Effects of vitamin D and/or calcium intervention on sleep quality in individuals with prediabetes: a post hoc analysis of a randomized controlled trial.

PURPOSE: The aim of this study was to evaluate the effects of vitamin D and/or calcium supplementation on sleep quality in individuals with prediabetes. METHODS: A 24-week randomized controlled trial (RCT) was conducted in a 212 Chinese population with prediabetes. Participants were randomly assigned to four groups: vitamin D + calcium group (1600 IU/day + 500 mg/day, n = 53), vitamin D group (1600 IU/day, n = 54), calcium group (500 mg/day, n = 51), and control group (placebo, n = 54). The Pittsburgh Sleep Quality Index (PSQI) was used as the primary outcome to assess sleep quality. Questionnaires and fasting blood samples were collected at baseline and post-intervention for demographic assessment and correlation index analysis. RESULTS: After a 24-week intervention, a significant difference was observed in serum 25(OH)D concentration among the four groups (P < 0.05), and the total PSQI score in vitamin D + calcium group was lower compared to the preintervention levels. Subgroup analyses revealed improved sleep quality with calcium supplementation (P < 0.05) for specific groups, including women, individuals with a low baseline 25(OH)D level (< 30 ng/mL), and individuals in menopause. Moreover, correlation analysis revealed a negative correlation between the extent of change in sleep efficiency scores before and after the calcium intervention and the degree of change in insulin efficiency scores (r = - 0.264, P = 0.007), as well as the magnitude of change in islet beta cell function (r = - 0.304, P = 0.002). CONCLUSIONS: The combined intervention of vitamin D and calcium, as well as calcium interventions alone, exhibits substantial potential for improving sleep quality in individuals with prediabetes. CLINICAL TRIAL REGISTRATION: The trial was registered in August 2019 as ChiCTR190002487.

[Inhibitory Effect of Metformin and Arsenic Trioxide on KG1a Cell Proliferation].

OBJECTIVE: To investigate the effect of metformin and arsenic trioxide on KG1a cells proliferation of acute myeloid leukemia and its possible mechanism. METHODS: CCK-8 method was used to detect the killing effect of metformin, arsenic trioxide and combined application on KG1a cells. Annexin V-FITC/PI Dual Stain Flow Cytometry was used to detect the effect of combined application on apoptosis of KG1a cells. Western blot was used to detect the expression of intracellular apoptosis-,autophagy-related protein. RESULTS: Metformin and arsenic trioxide alone or in combination could inhibit the proliferation of KG1a cells and induce apoptosis of KG1a cells, and the proliferation inhibition rate and apoptosis rate in the combined drug group were higher than those in the drug group alone(P <0.05). The combination of drugs induced upregulation of Caspase 8 protein and P62 protein expression and was higher than that in the drug group alone(P <0.05). CONCLUSION: Metformin can synergize with arsenic trioxide to kill KG1a cells, and its mechanism of action may be related to inducing apoptosis and enhancing autophagy.

Association of parathyroid hormone with risk of hypertension and type 2 diabetes: a dose-response meta-analysis.

BACKGROUND: Despite an increase in parathyroid hormone (PTH) has been reported to be associated with a higher risk of hypertension and type 2 diabetes (T2D), the comprehensive evaluation of the dose-response relationship between PTH and hypertension and T2D remains ambiguous. Therefore, a dose-response meta-analysis was performed to quantitatively investigate this association. METHODS: PubMed, Web of Science, and Embase were systematically searched up to May 2023. Random-effect models were used to estimate the summary odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were used to model the dose-response association. RESULTS: Ten articles (including 13 studies) were identified, with a total of 11,878 cases and 51,234 participants in the meta-analysis. Of these studies, eight (five cohort and three cross-sectional) studies investigated the association of PTH with hypertension; five (two cohort and three cross-sectional) studies assessed the association of PTH with T2D. The results showed a positive relationship between PTH and the risk of hypertension (OR,1.24, 95% CI: 1.16-1.33). We found a linear association between PTH and hypertension (Pnon-linearity= 0.222). In the dose-response analysis, the risk of hypertension increased 5% for every 10 pg/ml increase in PTH (OR,1.05, 95% CI: 1.02-1.08). The pooled OR of T2D risk for a 10 pg/ml increase in PTH was 1.00 (95% CI: 0.98-1.02). CONCLUSIONS: Elevated PTH is associated with an increased risk of hypertension. However, the evidence of the association between PTH and T2D is limited, and more well-designed studies need to be explored.

