The Applications of Mitoxantrone and Its Liposome in Adult Acute Myeloid Leukemia

Acute myeloid leukemia (AML), a rapidly progressing hematopoietic malignancy, can only be cured hopefully by hematopoietic stem cells transplantation (HSCT). Before HSCT, we usually exert effects by attempting certain regimens to induce these tumor cells to death. Administered in AML patients, the classic “3 + 7” intensive induction regimen including anthracyclines and cytarabine is recommended by guidelines worldwide. However, conventional regimens consist of anthracyclines, a category of drug limited by cumulative, dose-related, progressive myocardial damage and congestive heart failure occurs when its total doses break through the cut-off. Based on this background, mitoxantrone (MIT), an anthraquinone, was developed to a new form to reduce cardiotoxicity. Meanwhile, the nanomedicine, mitoxantrone liposome (Lipo-MIT), was characterized by improved bioavailability and limited toxicity. This drug has great therapeutic potential, but different side effects. We conclude the overall history and development of MIT and Lipo-MIT, which show controversial efficacy of MIT compared to doxorubicin and therapeutic potential of Lipo-MIT. This article reviewed the application of MIT and liposome forms in adult AML patients. .

MTZ油田保护油气层钻井液完井液技术

MTZ油田位于高集凹陷北斜坡带西部,构造南翼的Z2断块产层为Ef2和Ef1。Ef2和Ef1砂岩为中低孔中低渗透储层,孔隙压力系数为0.94-0.98,储层属中偏强水敏、极强盐敏、弱速敏,基本无酸敏。根据储层特点及对钻井完井过程中油层损害因素的分析,研究了系统保护油气层技术。系统保护油气层技术包括:选用抑制性强的两性离子聚合物钻井液体系;采用屏蔽暂堵技术,加入3％-4％超细碳酸钙及2％磺化沥青粉(软化点为70-80℃);应用低密度水泥浆(密度为1.47 g/cm3),使用S27降失水剂、SEP-1晶格膨胀剂和CO-124防气窜膨胀剂等外加剂;用PDC四刮刀钻头,加快钻速,缩短浸泡时间;用加有3％聚季胺的防膨液作为射孔液、压井液。在MTZ油田推广应用32口井,取得了较好的经济效益和社会效益。平均每口井浸泡时间缩短8.15 d,平均机械钻速提高32.4％,固井合格率为100％,完井电测一次成功率由60％提高至72％,平均完井作业时间缩短4 d;单井产量至少提高20％,平均采油强度相对提高19.05％,平均日产量提高39.29％。

含米托蒽醌脂质体方案治疗高危儿童急性髓系白血病的临床分析

目的:探讨含米托蒽醌脂质体方案治疗高危儿童急性髓系白血病(AML)的安全性与有效性。方法:收集武汉儿童医院2022年1月至2023年2月应用含米托蒽醌脂质体方案治疗的AML高危患儿为观察组,对照组为应用去甲氧柔红霉素方案的AML高危患儿,分析患儿的临床资料,比较两组患儿治疗后骨髓恢复时间、骨髓完全缓解(CR)率,微小残留病灶(MRD)清除率及治疗相关不良反应等临床特性。结果:患儿接受含米托蒽醌脂质体化疗方案在白细胞(17 vs 21 d)、粒细胞(18 vs 24d)、血小板(17 vs 24 d)及血红蛋白(20 vs 26 d)计数恢复时间上均明显优于去甲氧柔红霉素组(P<0.05)。观察组治疗有效率和MRD转阴率分别为90.9%和72.7%,对照组为94.1%和76.4%,均无显著性统计学差异(P>0.05),两组治疗总有效率类似。结论:含米托蒽醌脂质体化疗方案治疗高危儿童AML疗效不劣于去甲氧柔红霉素方案,但骨髓抑制时间明显缩短,安全性好。

