Treatment of thalassaemia: a review of the new approaches on transfusion safety and the novel therapeutics

Lifetime red cell concentrate (RCC) transfusions still account for significant iron overload‐related morbidity and mortality despite chelation therapy in thalassaemia. The cumulative risk of transfusion‐transmitted infections is substantial for thalassaemia patients. Pathogen reduction technologies for RCC may imply a proactive approach against new/re‐emerging pathogens and may be an ultimate safeguard for transfusion safety in the developing countries. Red cell alloimmunization may become a significant clinical challenge in thalassaemia. The availability of high‐throughput molecular blood group antigen typing in the donors may allow perfect match transfusion, beyond ABO‐D and CEK antigen‐matched transfusions. Allogeneic stem cell transplantation (A‐SCT) is the only available curative therapy in thalassaemia, but carries a substantial risk of serious adverse events and mortality. Gene addition therapy for correction of the α‐globin chain imbalance overcomes the problems of donor availability and immunological complications of A‐SCT. Gene editing by either gene disruption or correction emerged as a potential alternative to gene addition therapy in beta‐thalassaemia. A new era of novel therapeutics targeting α/β imbalance, ineffective erythropoiesis or iron dysregulation is unfolding in thalassaemia management, and a number of those now have agents in preclinical and clinical development. Hydroxyurea (HU) may improve globin chain imbalance and be beneficial for reducing or omitting transfusion requirement. Ruxolitinib has allowed steady decrease in spleen volume that may serve for avoiding splenectomy in beta‐thalassaemia. Luspatercept may restore normal erythroid differentiation and improve anaemia. Hepcidin mimetics or TMPRSS6 inhibitors may modulate ineffective erythropoiesis by iron restriction and improve anaemia and organ iron loading.     

补骨脂素抗增生性瘢痕作用机制研究

目的探讨补骨脂素抗增生性瘢痕的作用机制。方法体外培养成纤维细胞,按随机数字表法分为正常组(培养正常成纤维细胞)、瘢痕组(培养增生性瘢痕成纤维细胞)、TGF-β1组(10 ng/ml TGF-β1处理增生性瘢痕成纤维细胞5 min^12 h)、Smurf2 RNA干扰组[Smad泛素化调节因子2(Smad ubiquitin regulatory factor2,Smurf2)siRNA转染增生性瘢痕成纤维细胞72 h]、补骨脂素组(10μmol/L补骨脂素处理增生性瘢痕成纤维细胞继续培养72 h)、补骨脂素+TGF-β1组(增生性瘢痕成纤维细胞加入补骨脂素培养72 h后加入TGF-β1培养6 h)。采用Western blot法检测Smurf2、α-平滑肌肌动蛋白(α-actin SMA,α-SMA)蛋白表达;RT-PCR法检测Ⅰ型胶原蛋白mRNA表达;ELISA法检测TGF-β1蛋白分泌。结果与正常组比较,瘢痕组Smurf2蛋白[(0.83±0.08)比(0.38±0.07)]表达增加(P<0.05);与瘢痕组比较,Smurf2 RNA干扰组TGF-β1[(2.2±0.18)比(4.2±0.47)]表达降低(P<0.05);TGF-β1组Smurf2[(0.71±0.06)比(0.42±0.04)]、α-SMA[(1.42±0.12)比(0.91±0.09)]蛋白表达增加(P<0.05),Ⅰ型胶原蛋白mRNA[(0.72±0.09)比(0.41±0.07)]表达增加(P<0.05);补骨脂素组Smurf2[(0.05±0.01)比(0.42±0.04)]、α-SMA[(0.71±0.07)比(0.91±0.09)]蛋白表达降低(P<0.05),Ⅰ型胶原蛋白mRNA表达[(0.12±0.04)比(0.41±0.07)]降低(P<0.05)。结论补骨脂素可能通过TGF-β1/Smurf2信号通路抑制α-SMA蛋白表达,从而降低Ⅰ型胶原蛋白表达,起到抑制瘢痕形成的作用。     

