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Previous studies demonstrated that metformin has obvious antiatherogenic properties, but the exact mechanism remains unclear. Therefore, we established an atherosclerotic rabbit model in order to investigate the potential effects of metformin on transcription factor nuclear factor κB (NF-κB) and serum high-sensitivity C-reactive protein (hs-CRP) level, which had been regarded as proatherogenic factors. New Zealand rabbits were randomly divided into three groups: a control group ( n = 8), an atherosclerotic group (AS group, n = 8), and a metformin treatment group (Met group, n = 8). The experimental atherosclerotic rabbit model was successfully established at the end of the 8th week. From the 9th week, rabbits in the Met group were administered with 150 mg/kg metformin daily by gavage. Blood samples were collected at days 0 and 8, and at 16 weeks to detect the level of blood lipid and serum glucose. At the end of the experiment, blood samples were withdrawn for determining serum hs-CRP. Aortic samples were harvested for histomorphometric analysis. Immunohistochemistry and Western blotting were used to detect the expression of NF-κB subunit p65 in nuclear extracts and phosphorylation of inhibitor of nuclear factor κB (IκB) in cytoplasmic extracts. An experimental atherosclerotic rabbit model was successfully established. The expression of nuclear NF-κB subunit p65 and cytoplasmic phosphorylation of IκB protein in the vessel wall was enhanced ( P < 0.01, respectively) in the AS group, and serum hs-CRP level was significantly increased in the AS group compared with the control group (3.90 ± 0.25 mg/l versus 1.36 ± 0.14 mg/l, P < 0.01). Treatment with metformin significantly attenuated the progression of aortic atherosclerosis. In the Met group, there was a marked reduction in nuclear NF-κB subunit p65 and cytoplasmic phosphorylation of IκB protein expression ( P < 0.01). Serum hs-CRP concentration was also significantly decreased (3.20 ± 0.20 mg/l versus 3.90 ± 0.25 mg/l, P < 0.05). Metformin inhibits the phosphorylation of IκB and the activation of NF-κB in the vessel wall of experimental atherogenesis of rabbits, as well as decreasing the serum level of hs-CRP, thus suggesting that metformin has vascular anti-inflammatory properties, which may be one of its antiatherogenic mechanisms. [ABSTRACT FROM AUTHOR]

Objective:. Previous studies have shown increased expression of nitric oxide synthase 2 (NOS2) in rat heart several weeks after myocardial infarction (MI). The aim of this study was to examine the effect of chronic administration of S-methylisothurea (SMT), a selective NOS2 inhibitor, commenced one week after MI on hemodynamic parameters and left ventricular (LV) remodeling in rats. Methods:. Rats with MI induced by left coronary ligation were given SMT (0.5 mg/kg/d) or saline by gavage starting one week after MI. After chronic administration for five weeks, hemodynamic and cardiac morphologic studies were performed, and lung water content, plasma NOx concentration, NOS2 protein level, myocyte size and collagen volume fraction of noninfarct LV area were quantified. Results:. The NOx concentration in plasma and the NOS2 protein level in noninfarct myocardium in MI rats were higher than controls. When compared with the MI rats receiving saline, chronic administration of SMT reduced myocyte size (15.1 ± 1.6 µm vs 16.9 ± 2.3 µm, P < 0.05), collagen volume fraction of noninfarct LV area (4.4% ± 1.1% vs 5.7% ± 1.2%, P < 0.01) and lung water content (77.4% ± 1.4% vs 79.3% ± 0.9%, P < 0.01), without affecting infarct size. Administration of SMT had no significant effect on heart rate and mean arterial pressure, but decreased LV end-diastolic pressure (8.7 ± 2.1 mmHg vs 13.4 ± 3.1 mmHg, P < 0.01), central venous pressure (0.9 ± 0.3 mmHg vs 1.5 ± 0.5 mmHg, P < 0.01) and inner LV diameter (6.9 ± 0.3 mm vs 7.2 ± 0.3 mm, P < 0.05) in the MI rats. Plasma level of NOx in the MI rats receiving SMT was reduced to control level. Conclusions:. Chronic administration of SMT had beneficial effects on LV remodeling and cardiac dysfunction in MI rats, suggesting the possibility that inhibition of NOS2 could be a therapeutic tool for cardiac dysfunction after MI. [ABSTRACT FROM AUTHOR]

Objective: To investigate the distribution of H. pylori antigens in the gastric mucosa in patients with H. pylori infection, and the relationship between the distribution and gastric cancer. Methods: Of 112 patients confirmed by pathological study to have chronic superficial gastritis, precancerous changes (chronic atrophic gastritis, intestinal metaplasia or atypical hyperplasia) and gastric cancer, 28 were H. pylori negative and 84 were H. pylori positive. H. pylori antigens in the gastric mucosa were detected by immunohistochemistry. Results: The H. pylori positive group, comprised 12 of 22 (50.0%) in the chronic superficial gastritis group, 22 of 25 (88.0%) in the precancerous changes group and 13 of 35 (37.1%) in the gastric cancer group. The positive rates of H. pylori antigens in the cytoplasm progressively increased, respectively at 0.0% (0/12), 63.6% (14/22) and 84.6% (11/13) for the same groups ( χ 2=19.76, P=0.000); H. pylori antigens were located in the mucus layer and above the neck of the mucosal gland in 9 of 12 (75.0%) cases with chronic superficial gastritis, at the neck of the mucosal gland and the isthmus in 12 of 22 (54.5%) cases with precancerous changes, below the isthmus in 9 of 13 (69.2%) cases with gastric cancer ( χ 2=25.30, P=0.000). In the H. pylori negative group, no H. pylori antigen was observed. Conclusion: With the progression of chronic superficial gastritis→precancerous changes→gastric cancer, H. pylori antigens progressively migrated from the outer part to the inner part of the cell, and from the superficial to the deep gastric mucosa. [ABSTRACT FROM AUTHOR]

Abstract Calcium (Ca) is an essential mineral nutrient and plays a crucial signaling role in all living organisms. Increasing Ca content in staple foods such as rice is vital for improving Ca nutrition of humans. Here we map a quantitative trait locus that controls Ca concentration in rice grains and identify the causal gene as GCSC1 (Grain Ca and Sr Concentrations 1), which encodes a chloroplast vesicle localized homo-oligomeric protein. GCSC1 exhibits Ca2+ transport activity in heterologous assays in yeast and Xenopus laevis oocytes and is involved in the efflux of Ca2+ from the chloroplast to the cytosol. Knockout of GCSC1 results in increased chloroplast Ca concentration, lower stomatal conductance in leaves and enhanced Ca allocation to grains. Natural variation in grain Ca concentration is attributed to the variable expression of GCSC1 resulting from its promoter sequence variation. Our study identifies a chloroplast localized heavy metal-associated domain containing protein that regulates chloroplast Ca2+ efflux and provides a way to biofortify Ca in rice to benefit human nutrition.

Pigeon coccidiosis caused by Eimeria spp. is an important veterinary disease with a significant economic impact on the pigeon industry. Preventive measures for Eimeria columbarum in pigeons have been hampered by the lack of extensive genetic, morphological, and biological data on the oocysts. In this study, we examined the prevalence and identity of Eimeria spp. in domestic pigeons from seven cities in Guangdong Province, China. Data show that coccidiosis was prevalent in domestic pigeons in Guangdong Province, with an overall Eimeria spp. detection rate of 73.4%. Five Eimeria species were identified, including E. columbarum (73.4%), Eimeria kapotei (25.6%), Eimeria labbeana (19.6%), Eimeria duculai (19.6%), and Eimeria tropicalis (6.7%). We obtained single oocyst-derived lines of the dominant E. columbarum from fecal specimens. E. columbarum oocysts measured 20.06 ± 0.69 μm × 18.63 ± 1.03 μm, and sporocysts measured 10.29 ± 0.82 μm × 85.38 ± 0.46 μm. In infection experiment using obtained E. columbarum isolates, 60-day-old coccidia-free pigeons exhibited a prepatent period of 105 h and patent period of 9–10 days followed by severe diarrhea, depression, anorexia, and emaciation. Endogenous development of the parasite was observed mainly in the cytoplasm of epithelial cells in the duodenum, jejunum, ileum, and rectum. Two generations of meronts developed on days 3 and 4 after infection, respectively, while gamont and gamete developed on day 5 after infection. The morphological, genetic, and biological data are expected to be useful in elucidating the biological characterization of pigeon coccidiosis to develop measures against the treatment and containment of this disease.

Plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) within the human and animal intestine represents a substantial global health concern. linoleic acid (LA) has shown promise in inhibiting conjugation in vitro, but its in vivo effectiveness in the mammalian intestinal tract is constrained by challenges in efficiently reaching the target site. Recent advancements have led to the development of waterborne polyurethane nanoparticles for improved drug delivery. In this study, we synthesized four waterborne polyurethane nanoparticles incorporating LA (WPU@LA) using primary raw materials, including N-methyldiethanolamine, 2,2'-(piperazine-1,4-diyl) diethanol, isophorone diisocyanate, castor oil, and acetic acid. These nanoparticles, identified as WPU0.89@LA, WPU0.99@LA, WPU1.09@LA, and WPU1.19@LA, underwent assessment for their pH-responsive release property and biocompatibility. Among these, WPU0.99@LA displayed superior pH-responsive release properties and biocompatibility towards Caco-2 and IPEC-J2 cells. In a mouse model, a dosage of 10 mg/kg/day WPU0.99@LA effectively reduced the conjugation of IncX4 plasmids carrying the mobile colistin resistance gene (mcr-1) by more than 45.1-fold. In vivo toxicity assessment demonstrated that 10 mg/kg/day WPU0.99@LA maintains desirable biosafety and effectively preserves gut microbiota homeostasis. In conclusion, our study provides crucial proof-of-concept support, demonstrating that WPU0.99@LA holds significant potential in controlling the spread of antibiotic resistance within the mammalian intestine.

ABSTRACT Mycophenolate mofetil (MMF) is commonly utilized for the treatment of neuromyelitis optica spectrum disorders (NMOSD). However, a subset of patients experience significant gastrointestinal (GI) adverse effects following MMF administration. The present study aims to elucidate the underlying mechanisms of MMF-induced GI toxicity in NMOSD. Utilizing a vancomycin-treated mouse model, we compiled a comprehensive data set to investigate the microbiome and metabolome in the GI tract to elucidate the mechanisms of MMF GI toxicity. Furthermore, we enrolled 17 female NMOSD patients receiving MMF, who were stratified into non-diarrhea NMOSD and diarrhea NMOSD (DNM) groups, in addition to 12 healthy controls. The gut microbiota of stool samples was analyzed using 16S rRNA gene sequencing. Vancomycin administration prevented weight loss and tissue injury caused by MMF, affecting colon metabolomes and microbiomes. Bacterial β-glucuronidase from Bacteroidetes and Firmicutes was linked to intestinal tissue damage. The DNM group showed higher alpha diversity and increased levels of Firmicutes and Proteobacteria. The β-glucuronidase produced by Firmicutes may be important in causing gastrointestinal side effects from MMF in NMOSD treatment, providing useful information for future research on MMF.IMPORTANCENeuromyelitis optica spectrum disorder (NMOSD) patients frequently endure severe consequences like paralysis and blindness. Mycophenolate mofetil (MMF) effectively addresses these issues, but its usage is hindered by gastrointestinal (GI) complications. Through uncovering the intricate interplay among MMF, gut microbiota, and metabolic pathways, this study identifies specific gut bacteria responsible for metabolizing MMF into a potentially harmful form, thus contributing to GI side effects. These findings not only deepen our comprehension of MMF toxicity but also propose potential strategies, such as inhibiting these bacteria, to mitigate these adverse effects. This insight holds broader implications for minimizing complications in NMOSD patients undergoing MMF therapy.

Objective: We aimed to explore the geographic differences in psychological symptoms, sleep quality, and quality of life (QoL) among adult patients with inflammatory bowel disease (IBD). Methods: A unified questionnaire was developed to collect data on psychological status and QoL of IBD patients from 42 hospitals across 22 provinces, municipalities, and autonomous regions in China's mainland from September 2021 to May 2022. Results: A total of 2478 patients with IBD were surveyed. The proportions of patients with anxiety (28.5% vs 23.1%), depression (32.3% vs 27.8%), and poor QoL (44.8% vs 32.2%) were significantly higher in patients from the northern region compared to the southern region (all P < 0.05). In the western region, the proportions of patients with anxiety (31.9% vs 23.0%), depression (37.7% vs 26.7%), sleep disturbances (64.5% vs 58.5%), and poor QoL (44.9% vs 34.8%) were significantly higher than in the eastern and central regions (all P < 0.01). Patients from inland regions had significantly higher rates of anxiety (27.1% vs 23.3%), depression (32.5% vs 26.0%), sleep disturbance (62.0% vs 57.7%), and poor QoL (43.5% vs 29.9%) compared to those from coastal regions (all P < 0.05). In economically underdeveloped areas, the proportions of patients with depression (33.1% vs 28.5%) and poor QoL (52.0% vs 32.4%) were significantly higher than in economically (relatively) developed areas (both P < 0.05). Conclusion: There are significant geographic differences in psychological symptoms, sleep quality, and QoL among Chinese patients with IBD, which might provide valuable insights for global IBD research and clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Although customized three-dimensional (3D) templates have shown advantages in brachytherapy, widespread application is still full of challenges. The present work proposed the use of a commercial 3D standardized template-guided intracavitary/interstitial brachytherapy (IC/ISBT) that could provide simple and reproducible needles' insertion. Material and methods: 43 patients received external beam radiotherapy (EBRT) with 45-50.4 Gy and subsequent IC/ISBT with 28 Gy in 4 fractions. In terms of IC/ISBT, 24 patients were treated with 3D standardized templates (ST group), and 19 patients were treated using free-hand implantation (FH group). Consistency of implantation for all needles and dosimetric differences for target and organs at risk (OARs) were then compared between two groups. Results: The mean variation of tip position between insertions for needles was 1.41 mm and 2.74 mm in ST group and FH group, respectively (p < 0.001). ST group was superior in terms of dosimetric conformity index (CI) and D90 for high-risk clinical target volume (HR-CTV), significantly improving to 23.21% (p < 0.001) and 3.58% (p = 0.031) compared with FH group. The D2cc of the bladder and sigmoid in the ST group were lower than those in the FH group (p < 0.05). Meanwhile, a strong correlation between the volume of HR-CTV and its CI in the ST group (R = 0.865, p < 0.001) was found with Spearman's correlation analysis. Conclusions: The implementation of 3D standardized template can potentially improve the precision and consistency in the needle insertion procedure that may replace some customized 3D templates, and achieve clinical satisfied dose distribution in IC/ISBT plans for patients with LACC. [ABSTRACT FROM AUTHOR]

