Interleukin-27 is positively correlated with obesity and a decrease in insulin resistance after weight loss.

OBJECTIVE: Interleukin-27 (IL-27), a potential mediator linking obesity to inflammatory diseases, is considered an important candidate for regulating obesity. The present study evaluated the relationship of IL-27 with obesity and insulin resistance (IR) and further investigated the changes in IL-27 levels after weight loss. METHODS: The study analyzed 405 participants, of whom 62 with overweight or obesity completed one year of lifestyle intervention. The body compositions, including percent of body fat (PBF), visceral fat area (VFA), skeletal muscle mass (SMM), and visceral fat area to skeletal muscle mass ratio (VSR), were assessed using the bioelectrical impedance analysis method. Serum IL-27 levels were measured using the enzyme-linked immunosorbent assay (ELISA). RESULTS: IL-27 levels increased significantly with the increase in body mass index (BMI) (P < 0.001). Moreover, IL-27 levels were positively correlated with PBF, VFA, and VSR. Homeostatic model assessment for insulin resistance (HOMA-IR), the inverse of hepatic insulin sensitivity (1/HISI), adipose tissue insulin resistance (Adipo-IR), and homeostasis model assessment-adiponectin (HOMA-AD) increased significantly with each quartile of IL-27 levels (all P < 0.001). IL-27 levels significantly decreased after weight loss (P < 0.001). CONCLUSIONS: IL-27 was positively correlated with obesity, HOMA-IR, 1/HISI, Adipo-IR, and HOMA-AD. IL-27 levels significantly decreased after weight loss.

Coupled Dynamic Characteristics of Mobile Ions in Halide Perovskites.

Mixed perovskites show immense promise for diverse applications owing to their exceptional compositional flexibility and outstanding optoelectronic performance. Nevertheless, a significant hurdle in their widespread use is their susceptibility to compositional instability. Some mixed perovskites exhibit a tendency to segregate into regions with varying halide content, negatively impacting the material's electronic properties and impeding its overall advancement. This study focuses on investigating the lattice and A-site cation dynamics in mixed-halide perovskites as well as the relationship between the stability and dynamic properties of mixed-halide perovskites. Our findings reveal an intrinsic link between the kinetics of organic molecules and halogen ion migration. The stability of halide ions is linearly positively correlated with the radius, number of H atoms, and moment of inertia of the organic molecules. Organic molecules with lower rotational kinetics effectively suppress the overall cationic kinetic activity, enhancing lattice dynamic stability in mixed perovskite systems. This inhibition further impedes the migration of halogen ions and hinders the halide segregation process. The presence of dominant I/MA vacancies in perovskites accelerates the rotation of MA and the migration of halogen ions. The coupled dynamic behavior of varying vacancy concentrations in A-site cations/X-site anions within the inorganic framework significantly impacts the photovoltaic performance of these halide perovskites.

Universal machine learning aided synthesis approach of two-dimensional perovskites in a typical laboratory.

The past decade has witnessed the significant efforts in novel material discovery in the use of data-driven techniques, in particular, machine learning (ML). However, since it needs to consider the precursors, experimental conditions, and availability of reactants, material synthesis is generally much more complex than property and structure prediction, and very few computational predictions are experimentally realized. To solve these challenges, a universal framework that integrates high-throughput experiments, a priori knowledge of chemistry, and ML techniques such as subgroup discovery and support vector machine is proposed to guide the experimental synthesis of materials, which is capable of disclosing structure-property relationship hidden in high-throughput experiments and rapidly screening out materials with high synthesis feasibility from vast chemical space. Through application of our approach to challenging and consequential synthesis problem of 2D silver/bismuth organic-inorganic hybrid perovskites, we have increased the success rate of the synthesis feasibility by a factor of four relative to traditional approaches. This study provides a practical route for solving multidimensional chemical acceleration problems with small dataset from typical laboratory with limited experimental resources available.

Cut-off values of haemoglobin and clinical outcomes in incident peritoneal dialysis: the PDTAP study.

