Transferrin-conjugated magnetic silica PLGA nanoparticles loaded with doxorubicin and paclitaxel for brain glioma treatment

The effective treatment of malignant brain glioma is hindered by the poor transport across the blood–brain barrier (BBB) and the low penetration across the blood-tumor barrier (BTB). In this study, transferrin-conjugated magnetic silica PLGA nanoparticles (MNP-MSN-PLGA-Tf NPs) were formulated to overcome these barriers. These NPs were loaded with doxorubicin (DOX) and paclitaxel (PTX), and their anti-proliferative effect was evaluated in vitro and in vivo. The in vitro cytotoxicity of drug-loaded NPs was evaluated in U-87 cells. The delivery and the subsequent cellular uptake of drug-loaded NPs could be enhanced by the presence of magnetic field and the usage of Tf as targeting ligand, respectively. In particular, cells treated with DOX-PTX-NPs-Tf with magnetic field showed the highest cytotoxicity as compared to those treated with DOX-PTX-NPs-Tf, DOX-PTX-NPs, DOX-PTX-NPs-Tf with free Tf. The in vivo therapeutic efficacy of drug-loaded NPs was evaluated in intracranial U-87 MG-luc2 xenograft of BALB/c nude mice. In particular, the DOX-PTX-NPs-Tf treatment exhibited the strongest anti-glioma activity as compared to the PTX-NPs-Tf, DOX-NPs-Tf or DOX-PTX-NPs treatment. Mice did not show acute toxicity after administrating with blank MNP-MSN-PLGA-Tf NPs. Overall, MNP-MSN-PLGA-Tf NPs are promising carriers for the delivery of dual drugs for effective treatment of brain glioma.     

腓肠肌外侧头纤维化钙化与膝及小腿后外侧疼痛

目的：探讨腓肠肌外侧头纤维化、钙化引起膝后及小腿后外侧疼痛的临床特点及治疗方法。方法：收集腓肠肌外侧头纤维化、钙化导致膝及小腿后外侧疼痛病例25例（28侧）,其中侧位X线片于股骨外侧髁后部可见明显的小豆骨22侧,仅见小钙化点6侧;均行钙化或纤维化组织包块切除,腓总神经探查松解术。结果：全部病例随访6-24个月,平均12个。术后静态及动态一过性足下垂及小腿下段与足背麻木症状消失,膝关节后外侧疼痛消失或明显缓解。结论：腓肠肌外侧头纤维化钙化是膝后外疼痛的重要原因,大多伴有腓总神经受损症状,目前对其认识欠缺,误诊率高,手术切除纤维化钙化包块、选择松解受累的腓总神经效果确切。     

Distribution of eight blood-group systems and ABH secretion in Mongolian,Korean, and Zhuang nationalities in China

Among different blood-group systems investigated here, the distribution of the ABO system varies most of all, followed by MNSs and P. Although there are differences in ABH secretion in the different populations, no striking regularity has been found. No significant difference has been found in the distribution of the blood-group systems Rhesus, Diego, Duffy, Kell and Kidd in these Chinese populations: the Rh (-) rate is less than 1%, the frequencey of Di^a is about 0·04, the frequency of Fy^a is rather high, the frequency of K extremely low and Jk^a is about 0·4.

In the three nationalities under study, Mongolians are characterized by a high frequency of I^B, M higher than 0·5 and a relatively high frequency of P₁. Koreans are characterized by a high frequency of I^A, slightly more M than N and rather high CDE in the Rh system. The peculiarities of the Zhuangs are a rather high frequency of I^O and M and the lowest frequency of P₁.     

IL-12 regulates bone marrow eosinophilia and airway eotaxin levels induced by airway allergen exposure

BACKGROUND: Airway allergen exposure causes local eosinophilic cell infiltration. This cellular inflammatory response is likely to involve the release of eosinophils from peripheral storage pools, and possibly also regeneration of eosinophils in the bone marrow. IL-12 is an inhibitory cytokine in allergic inflammation, shown to reduce eosinophilic cell infiltration. The aim of the present study was to determine whether airway allergen exposure increases bone marrow eosinophil production, and, if so, whether IL-12 modulates this effect. METHODS: Ovalbumin-sensitized C57BL/6 mice and IL-12 knockout (KO) mice were exposed to allergen via the airway route, and the inflammatory cell response was evaluated in bronchoalveolar lavage fluid, blood, and bone marrow. RESULTS: Allergen instillation intranasally produced a dose-dependent inflammatory response in the lower airways of sensitized mice. This inflammatory response was dominated by eosinophils, but there were also increases of both lymphocytes and neutrophils. Sensitization and airway allergen exposure also increased the IL-5-dependent growth of bone marrow cells in vitro. The enhanced bone marrow responsiveness in vitro was paralleled by an increased number of bone marrow eosinophils in vivo. After sensitization and repeated allergen exposure, IL-12 KO mice showed higher eosinophil levels in both BAL and bone marrow than parallel wild-type control mice. Furthermore, BAL-eotaxin levels were increased in IL-12 KO mice as opposed to parallel wild-type controls after allergen exposure. CONCLUSIONS: Airway allergen exposure induced systemic immunologic responses, including increased eosinophil numbers in both airways and bone marrow, and also enhanced IL-5 responsiveness in bone marrow cells. IL-12 may regulate airway eosinophilia at both the level of eosinophilopoiesis and the level of local recruitment of eosinophils into the airways.     