自体荧光联合示踪用盐酸米托蒽醌注射液在甲状腺术中识别甲状旁腺的临床应用

目的:在甲状腺术中,评估近红外自体荧光成像技术(NIRAF)联合示踪用盐酸米托蒽醌注射液(MHI)能否提高甲状旁腺的识别率,从而降低甲状腺术后低钙血症及甲状旁腺功能减退的发生率。方法:前瞻性连续选取2022年10月—2023年3月在潍坊市益都中心医院行甲状腺手术治疗的患者80例,根据入院时间随机将患者分为联合组和对照组,每组40例。联合组术中于甲状腺内注射MHI 0.6 mL并联合NIRAF识别甲状旁腺,对照组仅于术中使用NIRAF。比较两组术前血钙、甲状旁腺激素(PTH)水平,术中甲状旁腺识别准确率、自体移植率,术后甲状旁腺激素(PTH)、血钙水平、甲状旁腺误切率及低钙症状发生率。结果:联合组行甲状旁腺移植术4例(10.0%),对照组12例(30.0%),两组之间差异有统计学意义(χ^(2)=3.828,P=0.049)。联合组甲状旁腺识别准确率高于对照组(98.11%比85.96%,χ^(2)=3.899,P=0.048),且联合组存在误切甲状旁腺2例(5.0%),对照组10例(25.0%),两组对比差异有统计学意义(χ^(2)=4.804,P=0.028)。术后1 d,联合组及对照组血钙水平分别为(2.24±0.11)mmol/L及(2.16±0.17)mmol/L,PTH水平分别为(27.18±11.77)ng/L及(18.57±9.55)ng/L,差异均有统计学意义(P<0.05)。术后3 d,联合组血钙水平为(2.32±0.17)mmol/L,对照组为(2.23±0.12)mmol/L;联合组PTH水平为(33.03±7.88)ng/L,对照组为(24.89±9.29)ng/L;两组差异均有统计学意义(P<0.05)。联合组术后出现手足或口周麻木症状3例(7.5%),对照组10例(25.0%),差异有统计学意义(P=0.034)。结论:自体荧光联合示踪用盐酸米托蒽醌注射液可以有效提高甲状腺术中甲状旁腺识别的准确率,从而避免误切,减少术后低钙血症及甲状旁腺功能减退发生率,降低患者术后手足、口周麻木感的发生,提高患者就医体验。

Lithostructural Control of the Gold Mineralization of the Douta Permit of African Star Resources (Kédougou-Kéniéba Inlier, Southeastern Senegal)

The Douta permit of African Star Resources/Thor Explorations, located in the southeast of Senegal, in the Kédougou-Kéniéba Inlier (western part of the West African Craton), is dominated to the East by metasedimentary formations such as greywackes, shales, graphitic shales, quartzites, cherts, claystones and breccias characteristic of the Dialé-Daléma basin. To the West, the mafic formations of the Mako volcanic belt are the most common. Metasedimentary rocks are associated with metavolcanosedimentary terms found at the contact zones between the two (2) Birimian groups. These different geological formations are cut by mafic dolerite and gabbro sills and/or dykes, as well as quartz and microgranite veins. The Douta gold project is crossed from North to South by the MTZ (Main Transcurrent Zone), generally oriented NE-SW and becoming N-S towards the North. The permit is characterized by several shear corridors. The rocks are affected by brittle, brittle-ductile to ductile deformations. The gold mineralization is hosted by a NE-trending shear corridor called the Makosa corridor (Makosa shear zone), therefore sub-parallel to the MTZ. It has a subvertical dip (75˚ to 85˚ to the NW). It is associated with a hydrothermal phase characterized by quartz-sericite-epidote-fine, disseminated pyrite and arsenopyrite ± albite ± chlorite paragenesis. These minerals testify to the existence of a low degree of metamorphism (greenschist facies, epizonal domain) in the area. However, metamorphism reaches amphibolite facies in some places, particularly in the vicinity of intrusive bodies, with the presence of hornblende (amphiboles) and plagioclase. The gold mineralization is mainly hosted by two (2) metasedimentary lithological units: meta-greywackes and shales.

MTZ油田复杂地质规律研究及开发建议

根据MTZ油田生产实际和油藏动态监测资料 ,对油田复杂地质规律进行深入研究。结果表明 ,造成注采矛盾 ,影响开发效果的主要原因是 :油田内部存在微型小断层、裂缝、稠油环带等复杂地质因素。

Mitoxantrone Ethylcellulose Microspheres for Liver Arte-rial Embolization

Herein,the orthogonal test was used to optimize the preparation conditions and technique of mitoxantrone ethylcellulose microsphere fDHAQ-EC-MS)for liver arterial embolization.The dynamic dialysis method was used to study the drug release characteristics ofthe DRAQ-EC-MS.The suspension of DHAQ-EC-MS for clinical liver arterial embolization was prepared.The results show that the DHAQ-EC-MS is regular in morphology with a mean diameter of 110.24 ± 38.19μm and 86.5% of them within the range of 40-150μm,The drug loading is 12.5% and the embedding ratio is 55.6%. The release characteristics were in accordance with the single exponential model.The drug release equation is log(Y∞-Y)=-0.116t-1.198 × 10￣(-3)(r=0.9992,t(50)=2.6h).The suspension is ofstable physical and chemical properties and is suitable for clinical use.

