腰椎穿刺术后体位管理对病人影响的研究进展

讨论腰椎穿刺术后头痛的影响因素,对护理常规规定的腰椎穿刺后采取去枕平卧4～6 h提出质疑.许多研究表明,腰椎穿刺术后垫枕、侧卧或俯卧位均不会增加头痛的发生率,卧床时间长短对头痛也无明显影响,而采取去枕平卧可导致压疮、腰背痛等不适.因此,腰椎穿刺术后去枕平卧可能并非必需.     

β-hydroxy-β-methylbutyrate Improves Chronic Renal Failure-Induced Sarcopenia in SD Rats by Regulating Autophagy

Background Chronic renal failure-induced sarcopenia (CRF-S) seriously affects public health by increasing morbidity and mortality.This study evaluated the thera...     

Effect of Electromagnetic Field on Wear Resistance of Fe901/Al2O3 Metal Matrix Composite Coating Prepared by Laser Cladding

Fe901/Al₂O₃ metal matrix composite (MMC) coatings were deposited on the surface of 45 steel via electromagnetic field (EF)-assisted laser cladding technology. The influences of EF on the microstructure, phase composition, microhardness, and wear resistance of the Fe901/Al₂O₃ MMC coating were investigated. The generated Lorentz force (F_L) and Joule heating due to the application of EF had a positive effect on wear resistance. The results showed that F_L broke up the columnar dendrites. Joule heating produced more nuclei, resulting in the formation of fine columnar dendrites, equiaxed dendrites, and cells. The EF affected the content of hard phase in the coatings while it did not change the phase composition of the coating, because the coatings with and without EF assistance contained (Fe, Cr), (Fe, Cr)₇C₃, Fe₃Al, and (Al, Fe)₄Cr phases. The microhardness under 20 mT increased by 84.5 HV_0.2 compared to the coating without EF due to the refinement of grains and the increased content of hard phase. Additionally, the main wear mechanism switched from adhesive wear to abrasive wear.     

黛力新联合高压氧治疗脑供血不足致睡眠障碍的临床效果观察

目的:观察黛力新联合高压氧治疗脑供血不足致睡眠障碍的临床效果.方法:选取2018年8月至2020年12月山东省临沂市兰陵县人民医院收治的脑供血不足致睡眠障碍患者90例作为研究对象,运用随机数字表法分为观察组与对照组,每组45例,对照组患者采用常规药物治疗及高压氧治疗,观察组患者采用黛力新联合高压氧治疗,比较2组治疗效果...     

阻断血吸虫病传播策略与措施专家共识

2015年全国达到血吸虫病传播控制标准后,进入以全面阻断血吸虫病传播为新目标、开展监测预警为主要干预措施的新时期.“十三五”时期,四川、江苏、云南、湖北等4个血吸虫病防治重点省份先后达到血吸虫病传播阻断标准或通过国家血吸虫病传播阻断技术评估,我国血吸虫病疫情处于历史最低水平,流行程度进一步降低,《“十三五”全国血吸虫病...     

D-mannose facilitates immunotherapy and radiotherapy of triple-negative breast cancer via degradation of PD-L1

Breast cancer is the most frequent malignancy in women worldwide, and triple-negative breast cancer (TNBC) patients have the worst prognosis and highest risk of recurrence. The therapeutic strategies for TNBC are limited. It is urgent to develop new methods to enhance the efficacy of TNBC treatment. Previous studies demonstrated that D-mannose, a hexose, can enhance chemotherapy in cancer and suppress the immunopathology of autoimmune diseases. Here, we show that D-mannose can significantly facilitate TNBC treatment via degradation of PD-L1. Specifically, D-mannose can activate AMP-activated protein kinase (AMPK) to phosphorylate PD-L1 at S195, which leads to abnormal glycosylation and proteasomal degradation of PD-L1. D-mannose–mediated PD-L1 degradation promotes T cell activation and T cell killing of tumor cells. The combination of D-mannose and PD-1 blockade therapy dramatically inhibits TNBC growth and extends the lifespan of tumor-bearing mice. Moreover, D-mannose–induced PD-L1 degradation also results in messenger RNA destabilization of DNA damage repair–related genes, thereby sensitizing breast cancer cells to ionizing radiation (IR) treatment and facilitating radiotherapy of TNBC in mice. Of note, the effective level of D-mannose can be easily achieved by oral administration in mice. Our study unveils a mechanism by which D-mannose targets PD-L1 for degradation and provides methods to facilitate immunotherapy and radiotherapy in TNBC. This function of D-mannose may be useful for clinical treatment of TNBC.

