[摘 要] 目的：制备并表征包载CPI-444并偶联CD8抗体的纳米微粒（CNP/αCD8），探讨其对CD8+ T细胞活化、增殖和抗肿瘤作用的影响。方法: 采用复乳溶剂蒸发法和EDC/NHS法制备包载腺苷受体A2A（A2AR）特异性拮抗剂CPI-444（C）或香豆素6（C6）荧光素的纳米微粒并分别在其表面偶联CD8抗体，制得CNP/αCD8和C6NP/αCD8。扫描电镜和NanoPlus粒度测定仪表征纳米微粒形态和粒径，液相色谱与串联质谱联用（LC-MS/MS）法和离心法测定纳米微粒的载药量和药物释放情况，荧光显微镜和流式细胞仪检测CD8+ T细胞内化C6NP/αCD8的情况，流式细胞仪、ELISA和LDH法检测CNP/αCD8对CD8+ T细胞增殖、活化、细胞毒活性和杀瘤能力的影响。结果: CNP/αCD8纳米微粒为圆形、粒径约150 nm，能有效包载CPI-444和偶联CD8抗体，药物包封率和CD8抗体偶联效率分别约为60%和53.4%；CNP/αCD8纳米微粒具有良好稳定性，能被CD8+ T细胞内化，抑制A2AR分子表达。生物学功能实验显示，CNP/αCD8增强CD8+ T细胞的增殖能力、促进T细胞活化、分泌细胞因子及产生颗粒酶B和穿孔素，并增强CD8+ T细胞杀伤肿瘤细胞的能力。结论: CNP/αCD8纳米微粒能显著增强CD8+ T细胞免疫效应功能，其增强CD8+ T细胞功能可能是通过抑制A2AR分子的表达起作用。

OBJECTIVETo detect the expression levels of Livin and Caspase-3 proteins in diffuse large B cell lymphoma (DLBCL), and to explore its correlation with clinicopathological characteristics, so as to provide a reference for clinical treatment and evaluation prognosis of DLBCL.

METHODSImmunohisto-chemical staining was performed to detect the expression of Livin and Caspase-3 in the samples from 51 DLBCL patients and 20 patients with reactive hyperplasia of lymph node (RHL). The relation between Livin and Caspase-3 with the factors influencing the prognosis of DLBCL was analyzed.

RESULTSLivinwas not expressed in the tissues of RHL, but its expression rates reached to 58.82%(30/51) in 51 cases of DLBCL(P<0.05). The expression rats of Caspase-3 in DLBCL and RHL were 25.49%(13/51) and 85.0%(17/20) respectively, and the difference was statistically significant(P<0.05). The expression level of Livin in DLBCL tissues was related with clinical stage and pathological type(P<0.01, P<0.01). The expression of Livin was not obviously related with sex, age and extranodal involvement. The expression level of Caspase-3 in DLBCL tissues was related with clinical stage (P<0.05). The expression of Caspase-3 was not obviously related with sex, age, pathological type and extranodal involvement. There was a negative correlation between Livin and Caspase-3 in DLBCL(γ=-0.333,P=0.017). Kaplan-meier survival analysis revealed that the expressions of Livin and Caspase-3 were related stalistically significantly with the patients prognosis (P<0.01, P<0.05).

CONCLUSIONOver-expression of Livin in DLBCL and DLBCL of non-GCB subtypes, and low-expression of Caspase-3 in DLBCL may play a significant role in clinical prognosis of DLBCL.

OBJECTIVETo explore the feasibility and clinical effect of posterior spinal canal decompression with pedicle screw fixation and reconstruction of anterior and middle vertebral column for thoracolumbar burst fractures complicated with nerve injury.

