Progress of research on PD-1/PD-L1 in leukemia

Leukemia cells prevent immune system from clearing tumor cells by inducing the immunosuppression of the bone marrow (BM) microenvironment. In recent years, further understanding of the BM microenvironment and immune landscape of leukemia has resulted in the introduction of several immunotherapies, including checkpoint inhibitors, T-cell engager, antibody drug conjugates, and cellular therapies in clinical trials. Among them, the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis is a significant checkpoint for controlling immune responses, the PD-1 receptor on tumor-infiltrating T cells is bound by PD-L1 on leukemia cells. Consequently, the activation of tumor reactive T cells is inhibited and their apoptosis is promoted, preventing the rejection of the tumor by immune system and thus resulting in the occurrence of immune tolerance. The PD-1/PD-L1 axis serves as a significant mechanism by which tumor cells evade immune surveillance, and PD-1/PD-L1 checkpoint inhibitors have been approved for the treatment of lymphomas and varieties of solid tumors. However, the development of drugs targeting PD-1/PD-L1 in leukemia remains in the clinical-trial stage. In this review, we tally up the basic research and clinical trials on PD-1/PD-L1 inhibitors in leukemia, as well as discuss the relevant toxicity and impacts of PD-1/PD-L1 on other immunotherapies such as hematopoietic stem cell transplantation, bi-specific T-cell engager, chimeric antigen receptor T-cell immunotherapy

Reproducibility of quantitative flow ratio: An inter-core laboratory variability study

Background: Quantitative flow ratio (QFR) is a novel approach to derive fractional flow reserve (FFR) from coronary angiography. This study sought to evaluate the reproducibility of QFR when analyzed in independent core laboratories. Methods: All interrogated vessels in the FAVOR II China Study were separately analyzed using the AngioPlus system (Pulse medical imaging technology, Shanghai) by two independent core laboratories, following the same standard operation procedures. The analysts were blinded to the FFR values and online QFR values. For each interrogated vessel, two identical angiographic image runs were used by two core laboratories for QFR computation. In both core laboratories QFR was successfully obtained in 330 of 332 vessels, in which FFR was available in 328 vessels. Thus, 328 vessels ended in the present statistical analysis. Results: The mean difference in contrast-flow QFR between the two core laboratories was 0.004 ± 0.03 (p = 0.040), which was slightly smaller than that between the online analysis and the two core laboratories (0.01 ± 0.05, p < 0.001 and 0.01 ± 0.05, p = 0.038). The mean difference of QFR with re­spect to FFR were comparable between the two core laboratories (0.002 ± 0.06, p = 0.609, and 0.002 ± 0.06, p = 0.531). Receiver operating characteristic curve analysis showed that diagnostic accuracies of QFR analyzed by the two core laboratories were both excellent (area under the curve: 0.970 vs. 0.963, p = 0.142), when using FFR as the reference standard. Conclusions: The present study showed good inter-core laboratory reproducibility of QFR in assessing functionally-significant stenosis. It suggests that QFR analyses can be carried out in different core labo­ratories if, and only if, highly standardized conditions are maintained

Identification of PLATZ genes in Malus and expression characteristics of MdPLATZs in response to drought and ABA stresses

Plant AT-rich sequences and zinc-binding proteins (PLATZ) play crucial roles in response to environmental stresses. Nevertheless, PLATZ gene family has not been systemically studied in Rosaceae species, such as in apple, pear, peach, or strawberry. In this study, a total of 134 PLATZ proteins were identified from nine Rosaceae genomes and were classified into seven phylogenetic groups. Subsequently, the chromosomal localization, duplication, and collinearity relationship for apple PLATZ genes were investigated, and segmental duplication is a major driving-force in the expansion of PLATZ in Malus. Expression profiles analysis showed that PLATZs had distinct expression patterns in different tissues, and multiple genes were significantly changed after drought and ABA treatments. Furthermore, the co-expression network combined with RNA-seq data showed that PLATZ might be involved in drought stress by regulating ABA signaling pathway. In summary, this study is the first in-depth and systematic identification of PLATZ gene family in Rosaceae species, especially for apple, and provided specific PLATZ gene resource for further functional research in response to abiotic stress