Targeting Effect Study of ￣(3) H-Mitoxantrone Nanosphereson Hepatocellular Carcinoma(HCC) Model in Nude Mice

The distribution of ￣(3)H-mitoxantrone polybutyl cyanoacrylate nanospheres(￣(3)H-DHAQ-PBCA-NS)in the viscera,muscle and tumors of human hepatocellular carcinoma (HCC)model in nude mice was studied with liquid scintillation counting techniique. The results showed that the ￣(3)H-DHAQ-PBCA-NS had remarkable liver targeting effect. The content of ￣(3)H-DHAQ-PBCA-NSin liver and heterotopic liver tumor was found to be 71.31±10. 49% of total amount of drug in animal body. It was also found that the content of ￣(3)H-DHAQ-PBCA-NS in liver was higher than that in liver tissue, and the content of ￣(3)H-DHAQ-PBCA-NS in annpit tumor was higher than that in armpit muscle tissue,but had no significant difference;It provides an ideal preparation for the DHAQ admini-stration.

Il34拯救甲硝唑导致的斑马鱼中枢神经系统轴突再生障碍

甲硝唑(metronidazole,MTZ)是临床常用的抗感染药物,同时在科学研究中被用作细胞靶向消融系统的前体药物,具有极高的应用价值。但MTZ会引起一定程度的神经毒性症状,目前临床及科研使用过程中也缺乏规避其毒性的有效手段,这在一定程度上限制了其应用。因此,探究MTZ引起神经症状的具体机制并探讨应对措施将更大程度地发挥MTZ的实用价值。本研究利用斑马鱼(Danio rerio)脊髓损伤再生模型确认了MTZ的神经毒性导致斑马鱼中枢神经系统轴突再生障碍,通过在斑马鱼中枢神经系统中过表达il34消除了MTZ对轴突再生的抑制,并证明了这种抗MTZ神经毒性的促再生作用不是由白细胞介素34(interleukin 34,Il34)趋化的过量巨噬细胞/小胶质细胞所介导。通过转录组测序分析组间差异表达基因的GO富集分析发现,Il34通过促进细胞间的黏附和细胞定位等生物学过程抗MTZ神经毒性从而促进脊髓损伤修复。综上所述,本研究揭示了MTZ神经毒性的可能原因,为消除MTZ毒性提供了一个新的视角。

示踪剂盐酸米托蒽醌在甲状腺癌根治术中的应用

目的研究示踪剂盐酸米托蒽醌在甲状腺癌根治术中对淋巴结染色率、淋巴结示踪率及甲状旁腺误切率的影响。方法选取2022年2月至8月于我院行甲状腺癌根治术的106例患者,随机分为对照组和观察组,每组53例。记录患者淋巴结染色率、示踪持续成功率。比较2组患者淋巴结清除数目、甲状旁腺误切率,及2组患者术前及术后第1天、第3天血钙和甲状旁腺激素(PTH)。结果观察组患者淋巴结染色率为90.1%,示踪持续成功率为100%。2组患者淋巴结清除数目,甲状旁腺误切率,术后第1天、第3天血钙和PTH比较差异均有统计学意义(P<0.05)。结论示踪剂盐酸米托蒽醌具有良好的安全性和淋巴结示踪性,能降低甲状旁腺误切率,值得临床推广应用。

示踪剂联合长型Trocar在腔镜甲状腺癌根治术中的应用效果分析

目的:分析示踪剂联合长型一次性穿刺器(Trocar)在腔镜甲状腺癌根治术中的应用效果。方法:选取2018年1月—2022年12月河西学院附属张掖人民医院收治的低危甲状腺癌患者100例作为研究对象,随机分为观察组与对照组,各50例。两组均采用腔镜甲状腺癌根治术治疗,观察组术中应用示踪剂联合长型Trocar;对照组术中使用普通Trocar,不使用淋巴结示踪剂。比较两组手术相关指标、疼痛程度、并发症发生情况。结果:两组手术时间、术中出血量、住院时间比较,差异无统计学意义(P>0.05);观察组颈部分离面积小于对照组,淋巴结清扫数量、术后72 h引流量少于对照组,差异有统计学意义(P<0.001)。术后48 h,两组疼痛评分比较,差异无统计学意义(P>0.05);术后72 h,两组疼痛评分高于术后48 h,但观察组低于对照组,差异有统计学意义(P<0.001)。观察组并发症发生率低于对照组,差异有统计学意义(P=0.046)。结论:示踪剂联合长型Trocar在腔镜甲状腺癌根治术中的应用效果显著,可减轻创伤,缓解疼痛,降低并发症发生率,值得临床应用。