A fresh pH-responsive imipenem-loaded nanocarrier against Acinetobacter baumannii with a synergetic effect.

In recent years, the treatment of Acinetobacter baumannii infections has become a pressing clinical challenge due to its increasing incidence and its serious pathogenic risk. The research and development of new antibacterial agents for A. baumannii have attracted the attention of the scientific community. Therefore, we have constructed a new pH-responsive antibacterial nano-delivery system (Imi@ZIF-8) for the antibacterial treatment of A. baumannii. Due to its pH-sensitive characteristics, the nano-delivery system offers an improved release of the loaded imipenem antibiotic at the acidic infection site. Based on the high loading capacity and positive charge of the modified ZIF-8 nanoparticles, they are excellent carriers and are suitable for imipenem loading. The Imi@ZIF-8 nanosystem features synergistic antibacterial effects, combining ZIF-8 and imipenem to eliminate A. baumannii through different antibacterial mechanisms. When the loaded imipenem concentration reaches 20 µg/mL, Imi@ZIF-8 is highly effective against A. baumannii in vitro. Imi@ZIF-8 not only inhibits the biofilm formation of A. baumannii but also has a potent killing effect. Furthermore, in mice with celiac disease, the Imi@ZIF-8 nanosystem demonstrates excellent therapeutic efficacy against A. baumannii at imipenem concentrations of 10 mg/kg, and it can inhibit inflammatory reaction and local leukocyte infiltration. Due to its biocompatibility and biosafety, this nano-delivery system is a promising therapeutic strategy in the clinical treatment of A. baumannii infections, providing a new direction for the treatment of antibacterial infections.

Effect of Vitamin D and/or Calcium Supplementation on Pancreatic ß-Cell Function in Subjects with Prediabetes: A Randomized, Controlled Trial.

So far, the potential role of vitamin D in ß-cell function remains a matter of debate. Therefore, a randomized, placebo-controlled trial (RCT) was conducted to evaluate the effect of a vitamin D supplement with or without calcium on ß-cell function in a Chinese population with prediabetes. Two hundred and forty-three subjects were randomly assigned in a 2-by-2 factorial-design RCT to receive either 1600 IU/day vitamin D3 with/or 500 mg/day calcium for 24 weeks. The results showed that oral administration of vitamin D and calcium could increase the secretion of insulin. Vitamin D-insufficient individuals displayed an increment in the disposition index (adjusted change = 0.31, 95%CI: 0.07, 0.56) after treatment by vitamin D + calcium. It illustrated that supplementation with vitamin D and calcium might improve the function of pancreatic ß-cell in prediabetes with low serum 25(OH)D levels. However, further studies are needed to confirm the findings. Given the low vitamin D content in natural foods, it is necessary to fortify processed foods with vitamin D.

A healthier water use strategy in primitive forests contributes to stronger water conservation capabilities compared with secondary forests.

Water conservation is an important ecological function of forest ecosystems, plant water use strategy is a key factor in regulating forest ecosystem water balance. However, there are still insufficient studies on the water conservation capacity and water use strategies of different forest types, especially in climate-sensitive areas. In this study, we determined the stable isotope values (δD, δ18O and d-excess) of plant water, soil water and precipitation from two typical stand types (primary forest and secondary forest) on Changbai Mountain to reveal plant water use and evaluated the water conservation capacity. The results indicated that rainwater infiltrated into the soil combined with piston flow and preferential flow in the primary forest, and preferential flow was the only form of flow in the secondary forest. The main tree species in the primary forest formed a relatively stable water use niche. Among them, the water use pattern of Quercus mongolica Fisch. ex Ledeb (Qm.) was transformed between shallow and deep soil layers with strong ecological plasticity. The dominant species in secondary forest derived water from similar soil layers with intense interspecific competition. By comparing the water use patterns, the secondary forest conformed to the hypothesis of "two water worlds", while the primary forest conformed to the hypothesis of one reservoir. The primary forest ecosystem had stronger water conservation capacity than secondary forest ecosystem due to the regulable water use strategies of plants and the stable water conservation capacity of the soil. These results will provide theoretical support and a reference for plan future forest management strategies in the climate-sensitive areas.