BACKGROUND: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database. METHODS: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+). The secondary outcomes were the occurrences of hospitalization, first-episode peritonitis and permanent transfer to haemodialysis (HD). RESULTS: A total of 2591 PD patients were enrolled between June 2016 and April 2019 and followed up until December 2020. Baseline and time-averaged Hb <100 g/l were associated with all-cause mortality, MACE, MACE+ and hospitalizations. After multivariable adjustments, only time-averaged Hb <100 g/l significantly predicted a higher risk for all-cause mortality {hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.19-281], P = .006}, MACE [HR 1.99 (95% CI 1.16-3.40), P = .012] and MACE+ [HR 1.77 (95% CI 1.15-2.73), P = .010] in the total cohort. No associations between Hb and hospitalizations, transfer to HD and first-episode peritonitis were observed. Among patients with Hb ≥100 g/l at baseline, younger age, female, use of iron supplementation, lower values of serum albumin and renal Kt/V independently predicted the incidence of Hb <100 g/l during the follow-up. CONCLUSION: This study provided real-world evidence on the cut-off value of Hb for predicting poorer outcomes through a nation-level prospective PD cohort.

Influence of Organic-Cation Defects on Optoelectronic Properties of ASnI3 Perovskites A=HC(NH2 )2 , CH3 NH3.

Tin organic-inorganic halide perovskites (tin OIHPs) possess a desirable band gap and their power conversion efficiency (PCE) has reached 14 %. A commonly held view is that the organic cations in tin OIHPs would have little impact on the optoelectronic properties. Herein, we show that the defective organic cations with randomly dynamic characteristics can have marked effect on optoelectronic properties of the tin OIHPs. Hydrogen vacancies originated from the proton dissociation from FA [HC(NH2 )2 ] in FASnI3 can induce deep transition levels in the band gap but yield relatively small nonradiative recombination coefficients of 10-15  cm3 s-1 , whereas those from MA (CH3 NH3 ) in MASnI3 can yield much larger nonradiative recombination coefficients of 10-11  cm3 s-1 . Additional insight into the "defect tolerance" is gained by disentangling the correlations between dynamic rotation of organic cations and charge-carrier dynamics.

Eco-friendly inorganic molecular novel antiperovskites for light-emitting application.

The development of perovskite light-emitting diodes (PeLEDs) has progressed rapidly over the past several years, with high external quantum efficiencies exceeding 20%. However, the deployment of PeLEDs in commercial devices still faces severe challenges, such as environmental pollution, instability and low photoluminescence quantum yields (PLQYs). In this work, we perform high-throughput calculations to exhaustively search the unexplored and eco-friendly novel antiperovskite space (formula: X3B[MN4], with octahedron [BX6] and tetrahedron [MN4]). The novel antiperovskites have a unique structure whereby a tetrahedron can be embedded into an octahedral skeleton as a light-emitting center causing a space confinement effect, leading to the characteristics of a low-dimensional electronic structure, which then makes these materials potential light-emitting material candidates with a high PLQY and light-emitting stability. Under the guidance of newly derived tolerance, octahedral, and tetrahedral factors, 266 stable candidates are successfully screened out from 6320 compounds. Moreover, the antiperovskite materials Ba3I0.5F0.5(SbS4), Ca3O(SnO4), Ba3F0.5I0.5(InSe4), Ba3O0.5S0.5(ZrS4), Ca3O(TiO4), and Rb3Cl0.5I0.5(ZnI4) possess an appropriate bandgap, thermodynamic and kinetic stability, and excellent electronic and optical properties, making them promising light-emitting materials.

Application of pseudocontinuous arterial spin labeling perfusion imaging in children with autism spectrum disorders.

Introduction: Pseudocontinuous Arterial Spin Labeling (pCASL) perfusion imaging allows non-invasive quantification of regional cerebral blood flow (CBF) as part of a multimodal magnetic resonance imaging (MRI) protocol. This study aimed to compare regional CBF in autism spectrum disorders (ASD) individuals with their age-matched typically developing (TD) children using pCASL perfusion imaging. Materials and methods: This cross-sectional study enrolled 17 individuals with ASD and 13 TD children. All participants underwent pCASL examination on a 3.0 T MRI scanner. Children in two groups were assessed for clinical characteristics and developmental profiles using Autism Behavior Checklist (ABC) and Gesell development diagnosis scale (GDDS), respectively. We compared CBF in different cerebral regions of ASD and TD children. We also assessed the association between CBF and clinical characteristics/developmental profile. Results: Compared with TD children, individuals with ASD demonstrated a reduction in CBF in the left frontal lobe, the bilateral parietal lobes, and the bilateral temporal lobes. Within the ASD group, CBF was significantly higher in the right parietal lobe than in the left side. Correlation analysis of behavior characteristics and CBF in different regions showed a positive correlation between body and object domain scores on the ABC and CBF of the bilateral occipital lobes, and separately, between language domain scores and CBF of the left frontal lobe. The score of the social and self-help domain was negatively correlated with the CBF of the left frontal lobe, the left parietal lobe, and the left temporal lobe. Conclusion: Cerebral blood flow was found to be negatively correlated with scores in the social and self-help domain, and positively correlated with those in the body and object domain, indicating that CBF values are a potential MRI-based biomarker of disease severity in ASD patients. The findings may provide novel insight into the pathophysiological mechanisms of ASD.

