Primary central nervous system lymphoma (PCNSL) is a rare highly aggressive brain tumor originating from the extranodal sites, with a low 5-year overall survival rate. Some patients may have drug resistance or relapse, the therapeutic regimens based on high-dose methotrexate is insufficient to meet the clinical treatment needs. With the in-depth study of characteristics of lymphoma-related genes and immune microenvironment, new pathways continue to emerge, including Bruton tyrosine kinase inhibitors, immune preparations such as lenalidomide, anti-programmed death receptor-1 antibodies, chimeric antigen receptor T-cell therapy, etc. This review focuses on the progress of targeted drugs and immunotherapy for PCSNL.

Objective:To investigate the expression and significance of endoplasmic reticulum stress apoptosis pathway related proteins in renal cortex of rats with chronic fluorosis.Methods:Twenty four healthy SD rats were divided into 4 groups (6 rats/group, half male and half female) according to their body mass (100 - 120 g) by random number table method, rats in control group drank tap water (fluoride content < 0.5 mg/L), and in low, medium and high fluoride groups drank tap water with fluoride content (sodium fluoride) of 10, 50 and 100 mg/L, respectively. After 180 days of feeding, dental fluorosis was examined, 24-hour urine sample was collected and the content of fluoride in urine was detected by fluoride ion selective electrode method. Renal tissue was taken after anesthesia, and the pathological changes of renal cortex were observed by hematoxylin-eosin (HE) staining. The expressions of endoplasmic reticulum stress apoptosis pathway related proteins [inositol-requiring enzyme 1α (IRE1α), apoptosis signal-regulating kinase 1 (ASK1), C-Jun N-terminal kinase (JNK) and phosphorylated JNK (P-JNK)] were determined by immunohistochemical staining in rat renal cortex.Results:No dental fluorosis was found in control group. The incidence of dental fluorosis in low, medium and high fluoride groups were 2/6, 5/6 and 6/6, respectively. Compared with control group [(5.707 ± 1.190) mg/L], the urinary fluoride in low, medium and high fluoride groups [(17.028 ± 3.006), (34.378 ± 12.045), (94.759 ± 31.773) mg/L] was significantly higher ( P < 0.05), and the urinary fluoride in high fluoride group was higher than that in low and medium fluoride groups ( P < 0.05). HE staining showed that, compared with control group, the cell volume of renal tubules and glomeruli in medium and high fluoride groups increased, the cells arranged closely, and the eosinophilia of the cytoplasm increased. The immunohistochemical staining results showed that there was no significant difference in the expression of JNK protein in rat renal cortex between control group and low, medium and high fluoride groups ( F = 0.07, P > 0.05). The expressions of IRE1α, ASK1 and P-JNK proteins in rat renal cortex in high fluoride group were higher than those of control, low and medium fluoride groups ( P < 0.05), and the expressions of IRE1α and ASK1 proteins in medium fluoride group were significantly higher than those in control and low fluoride groups ( P < 0.05). Conclusion:Long-term excessive fluoride intake can lead to renal cortex injury in rats, and the mechanism of injury may be related to the activation of IRE1α-ASK1-JNK endoplasmic reticulum stress apoptosis pathway.

Animals ; Mice ; Motor Neurons/physiology* ; Spinal Cord

The lung is an important organ in systemic toxicity test of medical devices and is significant in safety evaluation. Based on the authors' understanding of medical devices, this study provides a brief analysis of the lung examination and common problems in systemic toxicity, so as to provide references for the pre-clinical safety evaluation of medical devices. It should be noted that a reasonable risk assessment should be made after comprehensive assessment for specific medical device products.
Equipment Safety ; Humans ; Lung ; Risk Assessment

Diffuse large B-cell lymphoma (DLBCL) is a group of heterogeneous diseases, and further classification is of great value for prognostic stratification. In recent years, some subtypes with poor prognosis have been recognized, such as "double-hit" lymphoma or "double-expressing" lymphoma. In addition, the new molecular classification provides a new perspective for the accurate diagnosis and prognosis stratification of DLBCL. The mutation and deletion of p53 gene are high risk factors in the traditional sense of DLBCL, while with the application of the next generation sequencing and other technologies, the influence of more accurate gene mutation or deletion on prognosis and its prognostic value in new cell molecular subtypes still need to be further confirmed. This paper reviews the progress of cell phenotypes and molecular subtypes as well as p53 gene abnormalities in the prognosis of DLBCL.