GC gene polymorphisms found with type 2 diabetes and low vitamin D status among rural Chinese in Henan province.

BACKGROUND AND OBJECTIVES: Accumulating evidence suggests that vitamin D may be involved in the pathogenesis of type 2 diabetes (T2D). Group-specific component (GC) gene is the most important transporter of vitamin D and plays a regulatory role in vitamin D metabolism. We aimed to evaluate the association of GC gene polymorphisms with T2D susceptibility and vitamin D status in the Chinese rural population. METHODS AND STUDY DESIGN: A total of 1372 subjects were eligible in this cross-sectional study. Three SNPs of the GC gene (rs7041, rs4588, and rs2282679) were genotyped by TaqMan probe assays. Logistic regression and Kruskal-Wallis one-way analysis were performed to determine the possible risk genotype for T2D and vitamin D metabolite concentrations, respectively. RESULTS: The serum 25-hydroxyvitamin D3 [25(OH)D3] and vitamin D binding protein (DBP) concentrations were significantly lower in the T2D group than the non-T2D group. GG genotype carriers of rs7041 (T>G) were more likely to have T2D compared with AA carriers (OR=2.00, 95% CI: 1.19-3.37). Variants of rs4588 (C>A) and rs2282679 (A>C) were associated with a lower risk of T2D under the dominant inheritance model (OR=0.65, 95% CI: 0.48-0.88; OR=0.66, 95% CI: 0.49-0.90, respectively). We further found that non-T2D subjects with the AA genotype of rs4588 had significantly higher 25(OH)D3 concentrations than the CC genotype (p=0.022). In contrast, the T2D cases with the CC genotype of rs2282679 had lower DBP concentrations compared to the AA genotype (p=0.020). CONCLUSIONS: Our study indicates a potential role for GC gene polymorphisms in T2D susceptibility and vitamin D metabolite concentrations in the Chinese rural population.

The Association Between GC Gene Polymorphisms and Metabolic Syndrome in Chinese Rural Population: A Case-Control Study.

BACKGROUND: GC (group-specific component globulin) encoding VDBP (Vitamin D binding protein) polymorphisms have been associated with susceptibility to some diseases such as diabetes, obesity, osteoporosis, and polycystic ovary syndrome, but the evidence for metabolic syndrome (MetS) in the Chinese rural population is inconclusive. Therefore, we investigated the relationship between GC variants (rs7041, rs4588, rs2282679, and rs705117) and MetS risk as well as VDBP levels in the Chinese rural population. PATIENTS AND METHODS: The participants (range of age: 20-90 years) of this case-control study were recruited from the northern Chinese Han rural population. We matched 445 MetS cases with non-MetS controls in a 1:1 ratio by sex, age (within 5 years). Real-time PCR technology was carried out by TaqMan assays to examine the four variants of rs7041, rs4588, rs2282679, and rs705117 within the GC gene. To identify the association of GC gene polymorphisms with MetS, we calculated ORs using a conditional logistic regression model adjusted for potential confounding factors. RESULTS: We observed inverse associations of CA and AA genotypes of rs4588 with risk of MetS (OR = 0.678, 95% CI 0.505-0.910, P = 0.010; 0.603, 95% CI 0.373-0.973, P = 0.039, respectively) compared with carriers of CC genotype. A similar relationship was also found between rs2282679 and MetS, showing that carrying AC genotype of rs2282679 can decrease the risk of MetS (OR = 0.683, 95% CI 0.509-0.917, P = 0.011) compared with carriers of AA genotype. The results of correlation analysis between MetS components and GC polymorphisms showed that the ORs of AA genotype of rs4588 with high level of TG (triglycerides) and low level of HDL-C (high-density lipoprotein cholesterol) were 0.473 (95% CI 0.245-0.911, P = 0.025) and 0.268 (95% CI 0.117-0.615, P = 0.002), respectively; the ORs of CC genotype of rs2282679 with high level of TG and low level of HDL-C were 0.428 (95% CI 0.217-0.842, P = 0.014) and 0.263 (95% CI 0.110-0.628, P = 0.003), respectively. However, there was no significant association between the concentration of VDBP and MetS risk. CONCLUSION: Among the Chinese rural population, GC polymorphism was associated with lower metabolic syndrome susceptibility, which might be through affecting blood lipid levels (TG and HDL-C).