Study on the anticarcinogenic effect and acutetoxicity of liver-targeting mitoxantrone-nanoparticles

AIM To study the anticarcinogenic effect and acute toxicity of liver targeting mitoxantrone nanospheres. METHODS The anticarcinogenic effect of mitoxantrone polybutylcyanoacrylate nanoparticles (DHAQ PBCA NP) was investigated by using heterotopic and orthotopic transplantation models of human hepatocellular carcinoma (HCC) in nude mice and was compared with mitoxantrone (DHAQ) and doxorubicin (ADR). The acute toxicity of DHAQ PBCA NP lyophilized injection in mice was also studied. RESULTS The tumor inhibition rates of ADR, DHAQ, DHAQ PBCA NP to orthotopically transplanted HCC were 60 07%, 67 49% and 99 44%, respectively, but regard to heterotopically transplanted HCC, these were 80 03%, 86 18% and 92 90%, which were concordant with the results acquired by mitosis counting and proliferating cell nuclear antigen (PCNA). After iv administration to mice with DHAQ PBCA NP, the LD 50 was 16 9*!mg/*!kg ± 3 9*!mg/*!kg , no obvious local irritation was observed and there was no significant damage to the structure of liver cells, and that of the heart, spleen and kidneys. CONCLUSION The effect of DHAQ PBCA NP was significantly higher than that of DHAQ and ADR in the anti orthotopically transplanted HCC and the acute toxicity was relatively low.

Comparison of Mitoxantrone in Combination with Intermediate-dose Cytarabine versus High-dose Cytarabine as Consolidation Therapies for Young Non-APL Acute Myeloid Leukemia Patients with Favorable and Intermediate Cytogenetics

In this study,we compared the efficacy of mitoxantrone in combination with intermediate-dose cytarabine（HAM） with that of high-dose cytarabine alone（Hi DAC） as consolidation regimens in non-acute promyelocytic leukemia（APL） acute myeloid leukemia patients with favorable and intermediate cytogenetics.A total of 62 patients from Shenzhen People＇s Hospital were enrolled in this study.All patients enrolled received standard induction chemotherapy and achieved the first complete remission（CR1）.In these patients,24 received Hi DAC and 38 received HAM as consolidation.The median relapse free survival（RFS） and overall survival（OS） were similar between these two consolidation regimens.Even in subgroup analysis according to risk stratification,the combination regimen conferred no benefit in longterm outcome in patients with favorable or intermediate cytogenetics.However,in patients receiving HAM regimen,the lowest neutrophil count was lower,neutropenic period longer,neutropenic fever rate higher,and more platelet transfusion support was required.HAM group also tended to have higher rate of sepsis than Hi DAC group.According to our results,we suggest that combination treatment with mitoxantrone and intermediate-dose cytarabine has limited value as compared to Hi DAC,even in young non-APL AML patients with favorable and intermediate cytogenetics.

Preparation and functional characterization of tumor-targeted folic acid-chitosan conjugated nanoparticles loaded with mitoxantrone

Folic acid conjugated chitosan was prepared by cross-linking reaction with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride(EDC), and then used as a template to prepare folic acid-chitosan(FA-CS) conjugated nanoparticles and load mitoxantrone nanoparticles(FA-CSNP/MTX). Drug dissolution testing, CCK-8 method, and confocal microscopy were used to detect their controlled-release capability in different situations and the specific uptake by HONE1 cells. The experimental results show that the nanoparticles have uniform size distribution of 48-58 nm. The highest encapsulation rate of the particles on mitoxantrone hydrochloride(MTX) is(77.5±1.9)%, and the drug loading efficiency is(18.4±0.4)%. The sustained release effect, cell growth inhibition activity and targeting effect of the FA-CS/MTX nanoparticles are good in artificial gastric fluid and intestinal fluid. It is demonstrated that the FA-CSNP system is a potentially useful system for the targeted delivery of anticancer drug MTX.