Abstract Objectives To evaluate the performance of a dual-energy computed tomography (DECT) virtual non-calcium (VNCa) technique in the detection of edema-like marrow signal intensity (ELMSI) in patients with knee joint osteoarthritis (OA) compared to magnetic resonance imaging (MRI). Methods The study received local ethics board approval, and written informed consent was obtained. DECT and MRI were used to examine 28 knees in 24 patients with OA. VNCa images were generated by dual-energy subtraction of calcium. The knee joint was divided into 15 regions for ELMSI grading, performed independently by two musculoskeletal radiologists, with MRI as the reference standard. We also analyzed CT numbers through receiver operating characteristics and calculated cut-off values. Results For the qualitative analysis, we obtained CT sensitivity (Readers 1, 2 = 83.7%, 89.8%), specificity (Readers 1, 2 = 99.5%, 99.5%), positive predictive value (Readers 1, 2 = 95.3%, 95.7%), and negative predictive value (Readers 1, 2 = 97.9%, 98.7%) for ELMSI. The interobserver agreement was excellent (κ = 0.92). The area under the curve for Reader 1 and Reader 2 was 0.961 (95% CI 0.93, 0.99) and 0.992 (95% CI 0.98, 1.00), respectively. CT numbers obtained from the VNCa images were significantly different between regions with and without ELMSI (p

Purpose: The purpose of this study was to investigate the precision of deep learning (DL)-based auto-reconstruction in localizing interstitial needles in post-operative cervical cancer brachytherapy (BT) using three-dimensional (3D) computed tomography (CT) images. Material and methods: A convolutional neural network (CNN) was developed and presented for automatic reconstruction of interstitial needles. Data of 70 post-operative cervical cancer patients who received CT-based BT were used to train and test this DL model. All patients were treated with three metallic needles. Dice similarity coefficient (DSC), 95% Hausdorff distance (95% HD), and Jaccard coefficient (JC) were applied to evaluate the geometric accuracy of auto-reconstruction for each needle. Dose-volume indexes (DVI) between manual and automatic methods were used to analyze the dosimetric difference. Correlation between geometric metrics and dosimetric difference was evaluated using Spearman correlation analysis. Results: The mean DSC values of DL-based model were 0.88, 0.89, and 0.90 for three metallic needles. Wilcoxon signed-rank test indicated no significant dosimetric differences in all BT planning structures between manual and automatic reconstruction methods (p > 0.05). Spearman correlation analysis demonstrated weak link between geometric metrics and dosimetry differences. Conclusions: DL-based reconstruction method can be used to precisely localize the interstitial needles in 3D-CT images. The proposed automatic approach could improve the consistency of treatment planning for post-operative cervical cancer brachytherapy. [ABSTRACT FROM AUTHOR]

The resistance to dieldrin gene (RDL) encodes the primary subunit of the insect ionotropic γ‐aminobutyric acid (GABA) receptor (GABAR), which is the target of phenylpyrazole and isoxazoline insecticides. The splice variants in exons 3 and 6 of RDL, which have been widely explored in many insects, modulate the agonist potency of the homomeric RDL GABAR and potentially play an important role in the development of insects. In the present study, four splice variants of exon 9 were identified in RDL of the small brown planthopper, Laodelphax striatellus (LsRDL), resulting in LsRDL‐9a, LsRDL‐9a', LsRDL‐9b, and LsRDL‐9c. LsRDL‐9a has one more amino acid (E, glutamic acid) compared with LsRDL‐9a', and LsRDL‐9b lacked two amino acids and had seven different amino acids compared with LsRDL‐9c. Two‐electrode voltage‐clamp recording on LsRDLs expressed in Xenopus oocytes showed that alternative splicing of exon 9 has significant impact on LsRDL sensitivity to the agonists GABA and β‐alanine, whereas no significant difference was observed in the potencies of the non‐competitive antagonists (NCAs) ethiprole and fluralaner on the splice variants. Our results suggest that alternative splicing of RDL exon 9 broadens functional capabilities of the GABAR in L. striatellus by influencing the action of GABA. [ABSTRACT FROM AUTHOR]

Abstract Purpose: To seek optimal keV settings for imaging carpal tunnel in adults by dual-energy computed tomography (DECT) monoenergetic technique; to describe anatomic characteristics of carpal tunnel and to observe correlation between carpal bony and soft tissue structures. Methods: DECT images of 20 wrists (11 left and 9 right wrists; 14 men, mean age 26.93 ± 1.38 years, range 23 to 28, and 6 women, mean age 24.17 ± 0.98 years, range 23 to 26) were evaluated. Monoenergetic images were reconstructed at 42, 62, 82, 102, 122, and 142 keV. Image quality was assessed along a 5-point Likert scale, and the highest-quality images were chosen for quantitative analysis. Two musculoskeletal radiologists performed both analyses independently. Results: The optimal energy spectrum with the best contrast-to-noise ratio (CNR) for monoenergetic images were at 62 keV (19 wrists, 95%) and 61 keV (1 wrist, 5%). There was substantial interobserver agreement between the readers in the 5-point Likert scale analysis of image quality (? = 0.793). Bland-Altman plots also indicated good agreement between observers in quantitative analysis. Intra-category 1 and 2 correlation was mostly discovered at hamate hook level and middle level of pisiform (P < 0.05), while bony and soft tissue structures partly reached correlation (P < 0.05). Conclusion: The optimal energy spectrum for monoenergetic DECT imaging of carpal tunnel structures was 62 keV. DECT monoenergetic imaging could predict changes in soft tissue structures and demonstrate carpal tunnel anatomic structures. Keywords: DECT, monoenergetic, keV, carpal tunnel, Continuous...

• Broflanilide shows low toxicity to zebrafish (Danio rerio). • Both CYP450 and GST significantly contribute to the detoxification of broflanilide. • Long-term exposure to broflanilide could lead high bioconcentration risks in D. rerio. Broflanilide, a novel meta-diamide insecticide, shows high insecticidal activity against agricultural pests and is scheduled to be launched onto the market in 2020. However, little information about its potential toxicological effects on fish has been reported. In this study, broflanilide showed low toxicity to the zebrafish, Danio rerio , with LC 50 > 10 mg L−1 at 96 h and also did not inhibit GABA-induced currents of the heteromeric Drα1β2Sγ2 GABA receptor. Broflanilide showed medium bioconcentration level with a bioconcentration factor at steady state (BCF ss) of 10.02 and 69.40 in D. rerio at 2.00 mg L−1 and 0.20 mg L−1, respectively. In the elimination process, the concentration of broflanilide rapidly decreased within two days and slowly dropped below the limit of quantification after ten days. In the 2.00 mg L-1 broflanilide treatment, CYP450 activity was significantly increased up to 3.11-fold during eight days. Glutathione- S - transferase (GST) activity significantly increased by 91.44 % within four days. In conclusion, the acute toxicity of broflanilide was low, but it might induce chronic toxicity, affecting metabolism. To our knowledge, this is the first report of the toxicological effects of broflanilide on an aquatic organism, which has the potential to guide the use of broflanilide in the field. [ABSTRACT FROM AUTHOR]