Telemedicine and Clinical Outcomes in Peritoneal Dialysis: A Propensity-Matched Study.

INTRODUCTION: Telemedicine (TM) has shown to provide potential benefits on clinical outcomes in patients with chronic kidney disease but limited evidences published in the peritoneal dialysis (PD) population. This study aimed to explore the long-term effects of TM on the mortality and technique failure. METHODS: The Peritoneal Dialysis Telemedicine-assisted Platform Cohort Study (PDTAP Study) was conducted prospectively in 27 hospitals in China since 2016. Patient and practice data were collected through the doctor-end of the TM app (Manburs) for all participants. TM including self-monitoring records, on-line education materials, and real-time physician-patient contact was only performed for the patient-end users of the Manburs. The primary outcome was all-cause mortality. The secondary outcomes were cause-specific mortality and all-cause and cause-specific permanent transfer to hemodialysis. RESULTS: A total of 7,539 PD patients were enrolled between June 2016 and April 2019, with follow-up till December 2020. Patients were divided into two cohorts: TM group (39.1%) and non-TM group (60.9%). A propensity score was used to create 2,160 matched pairs in which the baseline covariates were well-balanced. There were significantly lower risks of all-cause mortality (HR 0.59 [0.51, 0.67], p < 0.001), CVD mortality (HR 0.59 [0.49, 0.70], p < 0.001), all-cause transfer to hemodialysis (0.57 [0.48, 0.67], p < 0.001), transfer to hemodialysis from PD-related infection (0.67 [0.51, 0.88], p = 0.003), severe fluid overload (0.40 [0.30, 0.55], p < 0.001), inadequate solute clearance (0.49 [0.26, 0.92], p = 0.026), and catheter-related noninfectious complications (0.41 [0.17, 0.97], p = 0.041) in the TM group compared with the non-TM group. CONCLUSION: This study indicated real-world associations between TM usage and reduction in patient survival and technique survival through a multicenter prospective cohort.

Molecular Genetics of Anthracnose Resistance in Maize.

Maize (Zea mays), also called corn, is one of the top three staple food crops worldwide and is also utilized as feed (e.g., feed grain and silage) and a source of biofuel (e.g., bioethanol). Maize production is hampered by a myriad of factors, including although not limited to fungal diseases, which reduce grain yield and downgrade kernel quality. One such disease is anthracnose leaf blight and stalk rot (ALB and ASR) caused by the hemibiotrophic fungal pathogen Colletotrichum graminicola. The pathogen deploys a biphasic infection strategy to colonize susceptible maize genotypes, comprising latent (symptomless) biotrophic and destructive (symptomatic) necrotrophic phases. However, the resistant maize genotypes restrict the C. graminicola infection and in planta fungal proliferation during the biotrophic phase of the infection. Some studies on the inheritance of ASR resistance in the populations derived from biparental resistant and susceptible genotypes reveal that anthracnose is likely a gene-for-gene disease in which the resistant maize genotypes and C. graminicola recognize each other by their matching pairs of nucleotide-binding leucine-rich repeat resistance (NLR) proteins (whose coding genes are localized in disease QTL) and effectors (1-2 effectors/NLR) during the biotrophic phase of infection. The Z. mays genome encodes approximately 144 NLRs, two of which, RCg1 and RCg1b, located on chromosome 4, were cloned and functionally validated for their role in ASR resistance. Here, we discuss the genetic architecture of anthracnose resistance in the resistant maize genotypes, i.e., disease QTL and underlying resistance genes. In addition, this review also highlights the disease cycle of C. graminicola and molecular factors (e.g., virulence/pathogenicity factors such as effectors and secondary metabolites) that contribute to the pathogen's virulence on maize. A detailed understanding of molecular genetics underlying the maize-C. graminicola interaction will help devise effective management strategies against ALB and ASR.

