medication or who relapse following response require additional treatment. Although broad guidelines currently exist for second-line and subsequent therapies, none to date have been prescriptive. The purpose of this systematic review and network meta-analysis was to establish a clinically relevant ranking of the efficacy and safety of medications for adults (≥18 years old) with previously treated ITP. Methods: Relevant publications from Medline, Embase, and the Cochrane database were searched from their inceptions through July 31, 2018. The primary outcome was the overall response (OR, defined as a platelet count ≥50 × 109/L at the end of treatment without rescue therapy), while the secondary endpoints included early response (ER; i.e. a platelet count ≥50 × 109/L at week 2 after initiation of treatment) and therapy-related severe adverse events (AEs). Results: Thirteen randomized controlled trials (1,202 patients) were included in this study. According to pooled results, romiplostim appears to be the most suitable treatment in terms of OR, followed by avatrombopag, eltrombopag, fostamatinib, and rituximab. Avatrombopag produced more satisfactory outcomes than romiplostim, eltrombopag, and rituximab in terms of ER; severe AEs profiles were similar across all treatment arms. Conclusion: Romiplostim appears to be the best option for patients who fail to respond to prior treatment or relapse thereafter, while avatrombopag and eltrombopag are reasonable alternatives. Rituximab monotherapy is not recommended, as it produces the lowest OR and ER rates.

Image reconstruction algorithms play an important role in practical applications of electrical capacitance tomography. In the present paper, a combined image reconstruction method is proposed, which takes the results of Landweber algorithm as the constraint condition of Tikhonov algorithm's regularization parameter, calculates the regular parameter, inverts the inverse matrix of sensitivity matrix, and finally obtains the dielectric constant distribution; thus, reconstructed images with improved clarity were obtained. Simulation test are carried out to evaluate and analyze the proposed method from image error, correlation coefficient, image reconstruction time, and anti-noise ability. The results revealed that the Tikhonov regularization algorithm had excellent anti-noise ability; thus, it significantly improved the clarity of reconstructed images and clearly distinguished the multi-phase flow pattern and distribution.

Context Curcumin, a polyphenolic compound extracted from the rhizome of the tropical plant Curcuma longa L. (Zingiberaceae), has been considered as a cancer chemopreventive drug by American National Cancer Institute. Objective To examine the effect of curcumin on acute monocytic leukaemia SHI-1 cells in vivo. Materials and methods The SHI-1 cells (1 × 106 cells in 0.1 mL PBS) were injected subcutaneously into the right flanks of the female SCID mice. Curcumin dissolved in olive oil (15 and 30 mg/kg) was administered (i.p.) to mice once a day for 15 days while the control group received olive oil injection. Tumour proliferation and apoptosis were examined by PCNA, TUNEL and cleaved caspase-3 staining. The expression of MAPK, NF-κB, MMP9, MMP2 and vimentin were confirmed by RT-PCR, immunohistochemistry or western blotting. Results Administration of curcumin significantly inhibited tumour growth, as the tumour weight decreased from 0.67 g (control) to 0.47 g (15 mg/kg) and 0.35 g (30 mg/kg). Curcumin inhibited the expression of PCNA and increased the degree of TUNEL and cleaved caspase-3 staining in tumour tissue. The results of western blotting showed that curcumin treatment inhibited NF-κB and ERK signalling while activating p38 and JNK. Moreover, curcumin attenuated the mRNA transcription and protein expression of MMP2 and MMP9. Curcumin also suppressed the level of vimentin. Discussion and conclusions Our study demonstrates that curcumin can inhibit the growth and invasion of human monocytic leukaemia in vivo, suggesting the possible use of curcumin for anti-metastasis in leukaemia and the value of determining its unique target.

OBJECTIVE:To investigate the effects of oridonin (ORI) on the proliferation and apoptosis of human multiple myeloma cell line H929 and its possible mechanism.METHODS:H929 cells were exposed to ORI 0、4、8、12、16、20、24、28、32 μmol/L for 12, 24 and 36 hours respectively. The prolifcration inhibitory effect of ORI on H929 cells was determined by MTT assay and then the working concentrations of ORI were determined. The morphological changes and apoptosis of H929 cells were observed by TUNEL (TdT-mediated dUTP Nick-End Labeling) and fluorescence microscopy. The apoptosis rate of H929 cells was detected by flow cytometry with Annexin V-FITC/PI staining. The protein expressions of pro-caspase-3, BCL-2，p-PI3K, p-Akt, BAX, Cleaved PARP and p-JNK, p-ERK and p-p38 in H929 cells were detected by Western blot.RESULTS:Compared with the control group, the proliferation of H929 cells treated with the ORI of 8-16 μmol/L was significantly inhibited and the apoptosis of H929 cells was obviously increased in dose- and time-dependent manners. As for morphological changes, the characteristics of apoptotic cells were presented in H929 cells treated with ORI for 24 hours. The protein levels of pro-caspase-3, BCL-2，p-PI3K, p-Akt were down-regulated with increasing of ORI concentration（r=0.9861, r=0.9725, r=0.9413, r=0.9373）, while the BAX, Cleaved PARP and p-JNK, p-ERK and p-p38 were up-regulated（r=0.9178, r=0.8877, r=0.882, r=0.9645, r=0.8623）.CONCLUSION:The ORI possesses anti-myeloma effects, can inhibit the proliferation and induce the apoptosis of H929 cell line in vitro. Its potential mechanism may be related with up-regulating the MAPK and down-regulating the PI3K/Akt signal pathways.