• Six target compounds were designed, synthesized and evaluated. • These compounds showed multifunctional activity in vitro. • T5 displayed hypoglycemic and supplement of NO in vivo. Both nitric oxide (NO) dysfunction and oxidative stress have been regarded as the important factors in the development and progression of diabetes and its complications. Multifunctional compounds with hypoglycemic, NO supplementation and anti-oxidation will be the promising agents for treatment of diabetes. In this study, six phenylfuroxan nitric oxide (NO) donor phenols were synthesized, which were designed via a combination approach with phenylfuroxan NO-donor and natural phenols. These novel synthetic compounds were screened in vitro for α-glucosidase inhibition, NO releasing, anti-oxidation, anti-glycation and anti-platelet aggregation activity as well as vasodilatation effects. The results exhibited that compound T5 displayed more excellent activity than other compounds. Moreover, T5 demonstrated significant hypoglycemic activity in diabetic mice and oral glucose tolerance test (OGTT) mice. T5 also showed NO releasing and anti-oxidation in diabetic mice. Based on these results, compound T5 deserves further study as potential new multifunctional anti-diabetic agent with antioxidant, NO releasing, anti-platelet aggregation and vasodilatation properties. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Design of 5-(4-hydroxyphenyl)-3 H -1,2-dithiole-3-thione derivatives with a significantly hypolipidemic activity. • Study indicated that tested compound also showed hepatoprotective activity in hyperlipidaemia. • The tested compound displayed potent antioxidant and anti-inflammatory activities. Abstract Hypolipidemic effects of the newly synthesized 5-(4-hydroxyphenyl)-3 H -1,2-dithiole-3-thione-based fibrates were evaluated in Triton WR-1339 and high-fat diet (HFD)-induced hyperlipidemic mice. Preliminary screening of all the synthesized compounds was done by using an acute model (Triton WR-1339 model), in which compound 6 shown more significant antidyslipidemic activity than fenofibrate (FF). The compound 6 was also found to reduce serum triglyceride (TG), total cholesterol (TC) and low density lipoprotein cholesterin (LDL) in HFD-induced hyperlipidemic mice. Moreover, compound 6 displayed hepatoprotective effect, a significant amelioration in hepatic indices (AST and ALT) toxicity was observed and the histological examination showed that compound 6 inhibited the development of hepatic lipid accumulation and ameliorated the damage in hepatic tissue compared to model mice. Additional effects such as the potent antioxidant and anti-inflammatory action confirmed and reinforced the efficacy of compound 6 as a new agent of dual-effect hypolipidemic and hepatoprotective activities. [ABSTRACT FROM AUTHOR]

Oxidative stress has been regarded as the leading mechanism of the hepatotoxicity of clofibrate ( CF ). To achieve multifunctional novel hypolipidemic agents with hypolipidemia, antioxidant, and ameliorating liver injury, clofibric acid derivative hydroxytyrosol-clofibrate ( CF-HT ) was synthesized by molecular hybridization. CF-HT exhibited significant hypolipidemia, reducing serum triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 30%, 33%, and 29% in hyperlipidemic mice induced by Triton W R 1339. CF-HT also shown hepatoprotective effect, a significant decrease in hepatic indices toxicity was observed, i.e. aspartate and lactate transaminases (AST and ALT) activities, alkalines phosphatases (ALP), and total bilirubin (TBIL) levels. The liver weight and liver coefficient were also ameliorated. Serum superoxide dismutase (SOD) was significantly elevated, and serum catalase (CAT) and malondialdehyde (MDA) content were remarkably restored. The hepatic glutathione (GSH) content was obviously increased and hepatic oxidized glutathione (GSSG) content was reduced dramatically by CF-HT , as compared to the CF treated mice ( p  < 0.05). Moreover, the histopathological damage that hepatocyte hyperplasia and hypertrophy was also significantly ameliorated by treatment with CF-HT . Therefore, the results indicated that CF-HT exerted more potent hypolipidemic activity and definite hepatoprotective effect which may mainly be associated with its antioxidative property in mice. [ABSTRACT FROM AUTHOR]

OBJECTIVE: CD4(+) latency-associated peptide (LAP)(+) regulatory T cells (Tregs) are a newly discovered T cell subset in humans and the role of these cells in patients with acute coronary syndrome (ACS) has not been explored. We designed to investigate whether circulating frequency and function of CD4(+)LAP(+) Tregs are defective in ACS. METHODS: One hundred eleven ACS patients (acute myocardial infarction and unstable angina) and 117 control patients were enrolled in the study. The control patients consisted of chronic stable angina (CSA) and chest pain syndrome (CPS). The frequencies of circulating CD4(+)LAP(+) Tregs and the expression of the transmembrane protein glycoprotein-A repetitions predominant (GARP) on CD4(+) T cells were determined by flow cytometry. The function of CD4(+)LAP(+) Tregs was detected using thymidine uptake. Serum interleukin-10 (IL-10) and transforming growth factor-β protein (TGF-β) levels were detected using ELISA and expression of GARP mRNA in peripheral blood mononuclear cells (PBMCs) was measured by real time-polymerase chain reaction. RESULTS: We found ACS patients had a significantly lower frequency of circulating CD4(+)LAP(+) Tregs, and the function of these cells was reduced compared to controls. The expression of GARP in CD4(+) T cells and the serum levels of TGF-β in ACS patients were lower than those of control patients. The serum levels of IL-10 were similar between the two cohorts. CONCLUSIONS: A novel regulatory T cell subset, defined as CD4(+)LAP(+) T cells is defective in ACS patients.

Broflanilide is a novel insecticide with a unique mode of action on the insect GABA receptor and is registered worldwide for the control of agricultural pests. It shows high efficacy in controlling the fall armyworm (FAW) Spodoptera frugiperda , which is a destructive pest to various crops. FAW was exposed to sublethal concentrations of broflanilide to determine its impact on insect development. Sublethal doses (LD 10 and LD 30) caused failure of ecdysis, reduced body length of larvae, malformation of pupae, and vestigial wing formation in adults. Also, broflanilide at LD 30 significantly reduced the amount of molting hormone (MH). After exposure to LD 10 or LD 30 broflanilide, expression of five Halloween genes, which participate in MH biosynthesis, were found to be altered. Specifically, the transcript levels of SfrCYP307A1 (Spook), SfrCYP314A1 (Shade) and SfrCYP315A1 (Shadow) in 3rd day larvae were significantly decreased as well as SfrCYP302A1 (Disembodied) and SfrCYP306A1 (Phantom) in 5th day pupae. In contrast, the transcript levels of SfrCYP302A1 in 3rd day larvae, SfrCYP307A1 and SfrCYP314A1 in 5th day pupae, and SfrCYP306A1 , SfrCYP307A1 and SfrCYP315A1 in 0.5th day adults were significantly increased. Our results demonstrate that broflanilide caused the failure of ecdysis in FAW possibly by influencing the intake of cholesterol through inhibition of feeding and also via altering expression of genes important for MH biosynthesis. [Display omitted] • Broflanilide prevents ecdysis in larvae, pupae and adults of fall armyworm. • LD 30 broflanilide reduced molting hormone titer in fall armyworm. • Five Halloween genes were identified and cloned in fall armyworm. • Broflanilide inhibits MH level by regulating expression levels of Halloween genes. [ABSTRACT FROM AUTHOR]

Abstract: To make sure the petroleum migrating direction and pool-forming model in the Weixinan sag, 4 wells were chosen to do research on fluid inclusions and petrography. The petroleum inclusions have three types: type I occurs in early cracks of quartz debris grains or the overgrowths inside, type II in the margins or overgrowths of quartz grains, and type III in late cracks of quartz debris grains. According to PVTsim, Ptr and Ttr are modeled and calculated. The results are: type I is 97.9 °C and 19.13 MPa; type II 112.6 °C and 35.05 MPa; type III 157.4 °C and 47.52 MPa. Based on burial history, three fluid-charging events occurred about 33Ma, 26.5Ma and 7Ma ago, respectively. Migration directions and pool forming models are: Fluid type II migrated towards westnorth and northeast respectively to form structural and lithologic reservoirs; Fluid type II migrated to areas surrounding the sag and formed block faulted and buried hill reservoirs; Fluid type III migrated to slopes to form anticlinal reservoirs. Key words: Weixinan Sag, fluid inclusions, PVTsim, trapped pressure, pooling model

Calcium (Ca) is an essential mineral nutrient and plays a crucial signaling role in all living organisms. Increasing Ca content in staple foods such as rice is vital for improving Ca nutrition of humans. Here we map a quantitative trait locus that controls Ca concentration in rice grains and identify the causal gene as GCSC1 (Grain Ca and Sr Concentrations 1), which encodes a chloroplast vesicle localized homo-oligomeric protein. GCSC1 exhibits Ca 2+ transport activity in heterologous assays in yeast and Xenopus laevis oocytes and is involved in the efflux of Ca 2+ from the chloroplast to the cytosol. Knockout of GCSC1 results in increased chloroplast Ca concentration, lower stomatal conductance in leaves and enhanced Ca allocation to grains. Natural variation in grain Ca concentration is attributed to the variable expression of GCSC1 resulting from its promoter sequence variation. Our study identifies a chloroplast localized heavy metal-associated domain containing protein that regulates chloroplast Ca 2+ efflux and provides a way to biofortify Ca in rice to benefit human nutrition., (© 2024. The Author(s).)