First Clinical Study on Long-Acting Growth Hormone Therapy in Children with Turner Sydrome.

Study on long-acting growth hormone (LAGH) therapy in Turner syndrome (TS) is a 2-year retrospective study including patients diagnosed with TS from 2018-2021. Patients were divided into four groups: Group 1 to 4 were low dose (0.1 mg/kg/ w), high-dose (0.2 mg/kg/w) LAGH, daily GH (0.38 mg/kg/w), and untreated control. The efficacy and safety data were analyzed. Seventy-five TS cases with the age 7.9±2.9 years and the bone age 6.8±2.8 years were recruited. In year 1: The change of height standard deviation score (ΔHtSDS) and height velocity (HV) in Group 2 were comparable to Group 3, both two groups were higher than Group 1. ΔHtSDS and HV in all GH treatment group were higher than untreated group. IGF1 increased in all treatment groups, only 4 cases had IGF1>3 SD. In year 2: ΔHtSDS and HV in Group 2 and 3 were comparable. Five cases had IGF1>3 SD. Correlation analysis for LAGH efficacy at year 1 indicated that baseline variables correlated with ΔHtSDS include: GH dose, CA (chronological age), and bone age (BA). The HV was positively correlated with baseline GH dose, HtSDS, IGF-1SDS and negatively correlated with baseline CA, BA, and BMI. No GH-related serious adverse effects were observed. The high-dose LAGH treatment in TS patients is effective and safe as daily GH for 2 years. The favorable prognosis factors include sufficient GH dose and early treatment. IGF1 monitoring and weight control are important.

First Report of Didymella glomerata Causing Didymella Leaf Blight on Maize in China.

Maize (Zea mays L.) is a staple food crop worldwide. In July 2021, gray leaf blight was observed on maize leaves in a field located in Panjin (41°7'11.98" N, 122°4'14.57" E), Liaoning Province, China. Nearly 5% of the maize plants were affected in the field. The leaves of the affected plants showed oval to oblong, gray, sunken lesions with yellow or tan margins. The lesions were scattered all over the leaf surface; however, they were absent on the stalks and other parts of the affected plants. To isolate the pathogen, leaf discs (1.25 mm2) excised from the blight lesions were surface-sterilized with 70% ethanol for 30 seconds, followed by 20% NaOCl for 2 minutes and finally rinsed three times with sterilized water. The discs were cultured on potato dextrose agar (PDA) plates supplemented with streptomycin (100 mg/L) and incubated at 25oC under a 12-h photoperiod for 7 days. Six single spore isolates (two per sampled infected leaf) were purified from the PDA culture plates. The fungal colonies of three selected isolates (one per sampled infected leaf; Pj-1, Pj-2, and Pj-3) were dark brown on the PDA plates and devoid of aerial hyphae; all three isolates grew 11 mm/day on the PDA plates. The number of conidia produced by the isolates on the 6-cm PDA plates 7 days after incubation was ranged from 160 x 108 to 208 x 108 (n = 36). Conidia were hyaline, single-celled and ellipsoidal (3.35-3.56 µm [width] x 6.47-6.70 [length] µm; n = 36). To identify the pathogen, four loci, i.e., 28S subunit (large subunit [LSU]) of the nuclear ribosomal (nr) DNA, internal transcribed spacer (ITS) region (ITS1, 5.8S subunit of nrDNA, and ITS2), the second-largest subunit of RNA polymerase II (rpb2) and ß-tubulin (tub2) were amplified using the primer sets described in the study by Chen el al. 2015. BLASTn search against GenBank revealed that the four amplicon sequences originating from Pj-1, Pj-2, and Pj-3 showed 99-100% homology to the type strain CBS 528.66 of D. glomerata. A phylogenetic tree deduced from a maximum likelihood analysis of a concatenated MUSCLE-based alignment of LSU, ITS region, rpb2, and tub2 sequences of 12 isolates/strains showed that the Pj isolates clustered together with CBS 528.66, along with other D. glomerata isolates/strains, with a high bootstrap support value (i.e., 99). Based on both morphological characteristics and molecular phylogeny, Pj-1, Pj-2, and Pj-3 were identified as the D. glomerata isolates. Since the amplicon sequences of the three isolates were identical, only Pj-2 sequences were deposited in GenBank with accession numbers OM372474 (LSU), OK485138 (ITS), OM406188 (rpb2), and OK485135 (tub2). To confirm pathogenicity, 14-day-old plants (V3 growth stage) of a maize cultivar P178 were spray-inoculated with the Pj-2 conidia (1 x 107 conidia/mL) in a growth chamber. The inoculated leaves exhibited typical gray leaf blight lesions (similar to those detected in the maize field) 7 days post-inoculation at 25oC and 95-100% humidity under a 12-h photoperiod, whereas the leaves spray-inoculated with sterilized water remained healthy. The pathogenicity assay was repeated three times; the pathogen was re-isolated from the inoculated leaves each time and confirmed by the morphological characteristics and the molecular phylogeny based on the four loci to be D. glomerata, fulfilling Koch's postulates. This first report of D. glomerata causing Didymella leaf blight on maize will help develop robust disease management strategies against this emerging fungal pathogen.

The Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study: Design and methods.

OBJECTIVES: The primary objective of the Peritoneal Dialysis Telemedicine-assisted Platform Cohort (PDTAP) Study is to explore potential predictors and their effects on patient survival, technique survival, and the occurrence of infectious and noninfectious complications. DESIGN: The PDTAP study is a national-level cohort study in China. A newly developed PD telemedicine application provided a unique and convenient way to collect multicenter, structured data across units. SETTING: The PDTAP study was underway in 27 hospitals from 14 provinces located at 7 geographical regions (northwest, northeast, north, central, southwest, southeast, and south) in China. PARTICIPANTS: Our study aims to enroll at least 7000 adult patients with end-stage renal disease receiving PD. METHODS: Approval has been obtained through the ethics committees of all hospitals. All participants signed the informed consent form after the center had received ethics board approval in accordance with the Declaration of Helsinki. MAIN OUTCOME MEASURES: Patient survival, technique survival, hospitalization, and the occurrence of infectious and noninfectious complications. CONCLUSIONS: The PDTAP study aims to explore potential predictors and their effects on patient survival, technique survival, and infectious and noninfectious complications using a newly developed PD telemedicine system to collect multicenter, structured data in real-world practice. Substantial and transformable findings in relation to PD practices were expected. This study also developed a national-level infrastructure for further collaboration and ancillary investigation.

Combination of Developmental Behaviors and Transcriptome Reveals Differential Response Mechanisms of Phytophthora sojae to Aspartic Acid and Glucose in Seed Exudates.

Isoflavones in soybean seed and root exudates are host-specific signal molecules for Phytophthora sojae to recognize host soybean. G protein and calcium signaling pathway are involved in the chemotaxis of zoospores in the recognition of isoflavones. To investigate the role of host nonspecific signaling molecules (sugars and amino acids) in seed and root exudates in zoospore chemotaxis and mycelial growth, the transcriptome of P. sojae responding to aspartic acid (Asp) and glucose (Glc) was analyzed by the RNA-seq method. We found that the relative in situ concentrations of amino acids and sugars significantly promoted zoospore chemotaxis, as do isoflavones. Transcriptomics showed that both similarity and difference existed in response mechanisms of P. sojae to Asp and Glc. Asp and Glc activated mitogen-activated protein kinase signaling pathway and phosphatidylinositol signaling system but not G-protein signaling pathway, which have been reported to be responsible for zoospore chemotaxis. In addition, ubiquitin-mediated proteolysis and ATP binding cassette transporters were also activated by Asp and Glc. Meanwhile, glutathione signaling pathway uniquely participated in the response of P. sojae to Asp but not involved in the response process to Glc, which is waiting for further study. Our results provide new insights into the molecular mechanism of zoospore response to Asp and Glc.

Comparison of gut microbiota in autism spectrum disorders and neurotypical boys in China: A case-control study.