Effects of a new fermented soya bean meal on growth performance, serum biochemistry profile, intestinal immune status and digestive enzyme activities in piglets.

BACKGROUND: Fermented soya bean meal (FSBM) is believed to have improved nutritional qualities compared with soya bean meal (SBM) and is also cheaper than soya protein concentration (SPC) and fish meal (FM). Therefore, the present study was conducted to compare the effects of FSBM replacing SBM, SPC and FM in diets on growth performance, serum biochemistry profile, short-chain fatty acid concentrations in digesta, intestinal mucosal enzyme activities, intestinal proinflammatory cytokine concentrations and morphology in weaned piglets. One hundred and twenty 28-day-old piglets (Duroc × Landrace × Yorkshire, body weight: 6.73 ± 1.14 kg) were randomly allocated to four treatment diets (six replicate pens with five piglets per pen) containing SBM, SPC, FM or FSBM as the protein source, respectively. RESULTS: Dietary FSBM supplementation improved average daily gain (p < 0.05), gain to feed ratio (p < 0.05), and digestibility of dry matter, gross energy, crude protein and organic matter (p < 0.05) in pigs compared with those fed SBM during 0-14 days and reduced diarrhoea rate (p < 0.05) compared with those fed SBM and FM during 0-14 days. Moreover, pigs fed FBSM had greater IgA and IgM contents and antioxidase activities than those provided SBM and SPC on day 14. In addition, the butyrate concentration in the cecum of pigs fed FSBM was greater than those fed the other diets (p < 0.05), and the trypsin activity in duodenum and jejunum of pigs provided FSBM was greater than those fed SBM (p < 0.05). Moreover, higher villus height (p < 0.05) and villus height to crypt depth ratio (p < 0.05) and lower crypt depth (p < 0.05) in the duodenum of pigs fed FSBM were observed, and pigs fed FSBM had a lower (p < 0.05) TNF-α concentration in jejunum compared with those fed SBM. CONCLUSIONS: In conclusion, dietary FSBM supplementation to replace SBM, SPC and FM could improve piglets' growth performance, intestinal health and immune function.

Numerical simulation flow dynamics of an intracranial aneurysm.

BACKGROUND: Computational fluid dynamics provides a new method for the study of the blood flow characteristics of the formation and development of intracranial aneurysms. OBJECTIVE: To compare blood flow characteristics between the healthy internal carotid artery and normal intracranial aneurysms. METHODS: The internal carotid arteries were simulated to obtain hemodynamic parameters in one patient. RESULTS: The internal carotid artery associated with aneurysm presents low wall shear stress, high oscillatory shear index, and high particle retention time compared with the normal internal carotid artery. CONCLUSIONS: There are differences in blood flow between the normal internal carotid artery and intracranial aneurysm. The vortex of the aneurysm will produce turbulence, indicating that it is unstable, which results in the growth and rupture of the aneurysm.

Circular RNA circ_0023404 serves as a miR-636 sponge to promote malignant behaviors in cervical cancer cells through upregulation of CYP2S1.