Background: Ionotropic γ-aminobutyric acid (GABA) receptor (GABAR) in an insect is the major inhibitory receptor and is one of the most important targets for insecticides. Due to the high spatiotemporal resolution of GABAR, the photopharmacological ligands acting on it in vertebrates but not insect have been developed., Results: In this study, two types of photochromic ligands (PCLs) including DTFIPs (DTFIP1 and DTFIP2) and ABFIPs (p-, m-, and o-ABFIP) were synthesized by incorporating photoswitch azobenzene or dithienylethene into fipronil (FIP), which is the antagonist of insect GABAR. Their photomodulation was measured by mosquito larval behavior, and their potential action mechanism was explored by the two-electrode voltage clamp (TEVC) technique in vitro. DTFIP1 and m-ABFIP exhibited the most significant difference of insecticidal activity by about 90- and 5-fold to mosquito larvae between non-irradiated and irradiated formation, respectively, and allowed for optical control of mosquito swimming activity. TEVC assay results indicated that m-ABFIP and DTFIP1 enable optical control over the homomeric LsRDL-type GABAR, which is achieved by regulating the chloride channel of resistance to dieldrin (RDL)-type GABAR by photoisomerization., Conclusion: Our results suggested that PCLs synthesized from fipronil provide an alternative and precise tool for studying insect ionotropic GABARs and GABA-dependent behavior. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Objective: To establish 10-color fluorescent antibody combination panels for the detection of minimal residual disease (MRD) of acute myeloid leukemia (AML) in our laboratory and discuss the value of clinical application., Methods: According to the antigen expression characteristics of leukemia cells of incipient AML patients, MRD in bone marrow were detected by multiparameter flow cytometry, and the test results were compared with both bone marrow cell morphology and PCR results, then 10-color fluorescent antibody combination panels in our lab for MRD detection was determined., Results: The immunophenotypic characteristics of 392 incipient patients with AML in the First Affiliated Hospital of Zhengzhou University were analyzed, among them 357 (91.07%) cases showed abnormal immunophenotypes, which mainly included cross-lineage expression, cross-stage expression, deficiency of antigen expression or abnormal antigen intensity and other abnormal expression. The 10-color fluorescent antibody combination panels established according to abnormal immunophenotypic characteristics of leukemia cells were applied for detecting MRD in 156 patients with AML, the positive rate (43.6%) was higher than 26.8% of morphology, and the results were highly consistent with PCR detection results (96.49%), moreover, the recurrence rate of MRD positive patients (86.96%) was significantly higher than 5.75% of MRD negative patients. Therefore, this method could truly reflect the load of leukemia cells and prompt change of disease condition., Conclusion: Multiparameter flow cytometry can detect various abnormal immunophenotypes of AML. The 10-color fluorescent antibody combination panels in our lab based on the characteristics of antigens expression in leukemia cells can well detect MRD of leukemia cells, so as to predict relapse and provide basis for clinical treatment.

We examined the effects of channel diversion of Yellow River on the content and stoichiometry of carbon (C), nitrogen (N) and phosphorus (P) in the organs of reeds (stem, leaf, rhizome and fibrous root) and soils in three typical Phragmites australis communities in the Yellow River Delta, including P. australis community in the former Yellow River course abandoned in 1996, P. australis community on the new Yellow River course and the P. australis communities on the intertidal area (far from the abandoned and current channel but affected by the tides). The results showed that foliar C, N and P contents of P. australis were highest in the communities of abandoned Yellow River course. Leaf N, stem C and rhizome P contents were highest in the communities of new Yellow River course. Leaf N and stem C and P contents were highest in the communities of intertidal area. The average leaf C (409.48 g·kg -1 ) and P (1.09 g·kg -1 ) contents in the three habitats were lower than national and global average levels, while leaf N content (21.71 g·kg -1 ) was higher than that of national and global average levels. The mean leaf N:P (20.22) was higher than 16 and the mean soil N:P (0.87) was lower than 14, indicating that the P. australis growth in the three habitats was limited by P. Correlation analysis showed that EC was one of the main factors affecting C:N:P stoichiometry in P. australis . In general, the C and P reserves in P. australis in the study area were low, and N reserve was high. The soil organic carbon content was low, the soil C reserves were large, while the N and P were relatively scarce.

Background: Atherosclerosis is an inflammatory disease involving activation of adaptive and innate immune responses to antigens, including oxidized low-density lipoprotein (oxLDL) and phosphorylcholine (PC). Dendritic cells (DCs), which are antigen-presenting cells that activate T cells, are present in atherosclerotic lesions and are activated in immune organs. However, the mechanism by which PC promotes atherosclerosis is unclear. Methods and Results: To evaluate whether PC promotes atherosclerosis via DCs, 2×10 5 DCs activated by PC-keyhole limpet hemocyanin (DCs+PC-KLH) were injected into ApoE -/- mice and the features of the plaques and the effects of the DCs on cellular and humoral immunity against PC-KLH were determined. Mice injected with DCs+PC-KLH had significantly larger atherosclerotic lesions than controls, with increased inflammation in the lesions and plaque instability. Furthermore, DCs+PC-KLH were characterized using flow cytometry after coculture of bone marrow-derived DCs and naïve T cells. DCs+PC-KLH showed an inflammatory phenotype, with increased CD86, CD40, and major histocompatibility complex Class II molecules (MHC-II), which promoted PC-specific T helper (Th) 1 and Th17 cell differentiation in vivo and in vitro. Moreover, 2 weeks after the administration of DCs+PC-KLH to mice, these mice produced PC- and oxLDL-specific IgG2a, compared with no production in the controls. Conclusions: These findings suggest that DCs presenting PC promote specific immunity to PC, increase lesion inflammation, and accelerate atherosclerosis, which may explain how PC promotes atherosclerosis., Competing Interests: None of the authors have any conflicts of interest to declare., (Copyright © 2021, THE JAPANESE CIRCULATION SOCIETY.)

Objective: To investigate the expression of CD123 in patients with acute myeloid leukemia (AML) and its relationship between clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis., Methods: 365 patients with newly diagnosed AML (except M3) treated in the First Affiliated Hospital of Zhengzhou University were enrolled and retrospective analysis, and multi-parameter flow cytometry was performed to detect the expression of CD123 in myeloid leukemia cell population. CD123≥20% was defined as positive. Clinical features, concomitant fusion gene or gene mutation, efficacy and prognosis of CD123 + and CD123 - patients were compared and analyzed., Results: The positive rate of CD123 in 365 newly diagnosed AML patients was 38.9%. Compared with the CD123 - group, the white blood cell count (WBC), lactate dehydrogenase (LDH) level and bone marrow blast cell ratio were higher in the CD123 + group, and the ratio of NPM1 and DMNT3a gene mutations and the CBFβ-MYH11 fusion gene was significantly increased, while the ratio of CEBPA gene mutation and AML-ETO fusion gene was significantly reduced. The rate of first inducing complete remission and total remission in CD123 + group was significantly lower than that in CD123 - group. There was no significant difference in recurrence rate between the two groups (P>0.05). Survival analysis showed that in 77 AML patients with normal karyotype and intermediate risk, the 2-year overall survival (OS) rate and event-free survival (EFS) rate of the CD123 + group were significantly lower than those of the CD123 - group. Multivariate analysis showed that CD123 was an independent prognostic risk factor for OS and EFS in AML patients with normal karyotype and intermediate risk., Conclusion: CD123 positive indicates that AML patients have higher tumor burden and are more difficult to reach remission. It is an independent risk factor for OS and EFS in patients with normal karyotype and intermediate risk, which is important to evaluate the prognosis of patients with AML without specific prognostic marker.