Comparison of metabolic syndrome prevalence and characteristics using five different definitions in China: a population-based retrospective study

BackgroundMetabolic syndrome (MetS) is on the rise in developing countries and is characterized by a series of indications of metabolic disturbance. However, the prevalence of MetS varies under different definitions. The study aimed to compare five definitions of MetS in the China adult population, to explore their prevalence, characteristics and agreement.MethodsThe data for the retrospective study came from the China Health and Retirement Longitudinal Study (CHARLS), consisting of 9,588 participants (≥45). MetS definitions from International Diabetes Federation (IDF) (2006), National Cholesterol Education Program Adult Treatment Panel III (ATPIII) (2005), National Cholesterol Education Program Adult Treatment Panel III (ATPIII) (2001), Chinese Diabetes society (CDS) (2004) and the World Health Organization (WHO) (1999). We used binary and multivariable logistic analysis to explore factors connected with MetS.ResultsThe five definitions of MetS led to different prevalence of MetS:34.52% by IDF (2006), 38.63% by ATP (2005), 25.94% by ATP (2001), 26.31% by CDS (2004), 21.57% by WHO (1999). According to the definition of IDF (2006) (22.32% vs. 45.06%), ATPIII (2005) definition (27.99% vs. 47.82%), ATPIII (2001) definition (15.37% vs. 35.07%), CDS (2004) definition (19.96% vs. 31.80%), and WHO (1999) definition (17.44% vs. 25.14%), the prevalence of MetS in men was low but in women was high. The agreement between the five definitions for men was good except for the IDF (2006) definition and ATPIII (2001) definition (kappa = 0.51), with kappa values from 0.64 to 0.85. For women, the agreement between the five definitions was good ranging from 0.67 to 0.95, however, except for the definition of CDS (2004) and the definition of IDF (2006) (kappa = 0.44), the definition of WHO (1999) and the definition of IDF (2006) (kappa = 0.55), and the definition of WHO (1999) and the definition of ATPIII (2005) (kappa = 0.54). Binary logistic analysis indicated that although the impact and relevance varied by sex and definition, age, education, marital status, current residence, current smoking, alcohol using, taking activities and number of chronic diseases were factors connected to MetS.Conclusionthe prevalence and characteristics of the five definitions of MetS are different in the Chinese population. Therefore, it is vital to use the same definition for a country to diagnose MetS. On the other side, a lower prevalence in men than in women and the consistency of five MetS definitions are good in men but relatively poor in women

Gene SH3BGRL3 regulates acute myeloid leukemia progression through circRNA_0010984 based on competitive endogenous RNA mechanism

Introduction: Acute myeloid leukemia (AML) is a malignant proliferative disease affecting the bone marrow hematopoietic system and has a poor long-term outcome. Exploring genes that affect the malignant proliferation of AML cells can facilitate the accurate diagnosis and treatment of AML. Studies have confirmed that circular RNA (circRNA) is positively correlated with its linear gene expression. Therefore, by exploring the effect of SH3BGRL3 on the malignant proliferation of leukemia, we further studied the role of circRNA produced by its exon cyclization in the occurrence and development of tumors.Methods: Genes with protein-coding function obtained from the TCGA database. we detected the expression of SH3BGRL3 and circRNA_0010984 by real-time quantitative polymerase chain reaction (qRT-PCR). We synthesized plasmid vectors and carried out cell experiments, including cell proliferation, cell cycle and cell differentiation by cell transfection. We also studied the transfection plasmid vector (PLVX-SHRNA2-PURO) combined with a drug (daunorubicin) to observe the therapeutic effect. The miR-375 binding site of circRNA_0010984 was queried using the circinteractome databases, and the relationship was validated by RNA immunoprecipitation and Dual-luciferase reporter assay. Finally, a protein‐protein interaction network was constructed with a STRING database. GO and KEGG functional enrichment identified mRNA-related functions and signaling pathways regulated by miR-375.Results: We identified the related gene SH3BGRL3 in AML and explored the circRNA_0010984 produced by its cyclization. It has a certain effect on the disease progression. In addition, we verified the function of circRNA_0010984. We found that circSH3BGRL3 knockdown specifically inhibited the proliferation of AML cell lines and blocked the cell cycle. We then discussed the related molecular biological mechanisms. CircSH3BGRL3 acts as an endogenous sponge for miR-375 to isolate miR-375 and inhibits its activity, increases the expression of its target YAP1, and ultimately activates the Hippo signaling pathway involved in malignant tumor proliferation.Discussion: We found that SH3BGRL3 and circRNA_0010984 are important to AML. circRNA_0010984 was significantly up-regulated in AML and promoted cell proliferation by regulating miR-375 through molecular sponge action