Cervical cancer is the most common malignant gynecological tumor. Circular RNA (circRNA) circ_0023404 is reported to be upregulated in cervical cancer cells. This aim is to explore the role and mechanism of circ_0023404 in cervical cancer. circ_0023404, microRNA-636 (miR-636), and cytochrome P450 2S1 (CYP2S1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, migration, invasion, and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, 5-ethynyl-2'-deoxyuridine (EDU) assay, colony formation assay, transwell assay, and cytometry assay. Protein levels of cyclin D1, matrix metallopeptidase 9 (MMP9), Bcl-2-associated X protein (Bax), and CYP2S1 were examined by western blot assay. The binding relationship between miR-636 and circ_0023404 or CYP2S1 was predicted by Circinteractome or targetscan, and then verified by a dual-luciferase reporter assay and RNA pull-down assay. circ_0023404 and CYP2S1 expression were increased, and miR-636 was decreased in cervical cancer tissues and cells. Moreover, circ_0023404 knockdown could repress proliferation, migration, invasion, and promote apoptosis of cervical cancer cells in vitro. Mechanically, circ_0023404 could regulate CYP2S1 expression by sponging miR-636. circ_0023404 silencing could attenuate the progression of cervical cancer cells partly by targeting the miR-636/CYP2S1 axis, hinting at a promising therapeutic target for cervical cancer.

Multi frequency multi bit amplitude modulation of spoof surface plasmon polaritons by schottky diode bridged interdigital SRRs.

Multi-frequency multi-bit programmable amplitude modulation (AM) of spoof surface plasmon polaritons (SPPs) is realized at millimeter wave frequencies with interdigital split-ring resonators (SRRs) and In-Ga-Zn-O (IGZO) Schottky diodes. Periodic SRRs on a metal line guide both SRR mode and spoof SPP mode, the former of which rejects the spoof SPP propagation at the SRR resonant frequencies. To actively modulate the amplitude of spoof SPPs, IGZO Schottky diodes are fabricated in the SRR gaps, which continuously re-configure SRRs to metallic loops by applying bias. Interdigital gaps are designed in SRRs to increase the capacitance, thus red shifting the resonant frequencies, which significantly broadens the operation bandwidth of multi-frequency AM. Thus, cascading different kinds of interdigital SRRs with Schottky diodes enables multi-frequency multi-bit AM programmable. As a demonstration, a dual-frequency device was fabricated and characterized, which achieved significant multi-bit AM from -12.5 to -6.2 dB at 34.7 GHz and from -26 to -8.5 dB at 50 GHz independently and showed programmable capability.

Serum macrophage migration inhibitory factor as a potential biomarker to evaluate therapeutic response in patients with allergic asthma: an exploratory study.

BACKGROUND: Previous studies have shown that macrophage migration inhibitory factor (MIF) is involved in the pathogenesis of asthma. This study aimed to investigate whether serum MIF reflects a therapeutic response in allergic asthma. METHODS: We enrolled 30 asthmatic patients with mild-to-moderate exacerbations and 20 healthy controls, analyzing the parameter levels of serum MIF, serum total immunoglobulin E (tIgE), peripheral blood eosinophil percentage (EOS%), and fractional exhaled nitric oxide (FeNO). Lung function indices were used to identify disease severity and therapeutic response. RESULTS: Our study showed that all measured parameters in patients were at higher levels than those of controls. After one week of treatment, most parameter levels decreased significantly except for serum tIgE. Furthermore, we found that serum MIF positively correlated with EOS% as well as FeNO, but negatively correlated with lung function indices. Receiver operator characteristic (ROC) curve analysis indicated that among the parameters, serum MIF exhibited a higher capacity to evaluate therapeutic response. The area under the curve (AUC) of MIF was 0.931, with a sensitivity of 0.967 and a specificity of 0.800. CONCLUSIONS: Our results suggested that serum MIF may serve as a potential biomarker for evaluating therapeutic response in allergic asthma with mild-to-moderate exacerbations.

The influence of VDR polymorphisms on the type 2 diabetes susceptibility in Chinese: an interaction with hypertriglyceridemia.