In various autoimmune diseases, Galecin-9 (Gal-9) has been shown to regulate the T-cell balance by decreasing Th1 and Th17, while increasing the number of regulatory T cells (Tregs). However, the role of Gal-9 in the patients with acute coronary syndrome (ACS) and chronic kidney disease (CKD) remains unclear. This study aims to measure the Gal-9 levels in serum and peripheral blood mononuclear cells (PBMCs) in patients with ACS plus CKD and examine their clinical implication. The serum levels of Gal-9 were determined by enzyme-linked immunosorbent assay (ELISA), the expression levels of Gal-9, Tim-3, and Foxp3 mRNA in PBMCs were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR), and the expression of Gal-9 on the surface of PBMCs and in PBMCs was analyzed by flow cytometry. Furthermore, the correlation of serum Gal-9 levels with anthropometric and biochemical variables in patients with ACS plus CKD was analyzed. The lowest levels of Gal-9 in serum and PBMCs were found in the only ACS group, followed by the ACS+CKD group, and the normal coronary artery (NCA) group, respectively. Serum Gal-9 levels were increased along with the progression of glomerular filtration rate (GFR) categories of G1 to G4. Additionally, serum Gal-9 levels were negatively correlated with high-sensitivity C-reactive protein (hs-CRP), estimated GFR (eGFR), and lipoprotein(a), but positively with creatinine, age, osmotic pressure, and blood urea nitrogen (BUN). Notably, serum Gal-9 was independently associated with hs-CRP, osmotic pressure, and lipoprotein(a). Furthermore, serum Gal-9 levels were elevated in patients with type 2 diabetes (T2DM) and impaired glucose tolerance (IGT) in ACS group. It was suggested that the levels of Gal-9 in serum and PBMCs were decreased in patients with simple ACS and those with ACS plus CKD, and hs-CRP, eGFR, osmotic pressure and T2DM may have an influence on serum Gal-9 levels.

Oxidative stress and subsequent cardiac myocyte apoptosis play central roles in the initiation and progression of myocardial ischemia-reperfusion (I/R) injury. Homeobox transcript antisense intergenic RNA ( Hotair ) was previously implicated in various heart diseases, yet its role in myocardial I/R injury has not been clearly demonstrated. Mice with cardiac-restricted knockdown or overexpression of Hotair were exposed to I/R surgery. H9c2 cells were cultured and subjected to hypoxia/reoxygenation (H/R) stimulation to further verify the role and underlying mechanisms of Hotair in vitro. Histological examination, molecular detection, and functional parameters were determined in vivo and in vitro. In response to I/R or H/R treatment, Hotair expression was increased in a bromodomain-containing protein 4-dependent manner. Cardiac-restricted knockdown of Hotair exacerbated, whereas Hotair overexpression prevented I/R-induced oxidative stress, cardiac myocyte apoptosis, and cardiac dysfunction. Mechanistically, we observed that Hotair exerted its beneficial effects via activating AMP-activated protein kinase alpha (AMPK α ). Further detection revealed that Hotair activated AMPK α through regulating the enhancer of zeste homolog 2/microRNA-451/calcium-binding protein 39 (EZH2/ miR-451 /Cab39) axis. We provide the evidence that endogenous lncRNA Hotair is an essential negative regulator for oxidative stress and cardiac myocyte apoptosis in myocardial I/R injury, which is dependent on AMPK α activation via the EZH2/ miR-451 /Cab39 axis., Competing Interests: The authors declare that there are no conflicts of interests., (Copyright © 2020 Kai Meng et al.)

Background: Fluralaner, a novel pesticide that targets the γ-aminobutyric acid (GABA) receptor (GABAR) subunit of resistant to dieldrin (RDL), exhibits strong potential to be an insecticide to control agricultural insect pests. However, the risk and action of fluralaner to economic insects, e.g., honeybee Apis mellifera Linnaeus, remains unclear., Results: In this study, both oral and contact toxicity of fluralaner to honeybee were found to be 0.13 μg adult -1 . Abamectin, dieldrin, ethiprole, α-endosulfan, fipronil and fluralaner strongly inhibited the GABA-induced current in A. mellifera RDL (AmRDL), expressed in Xenopus laevis oocytes, with median inhibitory concentration (IC 50 ) values of 7.99, 868.1, 27.10, 412.0, 11.21 and 13.59 nM, respectively. The binding free energy and electrophysiological response of AmRDL and insecticides were opposite. The correlation values between toxicity (to A. mellifera) and binding free energy/electrophysiological inhibition (to AmRDL) were at a moderate level., Conclusion: In conclusion, we report for the first time the notable risk of fluralaner to honeybee in vivo and compared the actions of GABAR-targeted insecticides on the AmRDL receptor. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

The ionotropic GABA A receptor (GABA A R) is the main fast inhibitory post-synaptic receptor and is also an important insecticidal target. Effect of insecticides on fish has attracted intensive attention. However, no systematic study on heteromeric zebrafish GABA A R expressed in oocytes has been reported to date. In this study, the α1 subunit, the β2S subunit lacking 47 amino acid residues compared with the β2L subunit, and the γ2 subunit having five transmembrane domains were isolated from zebrafish Danio rerio. The responses of homomeric and heteromeric (α1, β2S and γ2) channels to agonists and GABA A R-targeted compounds were detected with two-electrode voltage clamp. Dose-dependent responses were observed in heteromeric α1β2S, β2Sγ2, and α1β2Sγ2 GABAR channels with EC 50 values at 21.75, 6291, and 33.69 μM for GABA-induced current and 3.28, 155.5, and 3.79 mM for β-alanine-induced current, respectively. However, no response was induced by benzamidine in all GABAR channels. Abamectin, dieldrin, fluralaner and fipronil could strongly inhibited GABA-induced inward current ≥50% at 10 -6  M, while α-endosulfan, flufiprole and ethiprole only inhibited GABA-induced current <50%. This study has clarified the interaction of insecticides with the heteromeric GABA A R channel, which could help us further explore the potential function and toxicological importance of GABA A Rs from D. rerio., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Hydroxytyrosol (HT) is a natural polyphenol antioxidant that exists in olive oil. In the study of multifunctional hypolipidemic of nicotinic derivatives, we found that hydroxytyrosol nicotinate (HT-N) incorporation of niacin with HT displayed ?-glucosidase inhibitory activities in vitro, such as yeast ?-glucosidase (IC 50 ?=?117.72??M) and rat intestinal ?-glucosidases maltase (IC 50 ?=?31.86??M) and sucrase (IC 50 ?=?22.99??M), and had a good control of postprandial blood glucose (PBG). HT-N shown significantly hypoglycemic action by 16.9% and protection of pancreatic tissue in type 2 diabetic mellitus (T2DM) mouse model. HT-N also shown a potent antioxidant activity and property of anti-glycation in vitro, which were benefit for ameliorating diabetic complications. Moreover, HT-N exhibited much significant hypolipidemia, lowering plasma triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 34.6%, 45.8% and 32.1% respectively, in hyperlipidemic mice induced by Triton WR 1339. The results indicated that HT-N has hypolipidemic, hypoglycemic and antioxidant actions. All these properties could be conducive to amelioration of oxidative stress, hyperlipidemia, and diabetes that HT-N may serve as a multifunctional potential therapeutic strategy in diabetic patients with hyperlipidemia., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: To explore the differences of CD146 expression in adult and children's acute B cell lymphoblastic leukemia(B-ALL), and its relation with clinical features, molecular biological and cytogenctic claracteristics., Methods: The expression of CD146 in bone marrow samples from adult and children's B-ALL patients were detected by flow cytometry (FCM) and the relation of CD146 abnormal high expression with the patients' clinical features, molecular biological and cytogenetical characteristics, as well as other antigens were analyzed., Results: The abnormal high expression rates of CD146 in adult and children's B-ALL patients were 29.17% and 9.09% respectively, showing that the expression rate of CD146 in adult patients was higher than that in children's patients(P<0.05). In adult B-ALL, CD146 was positively related with CD64 and CD117, while in children's B-ALL CD146 was positively related with CD71 and CD58 (P<0.05). After 1 course of standardized chemotherapy, the complete remission rates in adult and children's B-ALL patients with abnormal high expression of CD146 both were low as compared with adult and children's B-ALL without abnormal high expression of CD146 (P<0.05)., Conclusion: The expression rate of CD146 in adult B-ALL is higher than that in children's B-ALL. The CD146 positively relates with poor prognostic antigens, the CD146 may be one poor prognosis marker.