腮腺显像对鼻咽癌放疗后腮腺功能的评价

目的利用腮腺显像研究鼻咽癌放疗后腮腺的摄取与排泄功能.方法48例鼻咽癌患者中,对38例肿瘤和肿大淋巴结行加速调强放疗（SMART）,其亚临床灶和预防照射区接受常规照射;余10例行常规放疗.放疗前后均行腮腺显像,计算腮腺的放射性摄取指数（UI）及酸性刺激后排泌指数（EI）,对腮腺功能损伤情况进行分析;同时记录患者口干程度并分级.结果鼻咽癌SMART组放疗后腮腺UI和EI分别下降21.9%和37.3%,中重度口干者12例;而常规放疗组腮腺功能明显下降,UI和EI分别下降56.1%和96.1%,中重度口干者9例,两者比较差异均有显著性（P＜0.05）.结论腮腺显像可灵敏地监测鼻咽癌放疗后腮腺功能.     

放射性碘对大鼠致癌效应的研究

对雄性Wisiaf大鼠腹腔1次注射碘-13l, 注入活度分别为0.59×10⁴Bq,2.37×10⁴Bq, 4.34×10⁴Bq, 8.23×10⁴Bq, 碘-125注入活度分别为3.7×10⁴Bq, 7.4×10⁴Bq, 14.8×10⁴Bq, 22.2×10⁴Bq.碘-131诱发肿痛实际注入活度在2.37×10⁴Bq以下,碘-125的为7.4×10⁴以下.诱发的肿瘤以甲状腺肿瘤为主,其次为垂体肿瘤.     

经肝动脉灌注^131 I-HAblSF（ab’）2治疗肝癌合并门静脉癌栓疗效分析

目的探讨经肝动脉灌注^131 I-HAbl8F（ab’）2治疗肝癌合并门脉癌栓的价值。方法8例合并门脉癌栓的晚期肝癌患者行经肝动脉超选择灌注^131 I-HAbl8F（ab＇）2临床治疗性试验，剂量：0．75mCi／kg。分析症状、卡氏评分、肝功能、AFP及肿瘤CT等影像变化，随访近期疗效。结果7例疼痛患者中，3例症状缓解。3例卡氏评分增加、4例稳定。6例AFP异常患者治疗后3例下降。全组病例用药后肝功能损害均无明显加重。1例无明显症状的弥漫型肝癌患者治疗后病灶减少；余7例中，瘤体增大5例、缩小2例，其中，PR2例，临床有效率28．6％。本组1例1年随访时生存。结论经肝动脉灌注0．75mCi／kg ^131 I-HAbl8F（ab＇）2对合并门脉癌栓的肝癌患者肝功影响小，对门脉分支癌栓患者有较好的疗效。     

18F-FDG hPET/CT显像诊断结直肠癌术后复发转移

目的 评价^18F-FDG hPET／CT代谢显像对结直肠癌患者术后复发转移的诊断价值。方法 对81例结直肠癌术后临床可疑肿瘤复发或转移的患者采用GEHAWKEYE符合线路SPECT进行^18F-FDG显像，获得经X线衰减校正后的三维断层图像，由计算机完成各断层图像的融合，以目测法进行诊断分析，并与CT、病理学检查、临床随访作出的最后诊断进行对比。结果 ^18F-FDG hPET／CT代谢显像对结直肠癌术后复发、转移诊断的灵敏度为93％（57／61），特异性为80％（16／20），阳性预测率为93％（57／61），阴性预测率为80％（16／20）；而常规CT对结直肠癌术后复发转移诊断的灵敏度、特异性、阳性预测值、阴性预测值分别为67％（37／55）、73％（19／26）、84％（37／44）、51％（19／37）；^18F-FDG hPET／CT代谢显像共检出病灶126个，65例相同视野hPET／CT代谢显像与诊断CT常规影像检查复发转移病灶检出数分别为91个和46个。结论 ^18F-FDG hPET／CT显像对结直肠癌术后复发转移的诊断价值优于CT；通过与同机定位CT图像融合可有效地对病变进行定性定位。     

National intercomparisons of I radioactivity measurements in nuclear medicine centres in India