Sensitive Voltammetric Determination of Mitoxantrone by Using CS-Dispersed Graphene Modified Glassy Carbon Electrodes

A novel CS-dispersed graphene modified glassy carbon electrode was fabricated. Study electrochemical characteristics of mitoxantrone in the CS-dispersed graphene modified electrode by cyclic voltammetry and other methods, by selecting and optimizing the various parameters to create a new electrochemical method for the determination of mitoxantrone. The linear range of the oxidation peak current is from 6×10–10 to 1 ×10–6 mol/l in this method, after 2.5 mins open-circuit accumulation, the limit of detection is 2×10–10 mol/l. After 10 parallel determinations, the relative standard deviation was 3.7% that the concentration of mitoxantrone was 1×10–8 mol/l. The modified electrode has been successfully applied for the assay of mitoxantrone in human urine samples.

复方MTZ海绵制剂治疗下颌智齿冠周炎疗效观察

目的对比评价复方MTZ海绵制剂与常规治疗下颌智齿冠周炎的临床疗效。方法随机选择门诊226例下颌智齿冠周炎患者,分为2组,治疗组112例在智齿龈袋内置入复方MTZ海绵制剂。对照组114例置入碘甘油。结果2组总有效率分别为95.54%和77.19%,差异有显著性(P<O.01)。结论复方MTZ海绵制剂治疗智齿冠周炎临床疗效优于碘甘油。

Electrochemical Behavior of Mitoxantrone and Its Determination at a Pt/C Implanted Modified Microelectrode

In a 0.02 mol/L Na_2HPO_4-KH_2PO_4(PBS) buffer solution(pH=6.82), the electrochemical behavior of mitoxantrone was studied by linear-sweep voltammetry and cyclic voltammetry at a Pt/C ion implantation modified microelectrode. A sensitive reduction peak was observed. The peak potential was \{-0.72 V\}(vs.SCE), the peak current was proportional to the concentration of mitoxantrone within the ranges of 7.0×10 -8—9.0×10 -7 mol/L and 1.0×10 -6—2.4×10 -5 mol/L, with a detection limit of 4.0×10 -8 mol/L. The linear correlation coefficients were 0.9994 and 0.9992, respectively. This method has been applied to the direct determination of mitoxantrone in simulated urine. The recoveries were in the range from 96.2% to 105.9%. The reduction process was a quasi-reversible one with adsorptive characteristics at the Pt/C microelectrode. The electrode reaction rate constant k_s and the electron transfer coefficient α of the system were determined to be 4.5 and 0.65 s -1, respectively. The experiments showed that Pt element had surely been implanted into the surface of the carbon fiber, and the atomic Pt improved the electrocatalytic activity. The Pt/C microelectrode had a good stability and reproducibility.

Destroying MTZ black holes with test particles

Neglecting the self-force and radiative effects, we follow the spirit of Wald＇s gedanken experiment and discuss whether a （2＋1）-dimensional Martinez-Teitelboim-Zanelli （MTZ） black hole can turn into a naked singularity by cap- turing a charged and massive particle. We find that after capturing a charged and massive test particle, an extremal or near-extremal MTZ black hole could turn into naked singularity, leading to a possible violation of the cosmic censorship. There exist ranges of the test particles＇ energies ＆E which allow the appearance of naked singularities from both extremal and near extremal MTZ black holes.

Interaction Between Mitoxantrone Metal Complex and Titan Yellow by Resonance Rayleigh Scattering Spectra and Its Analytical Application

In a pH 2.4 Britton-Robinson buffer medium, the anthracycline antibiotics mitoxantrone（MXT） could react with metal ions such as Pd（Ⅱ）, Co（Ⅱ） and Cu（Ⅱ） to form 1：2（molar ratio） cationic chelates, which further reacted with the anionic dye titan yellow to form 1：2 ternary ion-association complexes by electrostatic interaction. As a result, the intensity of resonance Rayleigh scattering（RRS） was enhanced greatly. These RRS spectral characteristics of various metal ion systems were similar, and the maximum RRS wavelengths were all located at 454 nm. But the increments of RRS intensities were different in the series of Pd（Ⅱ）〉Co（Ⅱ）〉Cu（Ⅱ）. The enhanced RRS intensities were proportional to the concentration of MXT in a range of 0.03-2.4μg/mL and the detection limit（3σ） was 0.009μg/mL for the Pd（Ⅱ） system. In this study, the optimum conditions of the reactions and the effects of foreign substances were investigated, in addition, the composition and reaction mechanism of ion-association complexes were discussed. Thus a highly sensitive, simple and rapid method is proposed for the determination of MXT in urine and serum samples.