Objective: To investigate the expression of N-cadherin in bone marrow leukemic cells derived from acute leukemia patients and its clinical significances., Methods: A total of 113 patients with acute leukemia were enrolled in this study. Flow cytometry was employed to detect the expression of N-Cadherin in bone marrow leukemic cells from acute leukemia patients and the relationships between the N-cadherin expression and the clinical characteristics of patients with acute leukemia were analyzed., Results: The expression of N-Cadherin in bone marrow leukemic cells deriveted from patients with acute leukemia was variable with 0%-99.7%. For adult AML patients, the positive rate of CD34 in N-cadherin + group was significantly higher than that in N-cadherin - group(67.39% vs 33.33%)(P=0.013), while the differences of total CR rate and rate of CR after 1 cycle of induction treatment were not significant between these 2 groups(P>0.05). As to ALL patients, N-cadherin + group had significant lower WBC count (21.31±7.07 vs 51.10±23.69)(P=0.008) and lower percentage of peripheral blood blast (43.22±5.75% vs 66.45±5.65%)(P=0.015). The CR rate after 1 cycle of induction treatment and rate of overall CR were lower and the relapse rate was higher in N-cadherin + ALL group than those in N-cadherin - ALL group, but the differences were not significant (P>0.05). For childhood ALL, the positive rate of CD33 in N-cadherin + group was significantly higher than that in N-cadherin - group(47.62% vs 0%)(P=0.012). The relapse rate was higher in N-cadherin + group than that in N-cadherin - group (30.00% vs 0%)(P=0.115). The median survival time, 3-year overall OS rate and 3-year relapse-free survival rate in N-cadherin - groups of adult AML, non-M3 AML, ALL and chidhood ALL paients were superior to N-cadherin + groups, but the differences were not significant., Conclusion: The expression of N-cadherin in bone marrow leukemic cells relates to some clinical features of patients with acute leukemia and to some extent has inferior effect on survival of patients with acute leukemia.

Objective: To investigate the CD25 expression in patients with acute myeloid leukemia (AML) and its significance., Methods: Clinical data of 168 newly diagnosed AML patients (except APL) were collected. The expression of CD25 in AML patients and its clinical characteristics were retrospectively analyzed., Results: The leukemia cells of 29 out of 168 cases (17.26%) expressed CD25 antigen. Most of CD25 positive AML patients were occurred in patients with unfavourable or normal karyotype, higher WBC and Plt count at diagnosis and higher percentage of blasts in peripheral blood and bone marrow. Compared with CD25(-) AML patients, CD25(+) AML patients had lower CR rate (the CR rate of 1 course of treatment were 49.02% and 16.00%, respectively, P < 0.05, the CR rate of 2 courses of treatment were 74.60% and 46.67%, respectively, P < 0.05), and the OS time of CD25(+) AML patients were obviously shorter (P < 0.05). The OS in CD25(+) AML patients with unfavorable karyotype were not significantly different from that in patients with intermediate karyotype (P < 0.05)., Conclusion: The CD25(+) AML patients have some typical clinical features, and the expression of CD25 in AML is an risk factor independent of the chromosome karyotype in terms of low complete remission rate and short survival time.

Objective: To investigate the expression of N-Cadherin in the patients with multiple myeloma (MM) and to explore its clinical significance., Methods: A total of 64 patients with multiple myeloma were enrolled in this study. The expression of N-Cadherin in bone marrow CD38⁺/CD138⁺ cells from multiple myeloma patients was detected by flow cytometry. The relationship between N-Cadherin expression and clinical prognostic factors was analyzed., Results: Among 64 cases of MM, the expression of N-Cadherin in 17 patients (26.56%) was high (> 20%), while that in 47 cases (73.44%) was low (< 20%); The differences of N-Cadherin expression in disease staging and classification, known prognostic factors, myeloma cell antigen expression and bone damage between patients with high and low N-Cadherin expression were not statistically different; the difference N-Cadherin expression in genetic abnormalities such as D13S319 deletion, RB1 deletion and IGH gene rearrangement between above-methioned two groups was not significant. The 1q21 amplification rate in the group with high expression of N-Cadherin was enhanced significently; the overall survival (OS) times of patients with abnormally high and low expression levels of N-Cadherin were 26.7 months and 55.5 months respectively, and the difference was statistically significant (P < 0.05)., Conclusion: The high expression of N-Cadherin in multiple myeloma may be one of the indicator for poor prognosis of MM, which may be related with 1q21 amplification.

Objective: To explore the expression of PD-L1 in acute leukemia patients, and to analyze the relationship of PD-L1 expression with the patients' clinical characteristics and prognosis., Methods: The expression of PD-L1 in leukemia cells of 75 patients including 59 de novo patients and 16 relapse/refractory patients with acute leukemia was detected by the flow cytometry, the clinical information was collected, and the therapeutic efficacy of de novo patients was analyzed., Results: The PD-L1 was expressed in human acute leukemia cells with total expression rate 32% (24/75), and its expression level in AML-M5 was higher than that in other leukemias [56.3% (9/16) vs 25.4% (15/59)], there was statistical significance (P = 0.019). The PD-L1 possitive rate in relapse/refractory group was higher than that in de novo patient group [(56.3% (9/16) vs 25.4% (15/59)], and there was statistical significance (P = 0.019). In 59 de novo patients, the CR rate of PD-L1 positive group after 1 course of chemotherapy was lower than that in PD-L1 negative group (66.7% vs 71.4%), the CR rate of PD-L1 positive group after 2 courses of chemotherapy was also lower than that in PD-L1 negative group (70% vs 88.6%). The relapse rate and the proportion of refractory patients in PD-L1 possitive group were higher than those in PD-L1 negative group. The expression of PD-L1 did not correlated with the clinical parameters, such as sex, age, extramedullary infiltration, percentage of blast cells in bone marrow, counts of WBC, RBC and platelet, as well as molecular biological features and cytogenetical characteristics., Conclusion: PD-L1 is expressed in human acute leukemia cells, and may be involved in the immune escape and primary resistant mechanisms, PD-L1 may be used as an indicator for evaluation of the the patients' prognosis and reocurrence.