CD8+ T cell survival in lethal fungal sepsis was ameliorated by T-cell-specific mTOR deletion

Lethal fungal sepsis causes high morbidity and mortality in intensive care patients. Fungal infections have an immunological basis, and it has been shown in recent studies that decreased CD8⁺ T-cell count in fungal infections is related to prognosis, while the underlying mechanism is still unclear. Here, a lethal fungal sepsis model induced by candidemia was created and we found a decreased CD8⁺ T-cell count and exaggerated apoptosis. Simultaneously, expression of light chain (LC)3B in CD8⁺ T cells increased, along with increased autophagosomes and accumulation of p62 in infected mice. We regulated the activity of the mammalian target of rapamycin (mTOR) pathway using T-cell-specific mTOR/ TSC1 deletion mice. We observed increased number of autophagosomes and expression of LC3B in CD8⁺T cells after T-cell-specific mTOR knockout, while accumulation of p62 was not ameliorated, and there was no increase in the number of autolysosomes. Apoptosis rate and expression of BIM, a pro-apoptotic gene, decreased in CD8⁺ T cells in mTOR-deletion mice but increased in TSC1-deletion mice. Our results showed increased CD8⁺ T-cell death in spleen of lethal fungal sepsis mice, and decreased expression of mTOR ameliorated CD8⁺ T-cell survival. mTOR may be a possible target to reverse CD8⁺ T-cell immune dysfunction in lethal fungal sepsis.     

Determination of Bioelectrical Impedance Thresholds for Early Detection of Breast Cancer-related Lymphedema

Background: Bioelectrical impedance technology is a common technique used for the early detection of breast cancer-related lymphedema (BCRL). However, studies on the threshold value established by Inbody 720 device (Biospace, Korea) have been extremely limited. We aimed to determine its reference range and cutoff values.Methods: All patients were recruited from October 2017 to October 2019 at the Peking University People''s Hospital Breast Center. In total, 82 patients with unilateral BCRL and 1305 healthy subjects were recruited in this study. We measured the extracellular fluid (ECF) ratio, extracellular water (ECW) ratio, as well as the single-frequency bioimpedance analysis (SFBIA) ratios at 1 and 5 kHz with the Inbody 720 device. The Youden index-based cutoff points, mean + 2SD and mean + 3SD values of these four indicators for both dominant and nondominant arms were also calculated.Results: Data were collected from 1387 women, including healthy subjects and patients with lymphedema. All statistical analyses were performed with SPSS. Significant differences were found between the two groups in the ECW, ECF, and SFBIA ratios. For the dominant affected arms, the Youden index-based cutoff points for the ECF, ECW, as well as SFBIA ratios at 1 and 5 kHz were 1.009, 1.008, 1.068, and 1.068, respectively. For the nondominant affected arms, the Youden index-based cutoff points were 1.014, 1.013, 1.047, and 1.048, respectively. The mean + 2 standard deviations (SD) and mean + 3SD values were also calculated.Conclusions: We determined the Youden index-based cutoff points, mean + 2SD and mean + 3SD values of the ECF, ECW, as well as SFBIA ratios at 1 and 5 kHz for both dominant and nondominant arms with data from 1305 healthy subjects. Next, the Youden index-based cutoff points, the mean + 2SD and mean + 3SD values were used to recognize patients with lymphedema. We found that the Youden index-based cutoff points and the mean + 2SD showed similar identification capacity on lymphedema, and they seemed to distinguish more patients with lymphedema than mean + 3SD values.     

矽尘致肺泡巨噬细胞氧化损伤的超微结构和细胞化学研究

目的：探讨矽尘致肺泡巨噬细胞损伤过程中是否存在着氧化损伤机制。方法：对矽尘作用于肺泡巨噬细胞产生的Ｏ＾－２和Ｈ２Ｏ２进行原位显示、定量测定并做相关分析;以ＡＴＰａｓｅ作为膜功能酶改变的反映;在亚细胞水平观察细胞形态结构。结果：细胞形态结构受损程度、膜ＡＴＰａｓｅ的活性与矽尘肺泡巨噬细胞早期产生的氧自由基活性直接相关。结论：（１）首次将原位显示氧自由基技术应用于矽尘致肺泡巨噬细胞损伤机制研究,发现氧