Objective:To investigate the clinicopathological and molecular biological characteristics of patients with plasma cell tumor.Methods:The data of bone marrow fluid, bone marrow tissue, peripheral blood and urine specimens of 84 patients with plasma cell tumor from January 2016 to October 2018 in Shanxi Provincial People's Hospital were collected. Bone marrow fluid was examined by using bone marrow smear, karyotype analysis, fluorescence in situ hybridization (FISH), immunophenotyping, and next-generation sequencing (NGS). In addition to the observation of cell morphology, peripheral blood together with urine specimens was also determined by using immune-fixation electrophoresis and free light chain examination. Bone marrow tissue was used to observe the structure and fibrosis of bone marrow, and relevant histochemistry and immunohistochemistry was also performed.Results:Among 84 patients with plasma cell tumor, 2 patients (2.4%) were monoclonal gammopathies of un-determined significance (MGUS), 78 patients (92.8%) were multiple myeloma (MM) (38 cases were IgG Kappa type, 33 cases were IgG Lambda type, 2 cases were IgA Kappa type, 1 case was IgA Lambda type, 3 cases were light chain type, 1 case was non-secretory type), 3 cases (3.6%) were Waldenstrom macroglobulinemia (WM), and 1 case (1.2%) was non-secretory myeloma (NSM). The proportion of abnormal plasma cells detected by bone marrow smear was 0.132-0.676 in 81 patients, and the proportion of abnormal monoclonal plasma cells detected by flow cytometry (FCM) was 1.1%-52.4% in 79 patients. Immunohistochemistry and FCM detection of bone marrow showed positive or weak positive results of CD38 and CD138. Complex karyotype was rare in karyotype analysis. FISH examination showed IGH isolation in 24 patients (28.6%) and gene detection showed 1 case was positive IGH-CCND1 and 1 case was positive IGH-MAF; 1 case of free light chain examination was positive. The positive rate of NGS was lower.Conclusion:Most plasma cell tumors are IgG type, followed by IgA type. Light chain type of plasma cell tumors is rare, and IgM type and non-secretory type are extremely rare. The morphological manifestations of bone marrow smear cytology in different clone types are different.

Dbait is a small double-stranded DNA molecule that has been utilized as a radiosensitizer to enhance the sensitivity of glioma to radiotherapy (RT). However, there is no effective drug delivery system to effectively overcome the blood-brain barrier (BBB). The aim of this study was to develop a gene delivery system by using the BBB and glioma dual-targeting and microenvironment-responsive micelles (ch-K(s-s)R8-An) to deliver Dbait into glioma for RT. Angiopep-2 can target the low-density lipoprotein receptor-related protein-1 (LRP1) that is overexpressed on brain capillary endothelial cells (BCECs) and glioma cells. In particular, due to upregulated matrix metalloproteinase 2 (MMP-2) in the tumor microenvironment, we utilized MMP-2-responsive peptides as the enzymatically degradable linkers to conjugate angiopep-2. The results showed that ch-K(s-s)R8-An micelles maintained a reasonable size (80-160 nm) with a moderate distribution and a decreased mean diameter from the cross-linking as well as exhibited low critical micelle concentration (CMC) with positive surface charge, ranging from 15 to 40 mV. The ch-K5(s-s)R8-An/pEGFP showed high gene transfection efficiency , improved uptake in glioma cells and good biocompatibility and . In addition, the combination of ch-K5(s-s)R8-An/Dbait with RT significantly inhibited the growth of U251 cells . Thus, ch-K5(s-s)R8-An/Dbait may prove to be a promising gene delivery system to target glioma and enhance the efficacy of RT on U251 cells.