Community trauma exposure and post-traumatic stress disorder in Chinese children and adolescents

BackgroundAn increasing number of studies have shown the association between traumatic events occurring in childhood and adolescence and post-traumatic stress disorder (PTSD). A gap remains in the literature on the epidemiology and influencing factors of traumatic events and post-traumatic stress disorder in communities in northern China. This study aimed to determine the prevalence of traumatic events and PTSD in communities in northern China, to explore the types of stressful traumatic events and the impact of these traumatic events on children and adolescents, and to investigate the effect of sociodemographic factors on PTSD.MethodsA cross-sectional survey study was conducted among 6,027 students (7–17 years old) from 6 cities in Liaoning Province, China. The sample consisted of 2,853 males (47.34%) and 3,174 females (52.66%). The Essen Trauma-Inventory for Children and Adolescents (ETI-CA) Scale was used. The ETI-CA has 5 sections, which include type of traumatic events, worst traumatic event, post-traumatic symptoms, onset, duration, burden of PTSD, and present difficulties in different areas of life. PTSD symptoms were assessed with 23 items in Part 3 of the ETI-CA.ResultsWe found that 2,068 (34.3%) of 6,027 participants experienced trauma events and 686 (33.2%) of 2,068 reported PTSD. Among trauma-exposed youth (2,068), the sudden death of close relatives (33.9%), serious accidents (20.9%), and parental divorce (15.5%) were reported as the worst traumatic events. Studies have shown that after exposure to stressful life events, more than 30% of people feel nervous or upset (39.8%), scared (33.4%), helpless (32.6%), and about 10% have headaches (15.5%), rapid heartbeat (13.3%), and dizziness (11.8%). Multivariable logistic regression analyses showed that students in middle school [OR = 1.29 (1.016, 1.637)], not a student leader [OR = 0.738 (0.618, 0.881)], and their parents in single marital status significantly predicted higher PTSD prevalence the remarried [OR = 0.474 (0.252, 0.893)], married [OR = 0.42 (0.227, 0.778)].ConclusionThe present study suggests the government to train psychological counselors in schools and communities to provide emotional and psychological support, as well as the school leaders and parents to elevate adolescents' psychological suzhi. Particularly, counseling and professional support should be given to those students whose parents are single

The Role of Osteopontin and Its Gene on Glucocorticoid Response in Myasthenia Gravis

Biomarkers that assess treatment response for patients with the autoimmune disorder, myasthenia gravis (MG), have not been evaluated to a significant extent. We hypothesized the pro-inflammatory cytokine, osteopontin (OPN), may be associated with variability of response to glucocorticoids (GCs) in patients with MG. A cohort of 250 MG patients treated with standardized protocol of GCs was recruited, and plasma OPN and polymorphisms of its gene, secreted phosphoprotein 1 (SPP1), were evaluated. Mean OPN levels were higher in patients compared to healthy controls. Carriers of rs11728697*T allele (allele definition: one of two or more alternative forms of a gene) were more frequent in the poorly GC responsive group compared to the GC responsive group indicating an association of rs11728697*T allele with GC non-responsiveness. One risk haplotype (AGTACT) was identified associated with GC non-responsiveness compared with GC responsive MG group. Genetic variations of SPP1 were found associated with the response to GC among MG patients