National intercomparisons of activity measurements of ¹³¹I, a radioisotope widely used for diagnosis and therapy of thyroid related ailments, were initiated in 1979 as a quality assurance program, towards improving radiation safety procedures and related dosimetry in Nuclear Medicine Centres (NMCs) in India. Oral administration of a known quantity of radioiodine to patients requires accurate radioactivity measurements to be performed on a well-calibrated isotope calibrators. Under or over estimation of the activity due to a faulty or uncalibrated isotope calibrator could provide misleading results. Calibration of isotope calibrators and the traceablity of subsequent measurements to the national standards laboratory is one of the essential basic radiation safety requirement of the IAEA. In view of the stringent quality assurance requirements for activity measurements imposed by Atomic Energy Regulatory Board, a National Intercomparison Program was initiated and to date ten such intercomparison programs have been conducted by the Radiation Safety Systems Division, of the Bhabha Atomic Research Centre. This program has benefited the participants by making their measurements traceable to the National Primary Standards. Over the years there has been a marked increase in the number of NMCs participating in the intercomparison programs. As a result, the number of institution showing large deviation from the correct value has decreased considerably over the years. This program thus, has enabled participating NMCs to check their isotope calibrators so as to ensure proper delivery of radiation dose to the patients and hence to optimise patient exposure.     

质子磁共振波谱在胶质瘤诊断中的应用

目的探讨质子磁共振波谱（^1Hmagnetic resonance spectroscopy，^1HMRS）在胶质瘤诊断及分级中的应用。方法回顾分析我院2003年3月～2005年9月质子磁共振波谱检查并经病理证实的36例胶质瘤的临床资料，根据胶质瘤恶性程度不同分为A、B2组，其中A组为低恶性组（包括星形细胞瘤Ⅰ级和Ⅱ级、室管膜瘤、少突胶质细胞瘤等）21例，B组为高恶性组（包括星形细胞瘤Ⅲ级和Ⅳ级、多形性胶质母细胞瘤、间变型室管膜瘤、髓母细胞瘤）15例。观察氮乙酰门冬氨酸（Nacetylaspartate，NAA）、胆碱（choline，Cho）、肌酸（creatine，Cr）、肌醇（Ins）的共振峰及比值。大脑对侧对应正常脑组织的结果作内对照组。结果2组胶质瘤均表现为异常的。HMRS，与大脑对侧对应正常脑组织相比，A、B2组表现为NAA／Cr含量显著下降，Cho／Cr含量显著增高（P均〈0．05），cr总量变化不大，且无规律性（P〉0．05），Ins含量表现为轻度下降（P〉0．05）。A组NAA／Cr和NAA／Cho均显著高于B组（t=4．235，P=0．011；t=2．832，P=0．031），A组Cho／Cr显著低于B组（t=-2．323，P=0．042）。结论。HMRs可提高对胶质瘤诊断和分级的准确性。     

应用3H-TdR掺入法对SMMC-7721细胞株药敏试验条件的探讨与应用

目的探讨3H-TdR掺入法在进行SMMC-7721系细胞肿瘤药敏试验实验时的最佳实验条件.方法确定出3H-TdR掺入法药敏实验时的最适细胞浓度、最适实验药物浓度、3H-TdR掺入最适时间;在最适条件下采用3H-TdR掺入法测定肝癌SMMC-7721细胞株对临床常用的9种抗癌药物的敏感性.结果应用3H-TdR掺入法检测肝癌SMMC-7721细胞株药敏试验的最适实验细胞浓度为1×104个/孔,最适试验药物浓度为1×PPC,3H-TdR最适掺入时间为收集细胞前8 h;肝癌SMMC-7721细胞株对DDP、ADM、5-FU、CPT高度敏感,对MTX、VP-16、MMC、NVB低度敏感,对PYM不敏感.结论 3H-TdR掺入法可用于肿瘤药物敏感性测定并确定出它的最适实验条件.     

用金标法快速测定血清中cTn-Ⅰ在急性心肌梗死诊断上的应用

为探讨急性心肌梗死和疑为心梗病人血中 c Tn I的敏感性和特异性 ,采用金标法对 5 2例就诊病人测定其血中 c Tn- 和酶学法测定 CK- MB两个指标 ,结果发现急性心肌梗死组病人血中的 c Tn- 敏感度高于 CK- MB,但二者无显著性差异 ;而疑为心梗病人血中的 c Tn- 敏感度高于 CK- MB且具有显著的特异性。c Tn- 的测定对急性心肌梗死病人的诊断和治疗具有特别重要的意义