BACKGROUND: Autism spectrum disorders (ASDs) are a set of complex neurobiological disorders. Growing evidence has shown that the microbiota that resides in the gut can modulate brain development via the gut-brain axis. However, direct clinical evidence of the role of the microbiota-gut-brain axis in ASD is relatively limited. METHODS: A case-control study of 71 boys with ASD and 18 neurotypical controls was conducted at China-Japan Friendship Hospital. Demographic information and fecal samples were collected, and the gut microbiome was evaluated and compared by 16S ribosomal RNA gene sequencing and metagenomic sequencing. RESULTS: A higher abundance of operational taxonomic units (OTUs) based on fecal bacterial profiling was observed in the ASD group. Significantly different microbiome profiles were observed between the two groups. At the genus level, we observed a decrease in the relative abundance of Escherichia, Shigella, Veillonella, Akkermansia, Provindencia, Dialister, Bifidobacterium, Streptococcus, Ruminococcaceae UCG_002, Megasphaera, Eubacterium_coprostanol, Citrobacter, Ruminiclostridium_5, and Ruminiclostridium_6 in the ASD cohort, while Eisenbergiella, Klebsiella, Faecalibacterium, and Blautia were significantly increased. Ten bacterial strains were selected for clinical discrimination between those with ASD and the neurotypical controls. The highest AUC value of the model was 0.947. CONCLUSION: Significant differences were observed in the composition of the gut microbiome between boys with ASD and neurotypical controls. These findings contribute to the knowledge of the alteration of the gut microbiome in ASD patients, which opens the possibility for early identification of this disease.

Theoretical Insights into the Cotransport Mechanism of GSH with Anticancer Drugs by MRP1.

The multidrug resistance protein MRP1 is an ATP binding cassette (ABC) transporter that confers resistance to many anticancer drugs and regulates redox homeostasis, inflammation, and hormone secretion. MRP1 actively transports compounds across cell membranes, and the presence of glutathione (GSH) is required in many cases. However, the process of MRP1-mediated substrate transportation has been poorly understood. With extensive molecular dynamics simulations, we have found a sandwich-like structure which is generated by GSH, a transmembrane α-helices 11 (TM11)-TM17 axis, and anticancer drugs. This structure is crucial in MRP1 transportation. It triggers the motion of TM11 and TM17, followed by the movement of nucleotide-binding domains 1 (NBD1) and 2 (NBD2), and finally an occluded structure is formed. Trp1246, Lys332, and Phe594 were identified as the main contributors in the formation of the sandwich-like structure. Our findings clearly explain the synergy of GSH with an anticancer drug in MRP1 transportation and have significant meanings for the rational design of novel inhibitors against MRP1.

Fragment-centric topographic mapping method guides the understanding of ABCG2-inhibitor interactions.

Understanding protein-ligand interactions is crucial to drug discovery and design. However, it would be extremely difficult for the proteins which only have one available apo structure but multiple binding sites. To address this constraint, a fragment-centric topographic mapping method (AlphaSpace software) was employed to map out concave interaction pockets at the assigned protein region. These pockets are used as complementary spaces to screen the known inhibitors for this specific binding site and to guide the molecular docking pose selection as well as protein-ligand interaction analysis. By mapping the shape of central cavity surface, we have tested the strategy against a multi-drug resistant transmembrane protein-ABCG2 to assist in generating a pharmacophore model for its inhibitors that is based on the structure of apo. Classical molecular simulation and accelerated molecular simulation are used to verify the accuracy of inhibitor screening and binding pose selection. Our study not only has gained insight for the development of novel specific ABCG2 inhibitors, but also has provided a general strategy in describing protein-ligand interactions.

[Correlation between long time systolic blood pressure variability and short time systolic blood pressure in aged population].

OBJECTIVE: To investigate the correlation between long time systolic blood pressure variability(SBPV)and short time SBPV in aged population. METHODS: A total of 752 subjects aged ≥60 years of Kailuan Group who took part in 2006-2007, 2008-2009, 2010-2011 and 2012-2013 health examination were included by cluster sampling method.Long time SBPV was calculated by standard deviation of mean systolic blood pressure measured in 2006-2007, 2008-2009, 2010-2011 and 2012-2013, standard deviation represents short time systolic blood pressure which is derived from 24 hour ambulatory blood pressure monitoring. The observation population was divided into three groups according to the third tertiles of the time systolic blood pressure variability: the first point(<9.09 mmHg (1 mmHg=0.133 kPa)), second point (≥9.09 mmHg, and <14.29 mmHg), and third point (≥14.29 mmHg). Multivariate logistic regression analysis was used to analyze the correlation between long time systolic blood pressure variability and short time systolic blood pressure. RESULTS: (1) The participants' age were (67.0±5.7) years old (284 women). (2) The 24 hours and daytime SSD were (14.7±4.0) mmHg, (14.7±3.5) mmHg, (15.7±4.4) mmHg (P=0.010) and (14.1±4.4) mmHg, (14.2±3.5) mmHg and (15.4±4.6) mmHg (P<0.001) according to the tertiles of long time systolic blood pressure variability, respectively, nighttime SSD were (12.0±4.4) mmHg, (11.8±4.8) mmHg and (11.9±4.9) mmHg (P=0.900). (3) Multiple logistic regression analysis showed that the tertiles of long time SSD was the risk factor for increasing daytime SSD>14.00 mmHg (OR=1.51, 95%CI: 1.03-2.23, P=0.037), but not a risk factor for increasing 24 hours SSD>14.41 mmHg (OR=1.10, 95%CI: 0.75-1.61, P=0.639) and nighttime SSD>11.11 mmHg (OR=0.98, 95%CI: 0.67-1.42, P=0.899). CONCLUSION: Increased long time SBPV is a risk factor for increasing daytime SBPV.