Breast cancer is the most common type of cancer in women all over the world and is curable in most early-stage, nonmetastatic patients (∼70 to 80%) (1). Triple-negative breast cancer (TNBC), which is characterized by absence of the molecular markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) and accounts for ∼15 to 20% of all breast cancer cases (2, 3), has the worst prognosis compared to other subtypes, and the 5-y survival rate for these women if they do not present with metastatic disease is 65 to 90% depending on the disease stage at diagnosis. TNBC is highly invasive and has the highest risk of distant metastasis (∼46%) (1, 4). Notably, the median survival time of patients after metastasis is only 13.3 mo (4). The therapeutic strategies for TNBC are very limited. Until 2019, TNBC treatment was still restricted to chemotherapy (2). Over the past 2 y, immunotherapy, in combination with chemotherapy, has been applied in TNBC treatment and has shown promising results, but a large number of TNBC patients are nonresponsive or resistant to immunotherapy. In addition, radiotherapy can also improve locoregional control of breast cancer. However, TNBC shows resistance to radiotherapy, and radiotherapy did not change the local recurrence rate of TNBC (5). Overall, TNBC treatment is still a challenge, and exploring appropriate systematic treatments and improving the efficacy of immunotherapy and radiotherapy are important goals of breast cancer research.Programmed death ligand 1 (PD-L1, also called B7-H1) is a 33-kDa protein located either on the cell membrane or in the cytoplasm. Membrane-localized PD-L1 can inhibit the proliferation and cytolytic activity of T cells to help cancer cells escape from immune surveillance via interaction with its receptor programmed cell death protein 1 (PD-1) on immune cells (6, 7). Immune checkpoint blockade therapy has been a focus of cancer research and treatment in recent years (8). Immunotherapies targeting PD-1/PD-L1 have shown substantial clinical benefits in different tumor types (9, 10). In addition to its well-established role as an immune checkpoint molecule, intracellular PD-L1 also acts as an RNA-binding protein and competes with RNA exosomes to increase RNA stability globally. Specifically, PD-L1 in the cytoplasm binds with messenger RNAs (mRNAs) of several DNA damage repair (DDR)-related genes and protects them from degradation, which facilitates the DDR and enhances tumor resistance to DNA-damaging therapy (11).Glycosylation is one of the most important posttranslational modifications (PTMs) (12). Glycans have been shown to play different biological roles in glycoproteins, such as assisting correct folding, targeting proteins to specific receptors, controlling the residence time in the bloodstream, and regulating the function of proteins (13). N-glycosylation is one of the most common glycosylation forms on proteins. N-linked glycans are covalently attached to proteins at the asparagine residue of the NXT motif (Asn-X-Ser/Thr) when the new proteins are being translated and transported into the endoplasmic reticulum. All N-glycans share a common core sequence and are further classified into three types: high D-mannose, hybrid, and complex glycans (14, 15). It has been reported that complex N-glycan exists on the extracellular domain of PD-L1 and that PD-L1 is N-glycosylated at N35, N192, N200, and N219 in cancer cells (16), which promotes its stability and suppresses T cell activity. Glycosylation of PD-L1 is also essential for the PD-L1/PD-1 interaction and immunosuppression in TNBC (17). Interestingly, metformin, a drug widely used for the treatment of type 2 diabetes, was reported to induce abnormal glycosylation and degradation of PD-L1 (18).D-mannose, a C-2 epimer of glucose, is the major monosaccharide component of N-glycans and is internalized into mammalian cells via membrane glucose transporters (19). Once taken into cells, D-mannose is phosphorylated by hexokinase (HK) and produces mannose-6-phosphate (M6P), which can be directed into glycolysis or glycosylation pathway (20). Previous studies demonstrated that a supraphysiological level of D-mannose could enhance the sensitivity of cancer cells to chemotherapy (21) and suppress the immunopathology of autoimmune diabetes and airway inflammation (22). D-mannose has also been shown to oppose macrophage activation by impairing IL-1-β production (23). More recently, D-mannose was reported to suppresses oxidative response and block phagocytosis in experimental neuroinflammation (24). However, the function of D-mannose in immunotherapy and radiotherapy in cancer remains unknown. Here, we demonstrated that D-mannose can target PD-L1 for degradation by impairing its glycosylation via AMPK activation. Importantly, oral administration of D-mannose decreased PD-L1 levels in mice, which promoted antitumor immunity and sensitized TNBC to radiotherapy.     

脐血来源内皮祖细胞的生物学特性与安全性评价

目的:探讨脐血来源的内皮祖细胞(endothelial progenitor cells,EPCs)的生物学特性,评价其长期体外培养后的安全性.方法:分离脐血单个核细胞(mononuclear cells,MNCs),采用MCDB1 31.培养基联合VEGF等生长因子进行培养.观察培养细胞的形态,测定其生长动力学,采用流式细胞仪及免疫细胞化学方法检测其表型,应用细胞荧光化学法分析EPCs对乙酰化低密度脂蛋白(acetylated low-density lipoprotein,ac-LDL)的摄取功能,Matrigel上培养并检测其形成血管能力,染色体核型分析其遗传稳定性,裸鼠实验、软琼脂实验观察致瘤性.结果:脐血来源的内皮祖细胞体外进行长期传代培养,群体倍增水平可达42代,有内皮细胞表面抗原的表达,具有内吞ac-LDL的功能和结合UEA-1的特性及体外形成血管的能力,分离培养的EPCs不同代次的内皮细胞均具有正常核型,并未见致瘤性.结论:脐血来源的内皮祖细胞具有较高的增值潜能,在体外传代可以大量扩增,长期传代时核型稳定,无致瘤性,是作为细胞治疗和基因治疗的理想种子细胞.     