Abstract The principle model and calibration method of measurement are very important to the measurement system. In the vision measurement system, the auxiliary light source, such as laser, interference light, sine grating and so on, is usually needed in order to achieve high precision measurement results. In the existing 3D measurement methods for the surface topography of complex objects, in order to complete the measurement of absolute phase, it is usually necessary to process at least 6 fringe images, which limits the measurement speed. A method for obtaining the 3D shape of an object by using four sinusoidal fringes is presented. The truncated phase of the sinusoidal fringe is obtained by using the four-step phase shift. When the fringe order is obtained, the time of data processing can be reduced and the measurement speed can be further improved. The reconstruction time is less than two minutes and the maximum absolute error and maximum RMS error are 0.033mm and 0.029mm respectively when the height of the face model is 45mm. The validity and practicability of the method are verified, and it has a wide application prospect in high-speed and real-time 3D measurement of complex topography.

Background: Acute promyelocytic leukaemia (APL) is a special subtype of acute myeloid leukaemia. The aim of this study was to investigate the anti-tumour effects of puerariae radix flavones (PRF), the total flavonoids from Chinese herb puerariae radix (PR), on the human APL cell line NB4 and to explore the potential mechanisms. Methods: NB4 cells were exposed to various concentrations (0, 10, 30, 50 μg/ml) of PRF. Cell viability was measured by MTT assay. The cell cycle, the extent of cell apoptosis and the mitochondrial transmembrane potential were analysed with flow cytometry (FCM). The expression of apoptosis-related proteins was assayed by western blot. Results: We found that PRF inhibited cell viability of NB4 cells in a timeand dose-dependent manner. The cell cycle was arrested in the G0/G1 phase. FCM assays showed that PRF induced apoptosis and decreased mitochondrial membrane potential in a dose-dependent manner. NB4 cells treated with PRF expressed higher levels of cleaved caspase-3, caspase-9 and poly ADP-ribose polymerase (PARP) with an increased Bax/Bcl-2 ratio and Bcl-xL expression. Western blot analysis showed that expression of JNK was significantly lower while the expression of p-JNK was greater. Further analysis showed activation of the JNK pathway of NB4 cells by PRF. Conclusions: Our data, taken together, indicate that PRF exerted a potent anti-tumour effect on NB4 cells by inducing apoptosis, the mechanism of which might be accompanied with the JNK pathway and the mitochondrial pathway activation.

OBJECTIVES:To explore the clinical significance of clonal evolution of additional chromosomal 8 in CML progression.METHODS:An unusual case with the clonal evolution from trisomy 8 to tetrasomy 8 accompanied by 2 time of CML blast crisis (BC) was reported.RESULTS:This patient suffered from 2 time of CML blast crisis and the additional chromosome 8 aberrations were accompanied. Trisomy 8 and tetrasomy 8 were detected at first CML blast crisis and second CML blast crisis, respectively. After tetrasomy 8 was developed, the c-Myc was over-expressed and the central nervous system leukemia happened in this case. Only high dose Ara-C and MTX regimen could induce remission for a short period.CONCLUSION:These findings suggested that additional chromosome 8 aberrations are important marker for poor prognosis of CML patients and contribute to a poor prognosis.

"不仁"又为"麻木",历代多有论述,而张仲景以"营卫阴阳立论",最具临证指导价值,清代医家林珮琴《类证治裁》设立专篇.多发性骨髓瘤治疗相关性周围神经病变,西医尚无确切有效治疗药物和方法,我们认为与药物戕伤,阳气受损,营卫不和,浊邪阻络有关,治重益营卫以使气血充盈,温阳气以使浊邪消散,化痰瘀以使气血畅通,柔肝阴以使筋脉和利.故治拟益气温阳,调和营卫,柔肝舒筋,活血通络.方以黄芪桂枝五物汤、吴茱萸汤、肾气丸、止痉散等加减,可获良效.

Objective To systematically assess the effectiveness and safety of subcutaneous bortezomibin comparison with intravenous bortezomib for treating multiple myeloma.Methods Data from relative clinical trials were from Clinicaltrials.gov and Cochrane Collaboration.A comprehensive literature search was performed from data bases such as PubMed and EmBase.The data of effective and safety on subcutaneous and intravenous administration was comparison.The Meta analyzed by RevMan5.3 Software.Results Three randomized controlled trials (RCT) and 8 retrospective cohort studies(RCS),11 research papers in total met inclusion criteria,including 2021 cases.There were no significant differences between the subcutaneous bortezomib group and the intravenous bortezomib group in the overall responses rate [OR =1.06,95％ CI (0.84,1.33)] and complete response [OR =0.93,95％ CI (0.65,1.31)].In terms of safety,the incidence of peripheral neuropathy and grade ≥3 peripheral neuropathy were significantly lower in subcutaneous bortezomib group than those in intravenous bortezomib group with siginificance [OR =0.44,95％ CI (0.35,0.56);OR =0.30,95％ CI (0.19,0.46),respectively] (P ＜ 0.001).Conclusion Subcutaneous bortezomib is as effective as intravenous bortezomib in multiple myeloma and reduce the incidence of peripheral neuropathy.

