Trends in using mesenchymal stromal/stem cells (MSCs) in treating corneal diseases

Since their inception in the 1960s–70s, mesenchymal stem/stromal cells (MSCs) have gained interest because of their differentiation potential, anti-inflammatory effects, and immune-modulating properties. Both cell-based and cell-free MSC treatments show healing capacity in injured tissues. Cell-based treatment comprises MSCs and all secreted products, whereas cell-free treatments include only the secreted products. MSCs are therapeutically administered to many damaged organs owing to their efficacy. Specifically, the eye is a unique organ system to study the effects of MSCs, as treatment is easily applied and measured owing to its external location. The eye holds an immune-privileged status, wherein inflammation and immune responses are innately down-regulated. As excessive inflammation in the cornea often leads to fibrosis and irreversible corneal hazing, many studies have investigated the anti-inflammatory and immune-modulating capacities of MSCs. Decades of research suggest that MSCs modulate the immune response by secreting cytokines, growth factors, and extracellular matrix proteins that inhibit the infiltration of inflammatory cells following injury and promote a healing phenotype via M2 macrophage polarization. MSCs have also shown trans-differentiation potential into cornea-specific cell types during the wound healing process, such as corneal epithelial, stromal, or endothelial cells. This review discusses recent investigations of MSC treatment in the cornea, focusing on therapeutic efficacy, mechanisms, and future directions.     

What information can we gain from performing adaptive radiotherapy of head and neck cancer patients from the past 10 years?

The aim of the review was to present the current literature status about replanning regarding anatomical and dosimetric changes in the target and OARs in the head and neck region during radiotherapy, to discuss and to analyze factors influencing the decision for adaptive radiotherapy of head and neck cancer patients. Significant progress has been made in head and neck patients’ evaluation and qualification for adapted radiotherapy over the past ten years. Many factors leading to anatomical and dosimetric changes during treatment have been identified. Based on the literature, the most common factors triggering re-plan are weight loss, tumor and nodal changes, and parotid glands shrinkage. The fluctuations in dose distribution in the clinical area are significant predictive factors for patients’ quality of life and the possibility of recovery. It has been shown that re-planning influence clinical outcomes: local control, disease free survival and overall survival. Regarding literature studies, it seems that adaptive radiotherapy would be the most beneficial for tumors of immense volume or those in the nearest proximity of the OARs. All researchers agree that the timing of re-planning is a crucial challenge, and there are still no clear consensus guidelines for time or criteria of re-planning. Nowadays, thanks to significant technological progress, the decision is mostly made based on observation and supported with IGRT verification. Although further research is still needed, adaptive strategies are evolving and now became the state of the art of modern radiotherapy.     

The Risk of Alzheimer's Disease After Acute Appendicitis With or Without Appendectomy

ObjectivePrevious epidemiologic studies have suggested an association between appendectomy and Parkinson's disease. The aim of the current study was to examine the risk of Alzheimer's disease (AD) and other types of dementia following appendicitis or appendectomy for appendicitis.DesignPopulation-based cohort study.Setting and participantsWe used claims data from the Taiwan National Health Insurance Research Database. Participants aged ≥45 years with acute appendicitis or who received appendectomy for appendicitis were enrolled and followed up for more than 15 years. Cases and controls underwent 1:1 matching by age, sex, index date, and dementia-related comorbidities.MethodsThe primary outcome was AD, and secondary outcomes included other dementia types. Adjusted hazard ratios (aHRs) were calculated, and a competing risk regression model was created. The E value for causality of evidence was calculated.ResultsPatients developing appendicitis (0.6% vs 0.1%, P = .005) and those receiving appendectomy for appendicitis (0.4% vs 0.1%, P = .003) had higher incidences of AD than the controls during the follow-up period. A Cox regression analysis with adjustment for potential confounders showed that patients with appendicitis [aHR 6.68, 95% confidence interval (CI) 1.84-24.48] and those receiving appendectomy for appendicitis (aHR 5.01, 95% CI 1.33-18.85) were more likely to develop AD than the controls. These 2 groups also had higher risks for unspecified dementia and all types of dementia but not for vascular dementia than the controls. The age at dementia diagnosis was 88.51 years in the controls; however, among people who developed dementia following appendicitis, the mean age at diagnosis was 70.18 years, and dementia occurred 5.84 years after appendicitis. The competing risk regression models and the E values support the study findings.Conclusions and implicationsAfter recovery from appendicitis, these patients should be followed up for signs of AD.     

