Local Recurrence of Soft Tissue Sarcoma Revisited: Is there a Role for “Selective” Radiation?

BackgroundRadiation therapy (RT) is often utilized in cases of high-grade soft tissue sarcoma (STS), but there remain situations where treatment is with surgical excision alone. Our goals were to determine (1) the local recurrence (LR) rate with and without perioperative RT and (2) associations between local recurrence, patient, tumor, and treatment variables.MethodsWe performed a retrospective review of 165 consecutive STS patients. A Cox proportional hazards model was used to investigate variables associated with local recurrence.ResultsLR occurred in 15/78 (19%) without RT, 4/29 (14%) with postoperative RT, and 0/58 with preoperative RT (p=0.002). We found increased rates of local recurrence at 24 months for myxofibrosarcoma (p=0.001) and no-RT (p=0.003). Myxofibrosarcoma accounted for 33 (20%) of the study patients and 12 (63%) of the local recurrences.ConclusionThe LR rate in patients treated with surgery alone was disproportionately attributable to myxofibrosarcoma (11/23 cases, 48%). Other subtypes demonstrated a lower rate of LR in the absence of RT (4/55 cases, 7%), and no LR occurred when final margins were >2 mm. In certain circumstances treatment with a negative margin surgical resection followed by close observation is justifiable. RT is effective and should continue to be considered routinely in myxofibrosarcoma or when surgical margins are inadequate. Level of Evidence: III     

Two combined photosensitizers: a goal for more effective photodynamic therapy of cancer

Photodynamic therapy (PDT) is a clinically approved therapeutic modality for the treatment of diseases characterized by uncontrolled cell proliferation, mainly cancer. It involves the selective uptake of a photosensitizer (PS) by neoplastic tissue, which is able to produce reactive oxygen species upon irradiation with light, leading to tumor regression. Here a synergistic cell photoinactivation is reported based on the simultaneous administration of two PSs, zinc(II)-phthalocyanine (ZnPc) and the cationic porphyrin meso-tetrakis(4-N-methylpyridyl)porphine (TMPyP) in three cell lines (HeLa, HaCaT and MCF-7), using very low doses of PDT. We detected changes from predominant apoptosis (without cell detachment) to predominant necrosis, depending on the light dose used (2.4 and 3.6 J/cm², respectively). Analysis of changes in cytoskeleton components (microtubules and F-actin), FAK protein, as well as time-lapse video microscopy evidenced that HeLa cells were induced to undergo apoptosis, without losing adhesion to the substrate. Moreover, 24 h after intravenous injection into tumor-bearing mice, ZnPc and TMPyP were preferentially accumulated in the tumor area. PDT with combined treatment produced significant retardation of tumor growth. We believe that this combined and highly efficient strategy (two PSs) may provide synergistic curative rates regarding conventional photodynamic treatments (with one PS alone).     

血府逐瘀汤联合四联疗法治疗Hp阳性慢性萎缩性胃炎的临床观察

目的:探究血府逐瘀汤联合四联疗法治疗幽门螺旋杆菌(Hp)阳性慢性萎缩性胃炎的效果。方法:回顾性分析2014年5月-2017年12月在我院进行诊治的80例Hp阳性慢性萎缩性胃炎患者的临床资料,按照其入院顺序经随机数字表分为研究组和对照组,每组各40例患者。其中,对照组患者采用四联疗法,研究组患者在对照组基础上联合血府逐瘀汤进行治疗,对比两组患者的Hp转阴率、治疗前后胃黏膜病理积分的变化情况、临床症状积分的变化情况和不良反应发生率。结果:治疗后,研究组患者的Hp转阴率[85.0%(34/40)]显著高于对照组[62.5%(25/40)](P0.05)。两组上腹痛、纳差、上腹胀、反酸、嗳气等临床症状积分以及胃黏膜萎缩、肠化、不典型增生等病理积分均显著低于治疗前(P0.05),且研究组以上指标均明显低于对照组(P0.05)。研究组患者的不良反应发生率[5.0%(2/40)]与对照组[12.5%(5/40)]无显著性差异(P0.05)。结论:血府逐瘀汤联合四联疗法治疗Hp阳性慢性萎缩性胃炎的效果显著优于单用四联疗法,其可有效改善患者的病变程度和临床症状,且无明显不良反应产生。     

Evaluation of human pancreatic RNase as effector molecule in a therapeutic antibody platform