Predicting depressive symptom by cardiometabolic indicators in mid-aged and older adults in China: a population-based cross-sectional study

ObjectiveDepressive symptom is a serious mental illness often accompanied by physical and emotional problems. The prevalence of depressive symptom in older adults has become an increasingly important public health priority. Our study used cardiometabolic indicators to predict depressive symptom in middle-aged and older adults in China.MethodsThe data came from the China Health and Retirement Longitudinal Study 2011 (CHARLS2011), which was a cross-sectional study. The analytic sample included 8,942 participants aged 45 years or above. The study evaluated the relationship between cardiometabolic indicators and depression by measuring 13 indicators, including body mass index (BMI), waist circumference, waist-height ratio (WHtR), conicity index, visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), a body shape index (ABSI), body roundness index (BRI), triglyceride glucose index (TyG-index) and its correlation index (TyG-BMI, TyG-waist circumference, TyG-WHtR). Binary logistic regression analysis was used to examine the association between thirteen cardiometabolic indicators and depressive symptom. In addition, the receiver operating characteristic (ROC) curve analysis and area under curve (AUC) were used to evaluate the predictive anthropometric index and to determine the optimum cut-off value.ResultsThe study included 8,942 participants, of whom 4,146 (46.37%) and 4,796 (53.63%) were male and female. The prevalence of depressive symptom in mid-aged and older adults in China was 41.12% in males and 55.05% in females. The results revealed that BMI [AUC = 0.440, 95%CI: 0.422–0.457], waist circumference [AUC = 0.443, 95%CI: 0.425–0.460], WHtR [AUC = 0.459, 95%CI: 0.441–0.476], LAP [AUC = 0.455, 95%CI: 0.437–0.472], BRI [AUC = 0.459, 95%CI: 0.441–0.476], CVAI [AUC = 0.449, 95%CI: 0.432–0.467], TyG-BMI [AUC = 0.447, 95%CI: 0.429–0.465], and TyG-waist circumference [AUC =0.452, 95%CI: 0.434–0.470] were weak predictors of depressive symptom (p < 0.05) in males. In females, BMI [AUC = 0.470, 95%CI: 0.453–0.486], LAP [AUC = 0.484, 95%CI: 0.467–0.500], TyG-BMI [AUC = 0.470, 95%CI: 0.454–0.487], and TyG-waist circumference [AUC =0.481, 95%CI: 0.465–0.498] were weak predictors of depressive symptom (p < 0.05). On the other side, VAI, ABSI, conicity index and TyG index could not predict depressive symptom in middle-aged and older adults.ConclusionMost cardiometabolic indicators have important value in predicting depressive symptom. Our results can provide measures for the early identification of depressive symptom in middle-aged and older adults in China to reduce the prevalence of depressive symptom and improve health

TRABAJOS DE MÉTODO ARQUEOLÓGICO [Material gráfico]

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte, 201

Thalamic Activation Modulates the Responses of Neurons in Rat Primary Auditory Cortex: An In Vivo Intracellular Recording Study

Auditory cortical plasticity can be induced through various approaches. The medial geniculate body (MGB) of the auditory thalamus gates the ascending auditory inputs to the cortex. The thalamocortical system has been proposed to play a critical role in the responses of the auditory cortex (AC). In the present study, we investigated the cellular mechanism of the cortical activity, adopting an in vivo intracellular recording technique, recording from the primary auditory cortex (AI) while presenting an acoustic stimulus to the rat and electrically stimulating its MGB. We found that low-frequency stimuli enhanced the amplitudes of sound-evoked excitatory postsynaptic potentials (EPSPs) in AI neurons, whereas high-frequency stimuli depressed these auditory responses. The degree of this modulation depended on the intensities of the train stimuli as well as the intervals between the electrical stimulations and their paired sound stimulations. These findings may have implications regarding the basic mechanisms of MGB activation of auditory cortical plasticity and cortical signal processing