Developing universal CARs with improved flexible targeting and controllable activities is urgently needed. While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct universal CAR-T cells, the weak affinity between them is one of the limiting factors for efficacy. Herein, we systematically investigated the impact of Fcγ receptor (FcγR) affinity on CAR-T cells properties by constructing universal CARs using Fcγ receptors with different affinities for IgG1 antibodies, namely CD16a, CD32a, and CD64. We demonstrated that the activities of these universal CAR-T cells on tumor cells could be redirected and regulated by IgG1 antibodies. In xenografted mice, 64CAR chimeric Jurkat cells with the highest affinity showed significant antitumor effects in combination with herceptin in the HER2 low expression U251 MG model. However, in the CD20 high expression Raji model, 64CAR caused excessive activation of CAR-T cells, which resulted in cytokine release syndrome (CRS) and the decline of antitumor activity, and 32CAR with a moderate affinity brought the best efficacy. Our work extended the knowledge about FcγR-based universal CAR-T cells and suggested that only the FcγRCAR with an appropriate affinity can offer the optimal antitumor advantages of CAR-T cells.

Immune checkpoint inhibitors(ICIs)have become the most widely used drugs in tumor immunotherapy, with ipilimumab and nivolumab as their representatives.However, the use of immune checkpoint inhibitors has brought about many immune-related adverse events, of which myocarditis is one of the most fatal adverse reactions.The pathogenesis of immune checkpoint inhibitor-associated myocarditis is not fully understood, mainly involving autoimmune T lymphocyte infiltration, regulatory T-cell dysfunction, cytokines, autoantibody production, genetic factors, the gut microbiome, etc.The treatment and management of immune checkpoint inhibitor-associated myocarditis require concerted efforts of multidisciplinary experts.

Objective To investigate the ratio of transfer cesarean section after trial of labor and maternal-fetal outcomes based on Robson classifications.Methods The delivery data by cesarean section in Third Affiliated Hospital of Guangzhou Medical University from January 1st,2009 to December 31st,2015 (gestational age ＞28 weeks and newborn birth weight ＞1 000 g) were retrospectively collected.The ratio of transfer cesarean section after trial of labor and maternal-fetal adverse outcomes were analyzed by weighted adverse outcome score in different Robson classifications.Results (1) The highest ratio of transfer cesarean section after trial of labor was classification 9 (all abnormal lies,including previous cesarean section and breech were excluded) reached 47.31％ (431/911),followed by classification 2 (nulliparous women with a single cephalic pregnancy,＞37 weeks gestation who had labour induced) accounted for 44.90％(409/911).(2)The tops of weighted adverse outcome score of transfer cesarean section after trial of labor were classification 10 (single cephalic pregnancy at ＜37 weeks gestation,including women with previous cesarean delivery) 24.55,classification 5 (single cephalic pregnancy multiparous women,with at least one previous cesarean delivery,＞37weeks gestation) 3.64.Conclusion Carefully evaluating the delivery mode and emphasizing the intrapartum management in nulliparous women with a single cephalic pregnancy,at ＞ 37 weeks gestation who had labour induced and trial of labor after cesarean section is essential to reduce the risk of adverse outcomes in transfer cesarean section after trial of labor.

Objective? To explore the influence of nurses' self-job competence and coping style on nurses' job burnout, and to provide guidance for nurses' occupational health. Methods? From February to September of 2017, a total of 367 nurses from three hospitals of Huzhou City were recruited in a cross-sectional survey. The Chinese version of the Six Dimension (6-D) Scale of Nursing Performance was used to measure the competency of nurses. The General Coping Style Scale were used to measure the coping style of nurses. Maslash Burnout Inventory-Human Service Survey (MBI-HSS) was used to assess the job burnout of nurses, and analyze the relationship between job competency, coping style and job burnout of nurses. A total of 367 questionnaires were distributed in this study, 301 valid questionnaires were collected, and the effective recovery rate was 92.33%. Results? In general coping style scale, the positive coping score of the 301 nurses was (1.68±0.61) and the negative coping score was (1.93±0.74). The 6-D scale were negatively correlated with emotional exhaustion, depersonalization and positive coping style in MBI-HSS (P＜0.05), positively correlated with personal emotion and positive coping style (P＜ 0.05). The coping style of nurses plays a mediating role in the influence of job competency on job burnout. The path coefficient of job competency on job burnout was 0.62 (P＜0.001). Job competency could explain 57.31% of job burnout variance. The path coefficient of coping style to job burnout was -0.41.The path coefficient of coping style to job burnout was -0.41 (P＜0.001). The path coefficient of job competency to job burnout was -0.51 (P＜ 0.001). Job competency and coping style could explain 21.57% variance of job burnout. The indirect effect of job competency on job burnout through coping style was -0.25(P＜0.001). Conclusions? The coping style makes part of the mediating effect on the relationship between job competence and job burnout. Nursing managers and educators should improve the competency of nurses in various aspects such as job competency training, coping style training, and so on. These may help nurses improve their positive coping style and reduce their professional burnout.