D–π–A type conjugated indandione derivatives: ultrafast broadband nonlinear absorption responses and transient dynamics

The ultrafast nonlinear optical response of two 1,3-indandione derivatives (INB3 and INT3) was systematically investigated by the femtosecond Z-scan and pump-probe technique at multiple visible and near infrared wavelengths. Both compounds show strong broadband nonlinear absorption (NLA) and different wavelength-dependent two-photon absorption (TPA) characteristics in the range of 650–1100 nm. The TPA cross section of trithiophene-based compound INT3 was found to be larger than that of triphenylamine-based compound INB3 in the red region (650–800 nm), which is attributed to its longer π-conjugated structure and better molecular planarity. Interestingly, the effective NLA of INB3 was found to be larger than INT3 in the NIR region (800–1100 nm), which is related to the excited state absorption (ESA) induced by TPA. The ultrafast dynamics of both compounds were investigated by femtosecond transient absorption spectroscopy, which revealed a broadband ESA including several relaxation processes. This work extends nonlinear optical research on indandione derivatives, and the results suggest that these derivatives are promising candidates for optical limiting applications.

In the red region (650–800 nm), the nonlinear absorption of trithiophene-based compound INT3 is greater than that of triphenylamine-based compound INB3, while in the NIR region (800–1100 nm), the strength of nonlinear absorption is the opposite.     

Molecular dynamics simulations of the initial oxidation process on ferritic Fe–Cr alloy surfaces

Oxidation processes of metallic interconnects are crucial to the operation of solid oxide fuel cells (SOFCs), and ferritic Fe–Cr alloy is one of the most important metallic interconnect materials. Based on the ReaxFF reactive potential, the interaction of O₂ molecules with three types of surfaces (100, 110, 111) of ferritic Fe–Cr alloy has been studied by classical molecular dynamics at constant O₂ concentrations and temperatures. The initial oxidation process is systematically studied according to the analysis of O₂ absorption rate, charge variations, charge distributions, mean squared distributions, and oxidation rate. The results reveal that it is easier and faster for the Cr atoms to lose electrons than for the Fe atoms during the oxidation process. The obtained oxidation rate of Cr atoms is larger and the formation of Cr₂O₃ takes precedence over that of FeO. And the thickness of oxidation layers of different surfaces could be determined quantitatively. We also find that the high O₂ concentration accelerates the oxidation process and obviously increases the thickness of oxidation layers, while the temperature has a weaker effect on the oxidation process than the O₂ concentration. Moreover, the (110) surface presents the best oxidation resistance compared to the other two surfaces. And the (110) surface is efficient in preventing Fe atoms from being oxidized. Here we explore the initial oxidation process of Fe–Cr alloy and the corresponding results could provide theoretical guides to the related experiments and applications as metallic interconnects.

Based on the ReaxFF reactive potential, the interaction of O₂ molecules with three types of surfaces (100, 110, 111) of ferritic Fe–Cr alloy has been studied by classical molecular dynamics at constant O₂ concentrations and temperatures.     

小鼠谷胱甘肽S转移酶K1启动子荧光素酶报告基因的构建及功能鉴定

目的:构建小鼠谷胱甘肽S转移酶K1(mGSTK1)启动子荧光素酶报告基因质粒,并分析其活性。方法:根据GeneBank中mGSTK1基因序列设计引物,应用PCR技术扩增mGSTK1启动子片段,插入pGL3-basic载体,获得mGSTK1启动子报告基因质粒pGL3-mGSTK1-2046。再以pGL3-mGSTK1-2046为模板,进一步构建了2个5’端部分缺失的报告基因质粒:pGL3-mGSTK1-936和pGL3-mGSTK1-76。将构建的报告基因质粒瞬时转染不同的细胞株3T3-L1和人胚肾(HEK)293,48 h后检测荧光素酶的活性。结果:所构建的质粒经酶切、测序鉴定正确。pGL3-mGSTK1-2046在3T3-L1和HEK293中均有不同程度的转录活性。将pGL3-mGSTK1-2046、pGL3-mGSTK1-936和pGL3-mGSTK1-76转染HEK293细胞,结果显示pGL3-mGSTK1-936转录活性最高,而pGL3-mGSTK1-76转录活性显著降低。结论:成功构建mGSTK1启动子荧光素酶报告基因质粒;翻译起始点上游的-971～-111 bp片段是mGSTK1启动子的重要区域。为深入了解mGSTK1启动子的调控机制以及今后对代谢性疾病的治疗提供一定的实验基础。