Evidence shows that mutations in vitamin D receptor (VDR) have been linked with an increased risk of type 2 diabetes (T2D). However, the interaction effect between VDR variants and environmental factors on the T2D susceptibility remained unclear. Therefore, the current study was conducted to explore the joint effect of VDR polymorphisms and serum triglyceride level on T2D. A total of 2017 participants were included in the cross-sectional study. Taqman probe assays were applied to rs3847987 and rs739837 genotyping. Multiple logistic regression and general linear model were used to examine the effect of interaction between VDR variants and TG on T2D susceptibility and fasting serum glucose, respectively. The results showed that rs739837 polymorphism was significantly associated with an increased risk of T2D under the dominant model (OR = 1.30, 95% CI 1.02-1.66), after adjusting for potential risk factors. Meanwhile, there was a significant additive interaction between rs3847987 and hypertriglyceridemia (synergy index [SI]: 2.98, 95% CI: 1.23-7.23) and between rs739837 and hypertriglyceridemia (SI: 2.36, 95% CI: 1.05-5.31) on T2D susceptibility. Additionally, a significant linear association between fasting glucose and rs3847987 had been found at high triglyceride level (> 1.90 mmol/L) with an inversely concentration-dependent manner. The study provided further evidence that rs739837 and high level of triglyceride were both associated with higher T2D susceptibility in Chinese population. Additionally, the detrimental effect of VDR variants on T2D could be modified by hypertriglyceridemia status.

Assessment of whether the rabbit subscapularis tendon model is suitable for studying the human chronic rotator cuff pathology: Discovery of a new ligament connecting the glenoid and subscapularis tendon.

OBJECTIVE: This study aimed to investigate the anatomical relationship between the subscapularis tendon and glenosubscapularal ligament (GSL) that we accidentally identified from our previous study on a rabbit shoulder model and to determine whether this anatomical relationship has an impact on the rabbit shoulder model for studying the human chronic rotator cuff pathology. METHODS: In this study, 15 male New Zealand rabbits aged 12 weeks and weighing 2.5 kg were used. Moreover, 3 rabbits were sacrificed for the anatomical and histological investigation of the relationship between the subscapularis tendon and GSL at baseline. The remaining 12 rabbits underwent the subscapularis tendon tenotomy from the lesser tuberosity using a standardized procedure. The GSL was cut on the left side and preserved on the right side. For histomorphometric analysis, 6 rabbits were first sacrificed at 6 weeks and then the remaining 6 rabbits at 12 weeks. RESULTS: In all the rabbits, GSL was identified, connecting the upper portion of glenoid and subscapularis muscle-tendon junction. The mean thickness of the middle portion of GSL was 1.1±0.2 mm; the mean length of GSL was 8.4±2.3 mm. The mean widths of the proximal and distal attachments were 2.4±0.3 and 4.2±0.5 mm, respectively. The mean size of the native subscapularis muscle fibers was 122.6±4.3 µm2. The mean size of the muscle fibers in shoulders with tenotomy alone was 112.6±6.2 and 102.6±4.8 µm2 at 6 and 12 weeks, respectively. The mean size of the muscle fibers in shoulders with tenotomy plus GSL cut severing was 88.3±9.7 and 56.4±5.2 µm2 at 6 and 12 weeks, respectively. The significant muscle atrophy was observed both at 6 and 12 weeks in the shoulders with tenotomy plus GSL cut compared with those with tenotomy alone as well as those with the native subscapularis. However, the muscle atrophy was not significantly different in the shoulders with tenotomy alone at different time points. CONCLUSION: Because GSL may prevent the subscapularis retraction, the rabbit subscapularis tendon model may not be suitable for studying the human chronic rotator cuff pathology if GSL is neglected or preserved.

Driving Factors and Future Prediction of Land Use and Cover Change Based on Satellite Remote Sensing Data by the LCM Model: A Case Study from Gansu Province, China.