METHODSA total of 36 patients with thoracolumbar burst fractures treated from March 2011 to April 2016 were enrolled in the retrospective study. There were 20 males and 16 females, aged from 21 to 52 years old with an average of 37.6 years. All the fractures were located on a single segment, 8 cases of T11₁₁, 10 cases of T₁₂, 12 cases of L₁, 6 cases of L₂. According to thoracolumbar injury classification and severity score(TLICS) system, the score was 7 to 9 points, with an average of 7.4 points. According to the America Spine Injury Association(ASIA) grade, 4 cases were type A, 10 cases were type B, 14 cases were type C, 8 cases were type D. All the patients underwent posterior spinal canal decompression with pedicle screw fixation and reconstruction of anterior and middle vertebral column. The recovery of nerve function was evaluated by ASIA grading. The correction of kyphosis(Cobb angle), the volume change of injuried spinal canal, the change of anterior border height of injury vertebra which can be observed by X-rays;the internal fixation loosening and breakage and all the information of bone fusion were recorded.

RESULTSAll the operations were successful, the mean operative time and intraoperative blood loss were(2.8±0.3) h (2.1 to 3.5 h) and (880±120) ml(550 to 1 350 ml), respectively. All the incisions got primary healing. All the patients were followed up for 12 to 28 months with an average of 18.4 months. All the patients obtained satisfactory bone fusion. No pseudoarticulation formation was found, and there was no loosening, breakage of pedicle screws or displacement of titanium mesh. Neurological function was improved in different degree, except in one patient with grade A and another one with grade B. According to the ASIA grade, there were 1 case of type A, 1 case of type B, 7 cases of type C, 10 cases of type D and 17 cases of type E, postoperatively. At 3 days after operative, the anterior border height of injury vertebra, Cobb angle and the volume changes of injury spinal canal were obviously improved(<0.05), and there was no significant difference between postoperative at 3 days and final follow-up(>0.05).

CONCLUSIONSSpinal canal decompression with screw fixation and reconstruction of anterior and middle vertebral column through posterior midline approach is a safe and effective method in the treatment of thoracolumbar burst fractures with nerve injury, it is worthy to be popularized. It can complete the spinal canal decompression of 360 degree, reduction of fractures and reconstruction of vertebral three-column at the same time through a single posterior approach. The advantages includes less trauma, perfect decompression, good stability and etc.

Adult ; Bone Screws ; Decompression, Surgical ; Female ; Fracture Fixation, Internal ; Humans ; Lumbar Vertebrae ; injuries ; Male ; Middle Aged ; Retrospective Studies ; Spinal Canal ; Spinal Fractures ; surgery ; Thoracic Vertebrae ; injuries ; Treatment Outcome ; Young Adult

Objective To study the role of ubiquitin proteasome pathway in Du Meridian moxibustion for skeletal muscle aging. Methods A total of 30 Sprague-Dawley rats were randomly separated into control group (n=10), model group (n=10) and moxibustion group (n=10). The model group and the moxibustion group were subcutaneously injected D-galactose 125 mg/kg daily for six weeks, while the control group was injected the same volume of saline. Then the moxibustion group was cauterized on Du Meridian 20 minutes a day for 20 days. The expression of ubiquitin, muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx) in erector spinae were tested with Western blotting. Results The expression of ubiquitin, MuRF1 and MAFbx increased in the model group compared with that of the control group (P<0.05), decreased in the moxibustion group compared with that of the model group (P<0.05).Conclusion The Du Meridian moxibustion may regulate ubiquitin proteasome pathway to inhibit the degradation of protein, and delay muscular atrophy.

OBJECTIVE: To understand the iron stores of the plateletpheresis donors, so as to provide some new experimental data for further exploration and more perfect health examination criteria of the plateletpheresis donors. METHODS: A total of 297 plateletheresis donors conformed to standard in October 2018 were selected by the cross sectional study. The related factors affecting iron stores were analyzed; the effect of plateletpheresis times of donation on the levels of the hemoglobin(Hb) and serum ferritin(SF) as well as the iron deficency rate in the blood donors was also analyzed; the iron stores in the blood donors was evaluated. RESULTS: The SF level in plateletpheresis donors negatively correlated with annual plateletphersis times of donation（r=-0.416, P＜0.001）; The SF level decreased with the increase of annual times of donation（P＜0.05）; The iron deficiency rate in plateletpheresis donors showed the increase trend with the increase of annual times of donation. The iron deficiency rate in male and femal with 18-23 times of donation was 12.5%(8/64) and 40%(6/15) respectively. CONCLUSION The blood center should reduce recruitment frequency and increase the testing of SF for regularly plateletpheresis donors.
Blood Donors ; Cross-Sectional Studies ; Ferritins ; Hemoglobins ; Humans ; Iron ; Male ; Plateletpheresis

Retinitis pigmentosa(RP)was known as pigmentation retinitis even. RP is a group of hereditary eye diseases that cause irreversible visual impairment due to progressive loss of function of retinal pigment epithelial cells and progressive apoptosis of photoreceptors. Because of its heterogeneity in phenotype and heredity and complex pathogenesis, there is currently no single effective treatment. This article mainly elaborates on the progress in the treatment of retinitis pigmentosa in recent years.

