脂肪干细胞治疗下肢缺血的研究进展

下肢缺血性疾病是临床常见的严重危害中老年人健康的疾病之一。目前，临床针对下肢缺血性疾病的治疗方法多样，但远 期疗效欠佳，对于肢体严重缺血的患者往往需要进行截肢处理。脂肪干细胞（adipose-derived stemcells, ADSCs）作为再生医学用 于治疗下肢缺血的种子细胞具有广阔的应用前景。本文将对ADSCs 治疗下肢缺血的研究进展进行综述。     

Synthesis and biological evaluation of glucose conjugated phthalocyanine as a second-generation photosensitizer

Photodynamic therapy (PDT) is a treatment method using light and photosensitizers (PSs), which is categorized as a non-invasive surgery treatment for cancers. When the tumor is exposed to a specific light, the PSs become active and generate reactive oxygen species (ROS), mainly singlet oxygen which kills nearby cancer cells. PDT is becoming more widely recognized as a valuable treatment option for localized cancers and pre-cancers of skin as it has no long-term effects on the patient. But, due to the limited penetration rate of light into the skin and other organs, PDT can’t be used to treat large cancer cells or cancer cells that have grown deeply into the skin or other organs. Hence, in this study, our focus centers on synthesizing glucose-conjugated phthalocyanine (Pc) compatible with near-infrared (NIR) irradiation as second-generation photosensitizer, so that PDT can be used in a wider range to treat cancers without obstacles.     

饮食疗法对妊娠期糖尿病孕妇血脂代谢动态变化的研究

目的:探讨脂代谢紊乱在妊娠期糖尿病(GDM)中的作用,为妊娠期糖尿病的预防及指导临床干预提供理论依据。方法:观察妊娠期糖尿病患者和糖耐量正常孕妇血脂水平及胰岛素抵抗程度差异,分析妊娠期糖尿病患者饮食治疗前后的血脂及炎症标志物的动态变化,于孕12W、24W及36W分别抽取两组孕妇空腹静脉血,测定糖、脂代谢指标及炎症标志物水平,计算血浆致动脉粥样硬化指数(atherogenic index of the plasma,AIP);应用稳态模型胰岛素抵抗指数(HOMA-IR)及胰岛分泌功能指数(HBCI),评价胰岛素抵抗指数(IR)程度及胰岛功能。结果:(1)GDM组的C肽、FINS、HOMA-IR明显高于糖耐量正常组(normal glucose tolerance,NGT)组(p0.05),GDM组HBCI指数低于NGT组(p0.05)。(2)干预组与对照组比较,12W时,TC、TG、HDL、LDL差异均无统计学意义(p0.05);24W及32W差异均有统计学意义(p0.05),均较对照组高。(3)对GDM组中TC、TG、HDL、LDL、AIP、hs-CRP、N及WBC值进行分析,TG、TC、LDL、AIP、hs-CRP、N及WBC值24W较36W及12W高(p0.05);HDL水平24W较36W及12W低(p0.05)。(4)NGT组中TG、TC、LDL、AIP、hs-CRP、N及WBC值36W较24W及12W高(p0.05);HDL水平36W较24W及12W高(p0.05)。结论:GDM孕妇存在着明显的胰岛素抵抗和胰岛β细胞分泌功能受损。GDM孕妇合并较正常妊娠更为严重的炎症反应,血脂水平明显升高,饮食治疗后对改善IR有益,提示在妊娠期糖尿病患者中,通过适当的饮食治疗进而对血糖及血脂的调整可以显著减少母儿并发症。     

急性早幼粒细胞白血病巩固治疗现状及进展

急性早幼粒细胞白血病(APL)曾被认为是最迅速的致命白血病,特点为临床表现凶险,早期死亡率高,治愈率低。药物全反式维甲酸及亚砷酸的应用,使APL的治疗取得了很大成功,其完全缓解率可达90%。然而APL的复发率仍然较高,约15%-30%。降低复发率和提高长期生存已成为研究重点,如何选择合理的缓解后治疗策略至关重要。缓解后治疗一般包括巩固治疗和维持治疗,而最佳治疗方案的确定仍然有待商榷。因此,本文就APL缓解后巩固治疗回顾相关文献进行整合分析,综述APL巩固治疗的研究进展。     

Bacterial xenophagy and its possible role in cancer: A potential antimicrobial strategy for cancer prevention and treatment

Macroautophagy/autophagy is a conserved catabolic process through which cellular excessive or dysfunctional proteins and organelles are transported to the lysosome for terminal degradation and recycling. Over the past few years increasing evidence has suggested that autophagy is not only a simple metabolite recycling mechanism, but also plays a critical role in the removal of intracellular pathogens such as bacteria and viruses. When autophagy engulfs intracellular pathogens, the pathway is called ‘xenophagy’ because it leads to the elimination of foreign microbes. Recent studies support the idea that xenophagy can be modulated by bacterial infection. Meanwhile, convincing evidence indicates that xenophagy may be involved in malignant transformation and cancer therapy. Xenophagy can suppress tumorigenesis, particularly during the early stages of tumor initiation. However, in established tumors, xenophagy may also function as a prosurvival pathway in response to microenvironment stresses including bacterial infection. Therefore, bacterial infection-related xenophagy may have an effect on tumor initiation and cancer treatment. However, the role and machinery of bacterial infection-related xenophagy in cancer remain elusive. Here we will discuss recent developments in our understanding of xenophagic mechanisms targeting bacteria, and how they contribute to tumor initiation and anticancer therapy. A better understanding of the role of xenophagy in bacterial infection and cancer will hopefully provide insight into the design of novel and effective therapies for cancer prevention and treatment.     