An adoptive T cell immunotherapy targeting cancer stem cells in a colon cancer model.

PURPOSE: Colon cancer is one of the most common malignancies worldwide. Cancer stem-like cells (CSCs) are a distinct subgroup of cancer cells that play a vital role in the development of cancer and also a role in the development of resistance against therapeutic agents. In this study we investigated the role of CSCs in colon cancer and evaluated the tumor-associated antigen CEP55 for targeting immunotherapeutically CSCs. METHODS: Side population (SP) cells from colon cancer cell line SW480, were isolated using DNA-binding dye Hoechst 33342. The cytotoxic activity of cytotoxic T lymphocytes (CTL) clone 41 for side population (SP) cells and main population (MP) cells was evaluated using 51Cr release assay. The SP cells, MP cells and presorted cells from the colon cancer cell line were evaluated in NOD/SCID mice. RESULTS: The isolated SP cells showed resistance to the chemotherapeutic agents irinotecan and oxaliplatin, which suggests that targeting the CSCs can be a better strategy for the treatment of chemotherapy-resistant colon cancer. HLA class I and HLA-A24 in SP cells and MP cells were expressed at the same level. We used CTL clone 41 to corroborate the sensitivity of SP cells to cytotoxic T lymphocyte response. The cytotoxic responses of SP cells were to the same extent as they were in MP cells and pre-sorted cells. Adoptive transfer of CTL clone 41 in immunodeficient mice inhibited SW480-induced tumors, suggesting that this approach can be used for colon cancer immunotherapy. CONCLUSION: Our novel findings suggest that colon cancer CSCs are sensitive to CTLs, and CEP55, a tumor-associated antigen, can be successfully used as active immunotherapy for targeting CSCs in colon cancer.

[Impact of resting heart rate on the progression to hypertension in prehypertension patients].

OBJECTIVE: To observe the effect of resting heart rate (RHR) on the progression to hypertension in patients with prehypertension. METHODS: People who participated the physical examination between 2006 and 2007 at Kailuan medical group and diagnosed as prehypentension were selected as the observation cohort. The second and the third physical examination were conducted between 2008 and 2009 and between 2010 and 2011. The observation population was divided into five groups according to the different levels of RHR at baseline: the first group ( ≤69 beats/min), the second group (70-74 beats/min), the third group (75-79 beats/min), the fourth group (80-84 beats/min) and the fifth group ( ≥85 beats/min). The rate of the progression to hypertension was compared among five groups, and the relationship between RHR and the progression to hypertension was estimated using Cox proportional hazard analysis. RESULTS: A total of 34 512 patients with prehypentension were recruited and 25 392 patients were involved in the final statistics after excluding patients who died or were lost to follow-up. A total of 13 228 (52.1%) patients with prehypentension developed hypertension during follow-up. The rate of the progression to hypertension increased with the RHR (first group: 51.2%, second group: 50.1%, third group: 52.9%, fourth group: 53.5%, fifth group: 57.5%). Multiple Cox regression models showed that the risk of the progression to hypertension increased with the RHR levels. Patients in the fifth group carried 1.25 times higher risk for developing hypertension than patients in the second group after adjustment for age, gender, systolic blood pressure, diastolic blood pressure, waist circumference, body mass index, triglyceride, total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, fasting blood glucose, serum uric acid, C-reactive protein, smoking, drinking, physical exercise and family history of hypertension at baseline. CONCLUSION: Elevated RHR is an independent risk factor for the progression to hypertension in patients with prehypertension.