Objective: The aim of this study was to update the epidemic situation of dengue fever (DF) and provide new insights for the consideration of disease control in Fujian province, China. Methods: Details about DF cases in Fujian reported during 2004-2017 were collected and analyzed. The envelope (E) genes of isolates of dengue virus (DENV) were sequenced for phylogenetic analysis. Results: The number of imported DF cases had increased dramatically since 2013, and the source regions expanded from Southeast Asia to South Asia, America, Oceania, and Africa, as well as the surrounding provinces. This resulted in local outbreaks and indigenous cases of DF that occurred more frequently, with 10 of 13 local outbreaks and 85.9% (1,252/1,458) of indigenous cases reported in 2013-2017. Compared with only two coastal cities before 2013, four coastal and one inland city in 2013-2017 experienced the local DF outbreaks. The phylogenetic analysis of E genes confirmed that the import of DENV, not only from abroad but also from the surrounding provinces, played an important role in dissemination and local outbreaks of DF in Fujian. Conclusions The frequent import of DF cases from not only abroad but also the surrounding provinces resulted in increased incidence, frequent local outbreaks, and expansion of distribution in Fujian in recent years. There is a need for urgent measures to improve disease control in this province.

OBJECTIVETo explore the effect of a novel emodin derivative E19 on proliferation inhibition and apoptosis induction of human chronic myelogenous leukemia (CML) cell line K562 and imatinib-resistant CML cell line (K562/G01), and to clarify the involved mechanisms.

METHODSMTT and colony formation test were used to detect the cell proliferation. Apoptotic induction effects were examined by DAPI staining method and DNA ladder assay. Western blot was performed to detect the changes of P210(Bcr-Abl) protein.

RESULTSThe emodin derivative E19 could efficiently inhibit proliferation and induce apoptosis in K562 and K562/G01 cells. IC50 of K562 cells and IC50 of K562/G01 cells were (1.20 ± 0.19) µmol/L and (1.22 ± 0.16) µmol/L, respectively. DNA fragmentation in K562 cells and K562/G01 cells confirmed that the E19 induced apoptosis in dose-dependent manner. Western blot showed that emodin derivative inhibited phosphorylation of P210 protein in K562 cells and K562/G01 cells and down-regulated the expression level of P210 in dose- and time-dependent manners.

CONCLUSIONThe emodin derivative E19 can efficiently inhibit growth and induce apoptosis of K562 cells and K562/G01 cells, while the inhibition of phosphorylation of P210 protein and down-regulation of P210 protein expression may be involved in these processes.

Apoptosis ; drug effects ; Cell Proliferation ; Down-Regulation ; Drug Resistance, Neoplasm ; Emodin ; analogs & derivatives ; pharmacology ; Fusion Proteins, bcr-abl ; metabolism ; Humans ; Imatinib Mesylate ; pharmacology ; K562 Cells ; drug effects ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; pathology ; Phosphorylation

BACKGROUND: Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS's response to SD. METHODS: Middle-aged wild-type (WT) C57BL/6 and CX3CR1-/- mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes. RESULTS: CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1-/- S group, the CX3CR1-/- SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted. CONCLUSIONS These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.
Animals ; Cognitive Dysfunction ; Mice ; Mice, Inbred C57BL ; Microglia ; Neuroinflammatory Diseases ; Sleep Deprivation

Neuropathic pain is a common chronic pain that affects human health worldwide. As an important mediator of excitatory conduction in neurons, ion channels are important targets for mechanism research and drug research in this field. T-type calcium channel(Cav3) can be activated transiently when neurons are close to the resting potential of -70 mV, resulting in a transient Ca