Objective: CD4(+) latency-associated peptide (LAP)(+) regulatory T cells (Tregs) are a newly discovered T cell subset in humans and the role of these cells in patients with acute coronary syndrome (ACS) has not been explored. We designed to investigate whether circulating frequency and function of CD4(+)LAP(+) Tregs are defective in ACS., Methods: One hundred eleven ACS patients (acute myocardial infarction and unstable angina) and 117 control patients were enrolled in the study. The control patients consisted of chronic stable angina (CSA) and chest pain syndrome (CPS). The frequencies of circulating CD4(+)LAP(+) Tregs and the expression of the transmembrane protein glycoprotein-A repetitions predominant (GARP) on CD4(+) T cells were determined by flow cytometry. The function of CD4(+)LAP(+) Tregs was detected using thymidine uptake. Serum interleukin-10 (IL-10) and transforming growth factor-β protein (TGF-β) levels were detected using ELISA and expression of GARP mRNA in peripheral blood mononuclear cells (PBMCs) was measured by real time-polymerase chain reaction., Results: We found ACS patients had a significantly lower frequency of circulating CD4(+)LAP(+) Tregs, and the function of these cells was reduced compared to controls. The expression of GARP in CD4(+) T cells and the serum levels of TGF-β in ACS patients were lower than those of control patients. The serum levels of IL-10 were similar between the two cohorts., Conclusions: A novel regulatory T cell subset, defined as CD4(+)LAP(+) T cells is defective in ACS patients.

Colorectal cancer is one of the most commonly diagnosed cancers and is a leading cause of cancerrelated death worldwide. In this study, we aimed to examine the expression of PTEN in human colorectal cancer cell lines HCT-8 and to further investigate the functions of PTEN in colorectal cancer cells. Therefore, we established stably transfected HCT-8 cell lines expressing siRNA targeting the PTEN gene. Cell proliferation and cell migration of the siPTEN cells were characterized by the CCK-8 assay and the Transwell assay, respectively. Our results show that constitutive knockdown of the PTEN gene in siPTEN cells significantly promoted cell proliferation and migration. These results suggest that PTEN may play important roles in colorectal cancer cell proliferation and migration.

Atherosclerosis is an inflammatory disease characterized by extensive lipid deposition and atherosclerotic plaque formation in the intima. Interleukin (IL)-37 is anti-inflammatory cytokine in the IL-1 ligand family. Given that IL-37 plays an important function in the development and progression of inflammatory and autoimmune diseases, it may be associated with the development of atherosclerosis. IL-37, which is normally expressed at low levels in peripheral blood mononuclear cells (PBMC), mainly monocytes, and dendritic cells (DC), is rapidly up-regulated in the inflammatory context, and therefore IL-37 conversely inhibits the production of inflammatory cytokines in PBMC and DC. In addition, IL-37 effectively suppresses the activation of macrophage and DC. It is not controversial that the activation of macrophage and DC and the over-expression of inflammatory cytokines are critical component elements in inflammatory process of atherosclerosis. Therefore, IL-37 may play a protective role in atherosclerosis through inhibition of inflammatory cytokines production and suppression of macrophage and DC activation.

This study was aimed to investigate the clinical features of CD56(+) patients with acute monocytic leukemia (AML-M5) and their prognostic significance. The data of 76 newly-diagnosed patients from our hospital were analyzed retrospectively. Patients were divided into two groups: CD56(+) group (21 patients) and CD56(-) group (55 patients). The clinical features, CR rate, relapse rate, the duration of CR, and survival time of patients between the two groups were compared. The results indicated that the CD56(+) antigen was observed in 21 patients (27.6%), their median age was 51.5 years and with a range 16 - 70 years. Of the 21 CD56(+) patients, the high WBC count was found in 57.1% CD56(+) patients (12/21), but it only in 15% CD56(-) patients (P < 0.05). The extramedullary infiltration was seen in 13 CD56(+) patients, and accounted for 62% (13/21), meanwhile this infiltration was found in 18 CD56(-) patients (18/55) and accounted for 33% (P < 0.05). All cases immunophenotypically highly expressed CD13, CD33, CD64, CD11b, cMPO, CD38, in which only the expression frequency of CD11b was positively related with CD56 (r = 0.59, P < 0.05). The CR rate in CD56(+) group accounted for 60.0%, and had no significant difference in comparison with that in CD56(-) group. In CD56(+) group the relapse rate was 75% (P = 0.042), the mean duration of CR was 5.5 months (95%CI, 3.1 - 8.6, P = 0.002), the median overall survival time was 10.1 months (95%CI, 2.3 - 16.3, P = 0.001). and all these had statistical significance as compared with that in CD56(-) group. It is concluded that CD56(+) AML-M5 patients always complicate with high WBC count and extramedullary infiltration, their CR rate and duration of CR are lower and shorter respectively, their relapse rate and prognosis are high and poor respectively.

This study was purposed to investigate the dynamically monitoring minimal residual disease (MRD) by flow cytometry (FCM) in patients with acute leukemia (AL) after complete remission and its relation with prognosis. From October 2010 to May 2012, 58 cases of AL (including 45 cases of AML and 13 cases of ALL) were regularly monitored for MRD in bone marrow by FCM and their bone marrow morphology was observed by light microscopy at the same time which continued to relapse or to follow-up deadline in the Department of Hematology, the First Affiliated Hospital of Zhengzhou University. Through average follow-up for 9 months (3 - 21 months), the average MRD level of patients with CR was got. And the prognostic value of MRD level at different time points in AL patients after CR was analysed and summarized. MRD ≥ 1% was defined as positive, otherwise, as negative. The results showed that the maximum and minimum MRD levels of 45 AML patients were 9.57% and 0.01% respectively, the average was 0.67%; the maximum and minimum MRD levels of 13 cases of ALL patients were 7.9% and 0.0016% respectively, the average was 0.99%. Among 44 cases after induction therapy, the relapse rate of MRD(+) group was 53.3% (8/15), the relapse rate of MRD(-) group was 10.3% (3/29), and the relapse rate of MRD(+) group was higher than that of MRD(-) group (χ(2) = 7.58, P = 0.006). Among 58 cases after the first consolidatory therapy, the relapse rate of MRD(+) group was 62.5% (5/8), the relapse rate of MRD(-) group was 16.0% (8/50), and the relapse rate of MRD(+) group was higher than that of MRD(-) group (χ(2) = 6.11, P = 0.013). It is concluded that MRD detected by FCM has a large range (10(-6) - 10(-2)), which can not be used as a single indicator of complete remission. When MRD ≥ 1% after induction therapy and the first consolidatory therapy, the relapse rate significantly increases, MRD can be used as a sensitive indicator for prognosis.

This study was purposed to explore the correlation of chromosome karyotype with dyshaematopoiesis and reticulin in myelodysplastic syndrome (MDS). The data of 202 MDS patients diagnosed and treated in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed in term of chromosome karyotype, dyshaematopoiesis and reticulin detection results. The chromosome karyotypes were categorized according to the International Prognostic Scoring System (IPSS). The results showed that there was a positive correlation between chromosome karyotype grading and number of lineages with dyshaematopoiesis (r = 0.443, P < 0.05). The detected rates of multilineage dyshaematopoiesis in patients with good, intermediate and poor chromosome karyotypes were 44.4%, 71.4% and 96.3% respectively. There was a positive correlation between chromosome karyotype grading and reticulin grading (r = 0.451, P < 0.05). The positive rates of reticulin in patients with good grading, intermediate and poor chromosome karyotypes were 36.8%, 64.3% and 92.6% respectively. The detected rate of multilineage dyshaematopoiesis, number of lineages with dyshaematopoiesis, the positive rate of reticulin and reticulin grade in patients with poor karyotypes were higher than those in patients with intermediate or good chromosome karyotypes (separately P < 0.01). The above data in patients with intermediate chromosome karyotypes were higher than those in patients with good chromosome karyotypes (separately P < 0.01). It is concluded that the chromosome karyotype grading positively correlates with the number of lineages with dyshaematopoiesis and reticulin grading. When the chromosome karyotype changed from good to poor, the detected rate of multilineage dyshaematopoiesis, number of lineages with dyshaematopoiesis, positive rate of reticulin and reticulin grading became higher and higher.