Human antibody-ribonuclease (RNase) fusion proteins, referred to as immunoRNases, have been proposed as an alternative to heterologous immunotoxins, without their immunogenicity and unspecific toxicity issues. In this study, we investigated if human pancreatic RNase will be suitable as effector component in a therapeutic antibody development platform. We generated several fusion proteins consisting of tumor-specific human immunoglobulins (IgGs) and human pancreatic RNase. Transient mammalian cell production was efficient and IgG-RNases were purified to homogeneity. Antigen binding was comparable to the parental antibodies and RNase catalytic activity was retained even in the presence of 50-fold molar excess of human cytosolic RNase inhibitor (RI). Serum stability, cell binding and internalization of IgG-RNases were comparable to the parental IgGs. Despite these promising properties, none of the IgG-RNases revealed significant inhibition of tumor cell growth in vitro even when targeting different antigens putatively employing different endocytotic pathways. The introduction of different linkers containing endosomal protease cleavage sites into the IgG-RNase did not enhance cytotoxicity. Similarly, RI evasive human pancreatic RNase variants mediated only small inhibiting effects on tumor cell growth at high concentrations, potentially reflecting inefficient cytosolic translocation. Taken together, human pancreatic RNase and variants did not prove to be generally suitable as effector component for a therapeutic antibody drug development platform.     

静脉溶栓时机对急性ST段抬高型心肌梗死患者溶栓效果及主要不良心脏事件发生率的影响

目的:探讨静脉溶栓时机对急性ST段抬高型心肌梗死患者溶栓效果及主要不良心脏事件发生率的影响。方法:将2016年1月至2017年12月我院接诊的314例急性ST段抬高型心肌梗死患者纳入本研究,按照溶栓治疗时间不同分为A组(发病至溶栓时间6 h)172例、B组(发病至溶栓时间为6～12 h)102例和C组(发病至溶栓时间12 h)40例,比较三组患者溶栓效果、溶栓后ST段回落情况以及住院期间主要不良心脏事件发生情况。结果:A组患者梗死冠脉溶通率、溶栓后ST段回落幅度高于B组和C组,且B组高于C组,差异均有统计学意义(P0.05)。A组患者治疗后ST段回落最大幅度所需时间、住院期间主要不良心脏事件总发生率低于B组和C组,且B组低于C组,差异均有统计学意义(P0.05)。结论:急性ST段抬高型心肌梗死患者发病后6 h内静脉溶栓治疗梗死冠脉溶通率更高、ST段回落效果更好,可降低住院期间主要不良心脏事件发生风险。     

不同CRRT治疗时机对脓毒症合并急性肾功能不全患者疗效及预后的影响

目的:探讨不同持续性肾脏替代治疗(CRRT)治疗时机对脓毒症合并急性肾功能不全患者的临床疗效及预后的影响。方法:将我院ICU收治的60例脓毒症合并急性肾功能不全患者,按照CRRT治疗时机分为早期组(1-2期,n=30)和晚期组(3期,n=30)。比较两组患者治疗前后不同时点平均动脉压(MAP)、白细胞(WBC)计数、血红蛋白(HB)、血小板(PLT)计数、急性生理学与慢性健康状况(APACHE)Ⅱ评分等临床资料的变化,机械通气时间,肾功能恢复率及28 d病死率等。结果:与早期组比较,晚期组治疗后WBC计数明显升高(P0.05)。治疗后12 h、24 h、72 h,早期组ACHEⅡ评分较晚期组显著降低(P0.05)。与晚期组比较,早期组机械通气时间显著缩短,肾功能恢复明显升高,28d内病死率也明显降低(P0.05)。结论:脓毒症合并急性肾功能不全患者应早期启动CRRT治疗,最佳介入时间是KDIGO-AKI 3期之前,有助于改善患者预后。     