Objective To investigate the influences of IL-17 on regulatory T ( Treg) cells during Chlamydia trachomatis infection. Methods Wild-type ( WT) C57BL/6 mice and IL-17-/- mice were in-tranasally injected with 1×103inclusion forming units (IFU) of Chlamydia muridarum (Cm) to establish the mouse model of Chlamydia trachomatis respiratory tract infection. Mouse spleen and lung single cells were prepared. The percentages of CD4+CD25+T and CD4+CD25+Foxp3+T cells were detected by flow cytome-try. Expression of Foxp3 and TGF-β at mRNA level in lung was detected by RT-PCR. The levels of IL-10 in bronchoalveolar lavage fluid samples were detected by ELISA. Results Compared with the WT mice, the IL-17-/- mice had higher percentages of CD4+CD25+T and CD4+CD25+Foxp3+T cells in spleen and lung on the third day of Cm infection. Both of the expression of Foxp3 at mRNA level in lung and the secretion of IL-10 in bronchoalveolar lavage fluid were increased in IL-17-/- mice as compared with those in WT mice. No significant difference in the expression of TGF-β at mRNA level in lung tissues was found between the two groups. Conclusion IL-17 might inhibit the proliferation of Treg cells and the secretion of IL-10 in the very early stage of Cm respiratory tract infection.

BACKGROUND:Establishment of in vitro culture system of human placental microvascular endothelial cel s with high purity is very important. In recent studies, some scholars have successful y obtained a large number of placental microvascular endothelial cel s by three-stepenzyme digestion and magnetic separation method, but the procedures were extremely complex and it had great damage to the cel s. Therefore, how to separate human placental microvascular endothelial cel s easily and obtain high-purified cel s has become a research hotspot.
OBJECTIVE:To investigate an efficient method to isolate and purify human placental microvascular endothelial cel s from early vil us microvessels, observe the cel growth and identify the cel s.
METHODS:The vil i from normal early pregnancies (6-8 weeks) after artificial abortion were col ected aseptical y. Using two-step digestion procedure and discontinuous Percol density gradient centrifugation method, human placental microvascular endothelial cel s were obtained. Then the cel s were identified by trypsin digestion method and repeated adherence method.
RESULTS AND CONCLUSION:Human placental microvascular endothelial cel s were isolated successful y from early vil i. The primary cel s adhered to the wal s after inoculated for 24 hours and entered logarithmic phase at 10 days. 80%of the cel s achieved a confluence at 12-13 days after inoculating. The subculture cel s grew swiftly with the typical cobblestone appearance. Immunofluorescence staining showed that, cultured human placental microvascular endothelial cel s demonstrated a strong positive reaction to von Wil ebrand factor antigen and CD31, accounting for 100%. MTT assay results showed that, human placental microvascular endothelial cel s at passage 5 exhibited an S-shaped growth curve. High-purity human placental microvascular endothelial cel s can be obtained by proteolytic enzymes digestion and discontinuous Percol density gradient centrifugation method, and the purity is detected by trypsin digestion method and repeated adherence method.