Land use and cover change (LUCC) is an important issue affecting the global environment, climate change, and sustainable development. Detecting and predicting LUCC, a dynamic process, and its driving factors will help in formulating effective land use and planning policy suitable for local conditions, thus supporting local socioeconomic development and global environmental protection. In this study, taking Gansu Province as a case study example, we explored the LUCC pattern and its driving mechanism from 1980 to 2018, and predicted land use and cover in 2030 using the integrated LCM (Logistic-Cellular Automata-Markov chain) model and data from satellite remote sensing. The results suggest that the LUCC pattern was more reasonable in the second stage (2005 to 2018) compared with that in the first stage (1980 to 2005). This was because a large area of green lands was protected by ecological engineering in the second stage. From 1980 to 2018, in general, natural factors were the main force influencing changes in land use and cover in Gansu, while the effects of socioeconomic factors were not significant because of the slow development of economy. Landscape indices analysis indicated that predicted land use and cover in 2030 under the ecological protection scenario would be more favorable than under the historical trend scenario. Besides, results from the present study suggested that LUCC in arid and semiarid area could be well detected by the LCM model. This study would hopefully provide theoretical instructions for future land use planning and management, as well as a new methodology reference for LUCC analysis in arid and semiarid regions.

Identification of molecular markers associated with the progression and prognosis of endometrial cancer: a bioinformatic study.

BACKGROUND: Endometrial cancer (EC) is one kind of women cancers. Bioinformatic technology could screen out relative genes which made targeted therapy becoming conventionalized. METHODS: GSE17025 were downloaded from GEO. The genomic data and clinical data were obtained from TCGA. R software and bioconductor packages were used to identify the DEGs. Clusterprofiler was used for functional analysis. STRING was used to assess PPI information and plug-in MCODE to screen hub modules in Cytoscape. The selected genes were coped with functional analysis. CMap could find EC-related drugs that might have potential effect. Univariate and multivariate Cox proportional hazards regression analyses were performed to predict the risk of each patient. Kaplan-Meier curve analysis could compare the survival time. ROC curve analysis was performed to predict value of the genes. Mutation and survival analysis in TCGA database and UALCAN validation were completed. Immunohistochemistry staining from Human Protein Atlas database. GSEA, ROC curve analysis, Oncomine and qRT-PCR were also performed. RESULTS: Functional analysis showed that the upregulated DEGs were strikingly enriched in chemokine activity, and the down-regulated DEGs in glycosaminoglycan binding. PPI network suggested that NCAPG was the most relevant protein. CMap identified 10 small molecules as possible drugs to treat EC. Cox analysis showed that BCHE, MAL and ASPM were correlated with EC prognosis. TCGA dataset analysis showed significantly mutated BHCE positively related to EC prognosis. MAL and ASPM were further validated in UALCAN. All the results demonstrated that the two genes might promote EC progression. The profile of ASPM was confirmed by the results from immunohistochemistry. ROC curve demonstrated that the mRNA levels of two genes exhibited difference between normal and tumor tissues, indicating their diagnostic efficiency. qRT-PCR results supported the above results. Oncomine results showed that DNA copy number variation of MAL was significantly higher in different EC subtypes than in healthy tissues. GSEA suggested that the two genes played crucial roles in cell cycle. CONCLUSION: BCHE, MAL and ASPM are tumor-related genes and can be used as potential biomarkers in EC treatment.