Objective To explore the effect of nursing intervention based on the transtheoretical model and stages of change on breastfeeding knowledge, self-efficacy, and duration of breastfeeding in newly born pregnant women, aimed to provide reference for breastfeeding behavior health education model for pregnant women. Methods The 130 primiparas who came to the hospital graded a class- three of Shanxi Province for perinatal examination were selected as the research subjects from May to June in 2017 , they were divided into test group and control group by random digits table method. In the control group, the normal breastfeeding health guidance was carried out in the three stages of prenatal, hospitalized and after discharge. The test group divided the primipara from the beginning of pregnancy to 6th months postpartum period into 5 stages according to transtheoretical model and stages of change. The new strategy of breastfeeding should be formulated and implemented according to different stages and behavior changing processes. Results The total score of breastfeeding knowledge of primipara were (8.76±1.14), (8.92±1.21), (9.90±1.27), (9.94±1.29) points in control group before intervention, the 3rd day, the 42nd day and the 6th month after delivery, and they were (9.11 ± 1.42), (12.02 ± 1.64), (13.04 ± 1.67), (15.00±1.83) points respectively in test group, the differences were statistically significant(Ftime= 51.823, Fgroup=10.406, Finteractive=56.641, all P < 0.05). The total scores of breastfeeding self-efficacy of primipara were (84.62 ± 1.14), (88.96 ± 1.41), (86.65 ± 1.47), (84.31 ± 1.57) points respectively in control group before intervention, the 3rd day, the 42nd day and the 6th month after delivery, while in test group they were (84.98 ± 1.20), (104.02 ± 1.42), (111.00 ± 1.45), (120.04 ± 1.40) points, the differences were statistically significan (Ftime=12.592, Fgroup=229.674, Finteractive=79.955, all P<0.05). The pure breastfeeding rates of primipara were 60.0％(33/55) , 41.8％(23/55), 21.8％(12/55) in control group on the 3rd day, the 42nd day and the 6th month after delivery, they were 84.7％(50/59), 76.3％(45/59) , 49.2％(29/59) in the test group. The differences was statistically significant (χ2=8.804, 14.038, 9.235, all P <0.01). Conclusion Breastfeeding intervention based on the theory of behavioral staged transition can help primipara to improve breastfeeding knowledge and self-efficacy, and improve breastfeeding status.

Objective To evaluate the clinical efficacy and safety of endoscopic submucosal dissection (ESD) guided with endoscopic ultrasonography (EUS) for rectal neuroendocrine neoplasms(NENs).Methods A retrospective analysis was performed on 58 patients with rectal ENEs who underwent ESD from January 2011 to December 2015 in JiangSu Province Hospital.Manifestations of EUS, clinicopathological characteristics, proliferation activity grade, complete resection rate, complications and follow-up results of lesion were studied.Results Those treated by ESD included 58 patients with 64 lesions of rectal NENs.EUS results showed that 3 lesions originated from mucosa, 3 from muscularis mucosa and 58 from submucosa.A total of 34 lesions located within 5 cm from anus, 26 in 6-10 cm from anus and 4 more than 10 cm from anus.All 64 lesions were successfully treated by ESD.The mean maximum diameter of the lesions was 0.8 cm(0.2-3.5 cm), and the mean procedure time was 31 min(10-60 min).The complete resection rate was 93.8% (60/64).There were 4 patients with positive basal surgical margin, and two of them underwent additional surgery and two others were treated with argon plasma coagulation after rejecting surgery and ESD.Histological examination determined that 59 lesions were pathologic grade 1(G1) and 5 were pathologic grade 2(G2).Delayed bleeding occurred in 4 cases after ESD,which was managed by medicine in 1 case and endoscopic treatment in 3 cases.No perforation occurred after ESD.During a mean follow-up period of 22.9 months(3-48 months), no lymph node metastasis or distant metastasis was observed.Conclusion EUS is able to distinguish the origin of rectal NENs and aid determining the range and depth of ESD.ESD appears to be a safe, feasible and effective procedure for providing accurate histopathologica1 evaluations as well as curative treatments for rectal NENs limited to submucosa.

Objective:To investigate the role of scavenger receptor BⅡ(SR-BⅡ) in the oxidized low density lipid(ox-LDL) induced foam cells formation promoted by porphyromonas gingivalis(P.g).Methods:Peritoneal macrophages were stimulated with P.g and ox-LDL,and then foam cells formation were checked.The expression of SR-BⅡ was detected by Western blot and real-time PCR.Next,siRNA targeting SR-BⅡ was used to detect the change of foam cells formation.Results:After being stimulated with P.g and ox-LDL,the foam cells formation was significantly increased.During the process of foam cells formation,P.g infection increased the expression of SR-BⅡ.And the knockdown of SR-BⅡ by siRNA significantly reduced the foam cells formation.Conclusion:P.g infection can increase the expression of SR-BⅡ and the regulation of SR-BⅡ expression can change the foam cells formation.