Quantitative comparison between the commercial software STRATOS® by Philips and a homemade software for voxel-dosimetry in radiopeptide therapy

BackgroundTargeted radionuclide therapy is a rapidly growing modality. A few commercial treatment planning systems are entering the market. However, some in-house systems are currently developed for a more flexible and customized dosimetry calculation at voxel-level. For this purpose, we developed a novel software, VoxelMed, and performed a comparison with the software STRATOS.MethodsThe validation of both of them was undertaken using radioactive phantoms with different volume inserts. A cohort of 10 patients was also studied after a therapeutic administration of ¹⁷⁷Lu-labelled radiopeptides. The activity, number of disintegrations, absorbed dose and dose-volume histogram (DVH) were calculated for the phantoms and the kidneys in patients, which were the main critical organs at risk in this study.ResultsIn phantoms the absorbed doses computed with VoxelMed and STRATOS agree within 5%. In patients at the voxel-level the absorbed dose to kidneys (VoxelMed: mean 0.66 Gy/GBq) showed a limited difference of 5%, but with a remarkable range (−40%, +60%) between the two software packages. Voxel-dosimetry allows to estimate the dose non-homogeneities in volumes, which may be evaluated through DVHs.ConclusionThis study demonstrates that a fully 3D voxel-dosimetry with multiple SPECT images is feasible by using home-made or commercial software package and absorbed dose results obtained are similar. The main difference between the studied tools was observed in the activity integration method (effective vs physical half-time to time activity curve tail). We believe that an effective half-time integration method produces a more accurate approximation of clinical uptake and resultant dosimetry.     

Combination of dual-energy computed tomography and iterative metal artefact reduction to increase general quality of imaging for radiotherapy patients with high dense materials. Phantom study

PurposeTo evaluate the use of pseudo-monoenergetic reconstructions (PMR) from dual-energy computed tomography, combined with the iterative metal artefact reduction (iMAR) method.MethodsPseudo-monoenergetic CT images were obtained using the dual-energy mode on the Siemens Somatom Definition AS scanner. A range of PMR combinations (70–130 keV) were used with and without iMAR. A Virtual Water™ phantom was used for quantitative assessment of error in the presence of high density materials: titanium, alloys 330 and 600. The absolute values of CT number differences (AD) and normalised standard deviations (NSD) were calculated for different phantom positions. Image quality was assessed using an anthropomorphic pelvic phantom with an embedded hip prosthesis. Image quality was scored blindly by five observers.ResultsAD and NSD values revealed differences in CT number errors between tested sets. AD and NSD were reduced in the vicinity of metal for images with iMAR (p < 0.001 for AD/NSD). For ROIs away from metal, with and without iMAR, 70 keV PMR and pCT AD values were lower than for the other reconstructions (p = 0.039). Similarly, iMAR NSD values measured away from metal were lower for 130 keV and 70 keV PMR (p = 0.002). Image quality scores were higher for 70 keV and 130 keV PMR with iMAR (p = 0.034).ConclusionThe use of 70 keV PMR with iMAR allows for significant metal artefact reduction and low CT number errors observed in the vicinity of dense materials. It is therefore an attractive alternative to high keV imaging when imaging patients with metallic implants, especially in the context of radiotherapy planning.     

Evaluation of residual abdominal tumour motion in carbon ion gated treatments through respiratory motion modelling

At the Italian National Centre for Oncologic Hadrontherapy (CNAO) patients with upper-abdominal tumours are being treated with carbon ion therapy, adopting the respiratory gating technique in combination with layered rescanning and abdominal compression to mitigate organ motion. Since online imaging of the irradiated volume is not feasible, this study proposes a modelling approach for the estimation of residual motion of the target within the gating window. The model extracts a priori respiratory motion information from the planning 4DCT using deformable image registration (DIR), then combines such information with the external surrogate signal recorded during dose delivery. This provides estimation of a CT volume corresponding to any given respiratory phase measured during treatment. The method was applied for the retrospective estimation of tumour residual motion during irradiation, considering 16 patients treated at CNAO with the respiratory gating protocol. The estimated tumour displacement, calculated with respect to the reference end-exhale position, was always limited (average displacement is 0.32 ± 0.65 mm over all patients) and below the maximum motion defined in the treatment plan. This supports the hypothesis of target position reproducibility, which is the crucial assumption in the gating approach. We also demonstrated the use of the model as a simulation tool to establish a patient-specific relationship between residual motion and the width of the gating window. In conclusion, the implemented method yields an estimation of the repeatability of the internal anatomy configuration during gated treatments, which can be used for further studies concerning the dosimetric impact of the estimated residual organ motion.     

Eradication of melanoma in vitro and in vivo via targeting with a Killer-Red-containing telomerase-dependent adenovirus

Melanoma is a highly recalcitrant cancer and transformative therapy is necessary for the cure of this disease. We recently developed a telomerase-dependent adenovirus containing the fluorescent protein Killer-Red. In the present report, we first determined the efficacy of Killer-Red adenovirus combined with laser irradiation on human melanoma cell lines in vitro. Cell viability of human melanoma cells was reduced in a dose-dependent and irradiation-time-dependent manner. We used an intradermal xenografted melanoma model in nude mice to determine efficacy of the Killer-Red adenovirus. Intratumoral injection of Killer-Red adenovirus, combined with laser irradiation, eradicated the melanoma indicating the potential of a new paradigm of cancer therapy.