Autophagy plays an important role in plasma cell ontogeny and in the pathophysiology of multiple myeloma. Autophagy is usually considered a pro-survival mechanism, and cooperates with the ubiquitin proteasome system in maintaining the homeostasis of myeloma cells by degrading excessive and misfolded proteins for energy recycling. Therefore, the inhibition of autophagy could effectively induce death in myeloma cells, and could synergize with proteasome inhibitors. However, the excessive activation of autophagy could also lead to the extreme degradation of the organelles that induce autophagic cell death. Hence, the activation of autophagic cell death might also represent a promising approach for treating myeloma. Recent studies have demonstrated that autophagy also mediates drug resistance in myeloma cells and the complications of myeloma, while the inhibition of autophagy may reverse the response to drugs. In this study, we have mainly reviewed recent research on autophagy in relationship to the therapeutic effect, the reversal of drug resistance, and the mediation of complications.

Acute promyelocytic leukemia (APL) is a special subtype of acute myeloid leukemia, characterized by the reciprocal chromosomal translocation of t (15;17)(q22;q21), which generates PML-RARαfusion protein. All-trans-retinoic acid (ATRA) and As2O3 could induce APL cells to differentiation and apoptosis, respectively, making APL become the first curable leukemia. Autophagy is one of metabolic mechanisms to maintain cell homeostasis. Recent studies have showed that autophagy plays an important role in the differentiation of APL cells induced by ATRA/As2O3. Meanwhile, autophagy may affect the sensitivity of APL cells to the pro-apoptotic effect of drugs. Therefore, targeting and regulating autophagy might be a new therapeutic approach of APL and even other leukemia in the future. This article will briefly review the advance of autophagy in APL in recent years.

Context: Curcumin is a polyphenolic compound extracted from rhizomes of the tropical plant Curcuma longa L. (Zingiberaceae) and it has antitumor, antioxidative, and anti-inflammatory effects. However, its effects on leukemia cell proliferation and invasion are not clear.Objective: This study investigates the effects of curcumin on acute monocytic leukemia SHI-1 cells at the molecular level.Materials and methods: The effects of SHI-1 cells treated with 6.25-25 mu M curcumin for 12-48h were measured by MTT assay, flow cytometry, and Matrigel transwell assay; the underlying molecular mechanisms were assessed by quantitative PCR, Western blotting, and gelatin zymography.Results: Treatment of SHI-1 cells with curcumin inhibited cell proliferation in a dose- and time-dependent manner, and the IC50 values at 12, 24, and 48h were 32.40, 14.13, and 9.67 mu M. Curcumin inhibited SHI-1 cell proliferation by arresting the cells in the S-phase, increasing the number of Annexin V-FITC+/PI- cells and promoting the loss of Delta Psi(m). The results of PCR and Western blotting showed that curcumin increased the FasL mRNA level; inhibited Bcl-2, NF-kappa B, and ERK expression; and activated P38 MAPK, JNK, and caspase-3. Additionally, curcumin partially suppressed SHI-1 cell invasion and attenuated the mRNA transcription and secretion of MMP-2 and MMP-9.Discussion and conclusion: This study demonstrates that curcumin not only induces SHI-1 cell apoptosis, possibly via both intrinsic and extrinsic pathways triggered by JNK, P38 MAPK and ERK signaling, but also partially suppresses SHI-1 cell invasion, likely by reducing the levels of transcription and secretion of MMP-2 and MMP-9.

Background and Objective: The Src family consists of Src, Lck (p56Lck), Fyn, Hck, Blk, Lyn, Fgr, Yes, and Yrk protein tyrosine kinases, which display cell and tissue specific expression. These non-receptor protein tyrosine kinases regulate many cellular processes including cell growth, differentiation, shape, migration, and survival. p56Lck is primarily expressed in T lymphocytes where it stimulates T cell receptor-mediated signaling to regulate thymocyte development. Similar to other SRC family members, p56Lck activity is negatively regulated by phosphorylation of Tyr505 and undergoes autophosphorylation on Tyr394 in the active state. Our previous studies showed that p56Lck activation occurred in proliferating endothelial cells exposed to cleaved high molecular weight kininogen (HKa), which induced endothelial cell apoptosis.The purpose of this study is to define the role of Lck in regulation of endothelial cell survival and angiogenesis.

临床教学是医学教育的重要组成部分,是医学生的重要过渡环节,需高度重视提高临床教学质量.本文从重视床边教学、注重临床思维、加强技能考核、创新临床教学模式四方面,探索有效教学途径.