Objective To study the outcomes of selective reduction of triplet pregnancy by assisted reproductive technology. Methods The clinical data of 31 women who succeeded in conception by vitro fertilization-embryo transfer in the third affiliated hospital of Guangzhou Medical University were retrospectively investigated to analyze and compare the rates of abortion from triplet pregnancy, twin pregnancy and single pregnancy after selective reduction of triplet pregnancy, the incidence of pregnant complications, outcomes of perinatal period. Results There were no significant differences between triplet pregnancy and the twin and single pregnancy after selective reduction of triplet pregnancy in terms of pregnancy and parity time, fetal disease, premature rupture of membrane, severe eclampsism, gestational diabetes and postpartum hemorrhage (P>0.05). There were significant differences in gestational weeks, birth weight, rate of premature birth, rate of neonatal transfer to NICU and neonatal RDS: The gestational time in the triplet group longer than the groups of twin pregnancy and single pregnancy after selective reduction of triplet pregnancy (P<0.05). (37.3 ± 1.9) vs. (35.2 ± 0.9), (32.6 ± 2.3), respectively), the rate of premature birth dropped (100%vs. 100%, 33.3%, respectively), the body weight was increased (1 707 ± 360.4)g vs. (2 066.1 ± 307.5)g, (2 712.5 ± 514.1)g, respectively and the neonatal complication rate was reduced (P<0.05). Conclusion The selective reduction of multiple pregnancy may decrease the risk of premature birth and reduce the rate of lower body weight of neonates, improving the pregnancy outcomes, but the higher rate of abortion at the early or middle course of pregnancy after selective reduction is worth our attention.

Objective To explore the associated rules between western medicine and traditional Chinese medicine (TCM) on urinary tract infection (UTI) with text mining technique.Methods The data set on UTI was downloaded from CBM database.The regularities of Chinese patent medicines (CPM),western medicines and the combination of CPM and western medicines on UTI were mined out by data slicing algorithm.The results were showed visually with Cytoscape2.8 software.Results The main function of CPM was focused on clearing heat and removing toxicity,promoting diuresis and relieving stranguria.For western medicine,antibacterial agents was often used and it was also frequently used together with CPM such as Sanjinpian.Conclusions Text mining approach provides an important method in the summary of the application regularity for disease in both TCM and western medicine.

Objective To measure the nursing workload in ICU,and provide the basis for the scientific distribution of human resources and reasonable scheduling in ICU.Methods ICU patients of the First and Third People's Hospital of Zigong from July to September,2011 were selected.The TISS-28 and NAS were applied to measure the nursing workload in the ICU.The number of staff nurses on each day and on each shift was recorded.Results The total nursing workload and the per capita nursing workload for each day in a week showed no significant difference,and the per capita nursing workload of different shifts and the needs of nurse-patient ratio of different patients in ICU were significantly different.Conclusions The allocation of nursing staff should be balance for each day in a week and different shifts for each day.The configuration of the nursing human resources should be based on actual nursing workload,no only considering the species of the diseases,the disease condition,self-care ability and cooperation of the patients,but also the proficiency of nurse skills.

OBJECTIVETo investigate the effect of one kind of regulating-qi and Nourishing-yin Chinese herbs Zuoguiyin on the expression of rats ovarian vascular endothelial growth factor (VEGF) and secreted protein acidic rich in cysteine (SPARC) during the period of peri-menopause.

METHODThe animal models of perimenopause rats were established by natural aging. Perimenopause rats were treated by intragastric administration (ig) with low (13.78 g x kg(-1)), middle (20.67 g x kg(-1)) and high (31 g x kg(-1)) dose of Zuoguiyin for 8 weeks. Expression of VEGF and SPARC mRNA were detected by RT-PCR. Immunohistochemistry was used to evaluate expression levels of VEGF protein.

RESULTCompared with that in the control group, ovarian expression levels of VEGF mRNA and its protein in rats during peri-menopause increased significantly (P < 0.01). Middle and high dose of Zuoguiyin could both down-regulate the expression of VEGF in ovaries of praesenilis rats, and the difference has statistical significance (P < 0.01). Expression levels of SPARC mRNA in rat ovaries during peri-menopausal period decreased obviously compared to that in the control group (P < 0.01). Middle and high dose of Zuoguiyin could greatly promote ovarian SPARC mRNA expression of praesenilis rats (P < 0.01).

CONCLUSIONThe abnormal changes of VEGF and SPARC may play an important role in the aging process of ovary. Zuoguiyin, one kind of regulating-qi and Nourishing-yin Chinese herbs, can improve ovarian vascular formation through down-regulating the expression of VEGF meanwhile up-regulating the expression of SPARC. And it may delay aging by this way.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Female ; Gene Expression ; drug effects ; Humans ; Models, Animal ; Osteonectin ; genetics ; metabolism ; Ovary ; drug effects ; metabolism ; Perimenopause ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Vascular Endothelial Growth Factor A ; genetics ; metabolism