The PPARγ ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells

The androgen receptor (AR) regulates growth and progression of androgen-dependent as well as androgen-independent prostate cancer cells. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have been reported to reduce AR activation in androgen-dependent LNCaP prostate cancer cells. To determine whether PPARγ ligands are equally effective at inhibiting AR activity in androgen-independent prostate cancer, we examined the effect of the PPARγ ligands ciglitazone and rosiglitazone on C4-2 cells, an androgen- independent derivative of the LNCaP cell line. Luciferase-based reporter assays and Western blot analysis demonstrated that PPARγ ligand reduced dihydrotestosterone (DHT)-induced increases in AR activity in LNCaP cells. However, in C4-2 cells, these compounds increased DHT-induced AR driven luciferase activity. In addition, ciglitazone did not significantly alter DHT-mediated increases in prostate specific antigen (PSA) protein or mRNA levels within C4-2 cells. siRNA-based experiments demonstrated that the ciglitazone-induced regulation of AR activity observed in C4-2 cells was dependent on the presence of PPARγ. Furthermore, overexpression of the AR corepressor cyclin D1 inhibited the ability of ciglitazone to induce AR luciferase activity in C4-2 cells. Thus, our data suggest that both PPARγ and cyclin D1 levels influence the ability of ciglitazone to differentially regulate AR signaling in androgen-independent C4-2 prostate cancer cells.     

先天性心脏病"双期三步法"筛查诊断流程推广应用初探

摘要 目的：分析"双期三步法"筛查诊断流程在西安咸阳地区新生儿先天性心脏病筛查中的推广与应用价值。方法：选取2021年1月1日-2021年12月31日在医院产检的胎儿和出生的新生儿作为研究对象，收集胎儿期、新生儿期和婴儿期的先心筛查数据，将新生儿分为杂音组、经皮氧饱和度阳性组、双阳性组，评价"双期三步法"筛查方法的使用价值。结果：共对12318例新生儿进行了筛查，筛查阳性497例。确诊126例，实际发病率为10.23‰。在确诊的例先心病患儿中，位于前3位的疾病类型分别为房间隔缺损66例（52.38%），室间隔缺损41例（32.54%），动脉导管未闭11例（8.73%）。杂音组184例，单纯心脏杂音筛查检出率1.49%，灵敏度为82.5%，特异度为99.3%。经皮氧饱和度阳性组147例，单纯经皮氧饱和度阳性筛查检出率1.19%，灵敏度为58.7%，特异度为99.4%。双阳性组166例，两项指标联合筛查检出率1.35%，灵敏度为94.4%，特异度为99.6%。结论："双期三步法"筛查诊断流程特别是心脏听诊和经皮氧饱和度联合筛查有利于早期发现新生儿CHD，值得推广应用。     

抗逆转录病毒药对孕育期雌鼠心血管影响*

目的: 评价抗逆转录病毒药对孕育期雌性大鼠心血管功能及某些生化指标的影响。方法: SD大鼠9周龄雌鼠19只、10周龄雄鼠6只,9只/10只雌鼠与3只雄鼠合1笼,共2笼,分为正常对照组(CON)、高效抗逆转录病毒治疗组(HARRT)。其中CON组雌性大鼠每天早、晚生理盐水 (10 ml/kg)灌胃,HARRT组雌性大鼠灌等容积抗逆转录病毒药(AZT 31.25 mg/kg +3TC 15.63 mg/kg +LPV/r (41.67/10.42) mg/kg),连续3个月。记录雌性大鼠体重、存活情况;检测超声心动图,多导生理记录仪检测动脉血压、心脏血流动力学参数;相应试剂盒检测血糖、血脂四项、心肌酶及肝酶;Masson染色及透射电镜分别观察心肌胶原纤维和心肌细胞超微结构。结果: CON组雌性大鼠均存活(9/9),HARRT组雌性大鼠存活6只(6/10);与CON组比较,HAART组雌性大鼠体重减少(P＜ 0.01);LVDd、IVST、LVPWT、LAD增加(P＜0.05);动脉舒张压增加(P＜0.05)、LVP +dP/dt_max减少(P＜0.01);TG减少、Glu增加(P＜0.05)、CK减少(P＜0.01)、GOT减少(P＜0.05);心肌组织胶原纤维增多,心肌细胞超微结构异常。结论: 抗逆转录病毒药可导致孕育期雌性大鼠心血管病变。     

重组腺相关病毒载体相关性杂质

可以稳定表达治疗基因而无明显不良反应的重组腺相关病毒(rAAV)载体被认为是最有发展前景的基因治疗载体。但如何建立可以有效去除rAAV载体内具有潜在致病危害的杂质、产品质量符合临床使用要求的纯化工艺是研究人员面临的巨大挑战。其中针对载体相关性杂质的纯化工艺尤为关键,因为该类杂质的性质与真正的rAAV载体极其相似,一旦存在便难以去除,且会引起严重不良反应。以下总结了该类杂质形成的过程及有别于rAAV载体的特点,并对可以防止其生成或将其与rAAV载体有效分离的技术手段进行了评价。