Genome-wide bioinformatics analysis reveals CTCFL is upregulated in high-grade epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy that threatens the health of females. Previous studies have demonstrated that the survival outcomes of patients with different EOC grades varied. Therefore, the EOC grade is considered to serve as a distinctive prognostic factor. To date, the evaluation of ovarian cancer grade relies on pathological examination and a quantitative index for diagnosis is lacking. Furthermore, the dysregulation of genes has been demonstrated to exert pivotal functions in the carcinogenesis of EOCs. Therefore, the identification of effective biomarkers associated with EOC grade is of importance for the development of therapeutic regimens, and also contributes to the prediction of EOC prognosis. Microarrays have been increasingly applied for the identification of potential molecular biomarkers for numerous diseases including EOC. In the present study, four public microarray datasets (GSE26193, GSE63885, GSE30161 and GSE9891) were analyzed. A total of 6,103 upregulated probes corresponding to 5,766 genes, and 4,004 downregulated probes corresponding to 3,707 genes were identified in the GSE26193, GSE63885 and GSE30161 datasets. ALK and LTK ligand 2 was the most downregulated gene associated with the tumor grade, while CCCTC-binding factor like (CTCFL), EGF like domain multiple 6, radical S-adenosyl methionine domain containing 2 and SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 were the most upregulated genes associated with EOC grade. The GSE9891 dataset was added for further analysis. Only one probe (1552368_at) encoding for CTCFL was identified to be consistently upregulated in the four examined datasets. Immunohistochemical analysis was used to detect the expression of CTCFL between low- and high-grade EOC tissues and revealed that the EOC grade was closely associated with CTCFL level. This was corroborated via the reverse transcription-quantitative polymerase chain reaction. Taken together, the results of the present study suggested that CTCFL is upregulated in high-grade epithelial ovarian cancer.

Interleukin-35 Suppresses the Antitumor Activity of T Cells in Patients with Non-Small Cell Lung Cancer.

BACKGROUND/AIMS: Interleukin (IL)-35 has immunosuppressive functions in autoimmune diseases, infectious diseases, and certain cancers. However, few studies have focused on its immunoregulatory activity in non-small cell lung cancer (NSCLC). Thus, we investigated the role of IL-35 in the pathogenesis of this disease. METHODS: A total of 66 NSCLC patients and 21 healthy individuals were enrolled. IL-35 expression in peripheral blood and bronchoalveolar lavage fluid (BALF) was measured. The modulatory functions of IL-35 on purified CD4+ and CD8+ T cells from NSCLC patients were investigated in direct and indirect coculture systems with NSCLC cell lines. RESULTS: IL-35 expression was significantly increased in BALF from the tumor site, but not in the peripheral blood of NSCLC patients. IL-35 did not affect the bioactivity including proliferation, cytokine production, cell cycle, and cellular invasion of NSCLC cells. It suppressed responses from type 1 T helper (Th1) and Th17 cells but elevated the regulatory T cell response in cultured CD4+ T cells from NSCLC patients, and reduced cytokine-mediated CD4+ T cells cytotoxicity to NSCLC cells. Moreover, IL-35 also inhibited cytotoxic gene expression in CD8+ T cells from NSCLC, reducing their cytolytic and noncytolytic functions. CONCLUSION: The results of this study suggest that IL-35 contributes to the dysfunction/exhaustion of T cells and limited antitumor immune responses in NSCLC.

Synthesis and evaluation of novel water-soluble copolymers based on acrylamide and modular ß-cyclodextrin.

Mono-6-(allyl amino)-ß-cyclodextrin (N-ß-CD) and mono-2-O-(allyl oxygen radicals-2-hydroxyl propyl)-ß-cyclodextrin (O-ß-CD) were copolymerized with acrylamide (AM), acrylic acid (AA), and 1-llyl-3-oil acyloxyimidazole-1-ammonion bramide (AOAB) initiated by redox initiation system in an aqueous medium. The AM/AA/AOAB/N-ß-CD and AM/AA/AOAB/O-ß-CD were prepared by adjusting the reactive conditions, such as initiator concentration, pH, temperature, and monomer ratios. The obtained copolymers were characterized by means of infrared (IR) spectroscopy, (1)H NMR spectroscopy, scanning electron microscope (SEM), rotational rheometer, intrinsic viscosity, salt resistance, core flood test, etc. The temperature-tolerance, shear-tolerance, salt-resistance and thickening function of these copolymers are improved remarkably compared with partially hydrolyzed polyacrylamide (HPAM). About 18.3% and 12.5% oil recovery could be enhanced by 2000mg/L AM/AA/AOAB/N-ß-CD and AM/AA/AOAB/O-ß-CD comparing with water-flooding. In addition, the result of X-ray diffractometry (XRD) test showed that the solutions of obtained copolymers could remarkably reduce the crystalline interspace of sodium montmorillonite (from 18.9Å to 15.3Å).