放疗干预对宫颈癌荷瘤小鼠的抑瘤作用及对Th1/Th2免疫细胞比例的影响

目的探讨放疗干预对宫颈癌荷瘤小鼠的抑瘤作用及其对辅助性T细胞1(Th1)/Th2细胞比例的影响。方法建立宫颈癌荷瘤小鼠模型,随机分为荷瘤组和放疗组,每组各10只,另设对照组10只。放疗组进行放疗干预14天,荷瘤组和对照组不治疗。放疗后4、6、8、10、12、14天测量肿瘤体积;末次治疗后,ELISA法测定血清干扰素-γ(IFN-γ)、白介素-2(IL-2)、IL-4、IL-10含量;计算抑瘤率、胸腺指数和脾脏指数;HE染色观察肿瘤组织学变化;TUNEL染色观察肿瘤组织细胞凋亡情况;流式细胞术检测脾脏Th1/Th2细胞比例;RT-qPCR和Western blot检测脾脏T盒子转录因子(T-bet)、GATA结合蛋白3(GABA-3)mRNA和蛋白表达。结果与荷瘤组比较,放疗组小鼠4、6、8、10、12、14天肿瘤体积及瘤质量减小,血清IL-2、IFN-γ升高,IL-4、IL-10降低,胸腺指数、脾脏指数升高,Th1细胞比例、Th1/Th2增加,Th2细胞比例减少,T-bet mRNA和蛋白及T-bet/GATA-3表达升高,GATA-3 mRNA和蛋白表达降低(P<0.05)。HE染色显示,荷瘤组肿瘤细胞数量较多,核大深染,无明显坏死;放疗组肿瘤细胞数量减少,出现大量坏死组织。TUNEL染色显示,荷瘤组TUNEL阳性细胞较少,放疗组TUNEL阳性细胞明显增多。结论放疗对宫颈癌荷瘤小鼠具有明显抑瘤作用,可能是通过调节T-bet/GATA-3表达,促进Th1/Th2分化平衡,增强机体免疫功能发挥作用。     

Post-aggression suicide under the influence of new psychoactive substances AMB–FUBINACA and U-47700

The objective of the present study was the development and validation of the method for determining AMB-FUBINACA and its metabolite - AMB-FUBINACA O-desmethyl acid – in blood samples, followed by verification of the method in toxicological judicial and forensic medicine practice employing the example of post-aggression suicide. Most likely in consequence of development of adverse effects resulting in psychotic symptoms, a male being under the influence of the synthetic cannabinoid AMB-FUBINACA and the new synthetic opioid U-47700, mortally wounded his female partner and subsequently committed suicide. Identification and determination of the afore-mentioned xenobiotics in blood samples collected from the male and female victims were performed employing high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The analytes were isolated from blood samples using the solid phase extraction (SPE) method. The blood samples collected from the male and female demonstrated respectively 110 and 196 ng/mL of AMB-FUBINACA O-desmethyl acid metabolite, 1935 and 357 ng/mL of U-47700, 250 and 200 ng/mL of N-desmethyl-U-47700, as well as 410 and 200 ng/mL of N,N-didesmethyl-U-47700. The concentration values of new psychoactive substances (NPS’s) in blood samples originating from the male and female were within the ranges encountered in cases of poisoning, including these resulting in death. Nevertheless, the evident signs of exsanguination proof that the woman was alive when she sustained lethal injuries. The presented cases illustrate the difficult to be anticipated effect exerted on the users by NPS’s.     

CD19+CD24hiCD38hi B细胞比例预测肝移植术后急性细胞性排斥反应发生的临床研究

目的分析肝移植术后受者外周血CD19⁺CD24^hiCD38^hi B细胞占单个核细胞比例变化情况及其与急性细胞性排斥反应(ACR)之间的关系。 方法回顾性分析2013年12月至2015年12月在浙江大学医学院附属第一医院接受心脏死亡器官捐献肝移植的80例成人受者临床资料，根据术后是否发生ACR，将受者分为ACR组(25例)和非ACR组(55例)。术前、术后各个时间点抽取参加研究者静脉血并分离外周血单个核细胞，加入异硫氰酸荧光素-单克隆鼠抗人CD19抗体、藻红蛋白-单克隆鼠抗人CD24抗体和别藻蓝蛋白-单克隆鼠抗人CD38抗体，流式细胞仪检测各组CD19⁺CD24^hiCD38^hi B细胞百分比。采用t检验和单因素方差分析比较正态分布计量资料，采用χ²检验比较计数资料，采用Kaplan-Meier法绘制受试者工作特征曲线(ROC曲线)。P<0.05为差异有统计学意义。 结果ACR组、非ACR组受者术前外周血平均CD19⁺CD24^hiCD38^hi B细胞比例分别为(3.13±0.91)%、(3.49±0.83)%，差异无统计学意义(t＝1.636，P>0.05)。ACR组术后发生ACR前外周血平均CD19⁺CD24^hiCD38^hi B细胞比例为(1.87±0.70)%。非ACR组受者术后3个月、6个月和1年外周血平均CD19⁺CD24^hiCD38^hi B细胞比例分别为(1.64±0.52)%、(1.63±0.56)%和(2.04±1.24)%，术后3、6个月平均值均低于术前和术后1年，差异均有统计学意义(P均<0.05)。ACR组受者发生ACR时外周血平均CD19⁺CD24^hiCD38^hi B细胞比例为(0.8±0.5)%，低于发生ACR前的平均水平(t＝5.752，P<0.05)，且低于非ACR组术后3个月、6个月和1年的平均水平(P<0.05)。ACR组受者接受抗排斥反应治疗后，CD19⁺CD24^hiCD38^hi B细胞比例也逐渐增加，ACR发生后7 d为(0.84±0.08)%，与ACR发生时相比差异无统计学意义(P>0.05)；而发生30 d后达(1.65±0.18)%，与ACR发生时相比差异有统计学意义(P<0.05)。当截断值为1.015%时，CD19⁺CD24^hiCD38^hi B细胞比例预测ACR发生的敏感度和特异度分别为0.786和0.702，ROC曲线下面积为0.775(95%CI: 0.671~0.879，P<0.05)。 结论CD19⁺CD24^hiCD38^hi B细胞比例下降与肝移植术后ACR反应发生有关，并可作为预测ACR发生的细胞标志物。