Superoxide dismutases: marker in predicting reduced left ventricular ejection fraction in patients with type 2 diabetes and acute coronary syndrome.

AIM: To examine the prognostic value of superoxide dismutase (SOD) activity for monitoring reduced left ventricular ejection fraction(LVEF)in the patients with type 2 diabetes and acute coronary syndrome (ACS). METHODS: The population of this cross-sectional study included 2377 inpatients with type 2 diabetes who had an ACS admitted to the Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2016 to January 2021. RESULTS: Diabetic patients with ACS were divided into 2 subgroups based on LVEF. The mean SOD activity was significantly lower in patients with an LVEF ≤ 45% than in those with an LVEF > 45% (149.1 (146.4, 151.9) versus 161.9 (160.8, 163.0)). Using ROC statistic, a cut-off value of 148.8 U/ml indicated an LVEF ≤ 45% with a sensitivity of 51.6% and a specificity of 73.7%. SODs activity were found to be correlated with the levels of NT-proBNP, hs-cTnT, the inflammatory marker CRP and fibrinogen. Despite taking the lowest quartile as a reference (OR 0.368, 95% CI 0.493-0.825, P = 0.001) or examining 1 normalized unit increase (OR 0.651, 95% CI 0.482-0.880, P = 0.005), SOD activity was found to be a stronger predictor of reduced LVEF than CRP and fibrinogen, independent of confounding factors. CONCLUSIONS: Our cross-sectional study suggests that SOD activity might be a valuable and easily accessible tool for assessing and monitoring reduced LVEF in the diabetic patients with ACS.

Ubiquitous conservative interaction patterns between post-spliced introns and their mRNAs revealed by genome-wide interspecies comparison.

Introns, as important vectors of biological functions, can influence many stages of mRNA metabolism. However, in recent research, post-spliced introns are rarely considered. In this study, the optimal matched regions between introns and their mRNAs in nine model organism genomes were investigated with improved Smith-Waterman local alignment software. Our results showed that the distributions of mRNA optimal matched frequencies were highly consistent or universal. There are optimal matched frequency peaks in the UTR regions, which are obvious, especially in the 3'-UTR. The matched frequencies are relatively low in the CDS regions of the mRNA. The distributions of the optimal matched frequencies around the functional sites are also remarkably changed. The centers of the GC content distributions for different sequences are different. The matched rate distributions are highly consistent and are located mainly between 60% and 80%. The most probable value of the optimal matched segments is about 20 bp for lower eukaryotes and 30 bp for higher eukaryotes. These results show that there are abundant functional units in the introns, and these functional units are correlated structurally with all kinds of sequences of mRNA. The interaction between the post-spliced introns and their corresponding mRNAs may play a key role in gene expression.

A clinical observation study on the effect of needle-free insulin syringe on blood glucose control and well-being index in patients with early-onset type 2 diabetes mellitus.

Objective: To explore the effect of using needle-free insulin syringe on blood sugar control and well-being index in patients with early-onset type 2 diabetes mellitus. Methods: A total of 42 patients with early-onset type 2 diabetes mellitus treated with insulin aspart 30 injection in a stable condition in the Endocrinology Department of a tertiary hospital from January 2020 to July 2021 were randomly divided into two groups, one group received insulin pen injections followed by needle-free injections, and the other group received needle-free injections followed by insulin pen injections. Transient scanning glucose monitoring was performed during the last two weeks of each injection modality phase. Comparison of the two injection methods in terms of test indicators and differences in injection site pain scores, the number of red spots on the skin at the injection site and the number of bleeding spots on the skin at the injection site. Results: The FBG of the needle-free injection group was lower than that of the Novo Pen group (p<0.05); the 2-hour postprandial blood glucose of the needle-free injection group was lower than that of the Novo Pen group, but there was no statistical significant difference. The amount of Insulin in the needle-free injector group was lower than that in the Novo pen group, but there was no statistical significant difference between the two groups. The WHO-5 score of the needle-free injector group was higher than that of the Novo Pen group(p<0.05); the pain score at the injection site was lower than that of the Novo Pen group (p<0.05). The number of skin red spots using the needle-free syringe was more than that of the Novo pen group(p<0.05); the number of skin bleeding at the site of injection was similar between the two injection methods. Conclusion: Compared to traditional insulin pens, subcutaneous injection of premixed insulin using a needle-free syringe is effective in controlling fasting blood glucose in patients with early onset type 2 diabetes and is less painful at the injection site. In addition, blood glucose monitoring should be strengthened and insulin dosage should be adjusted in a timely manner.

A novel approach to analyze the association characteristics between post-spliced introns and their corresponding mRNA.

Studies have shown that post-spliced introns promote cell survival when nutrients are scarce, and intron loss/gain can influence many stages of mRNA metabolism. However, few approaches are currently available to study the correlation between intron sequences and their corresponding mature mRNA sequences. Here, based on the results of the improved Smith-Waterman local alignment-based algorithm method (SW method) and binding free energy weighted local alignment algorithm method (BFE method), the optimal matched segments between introns and their corresponding mature mRNAs in Caenorhabditis elegans (C.elegans) and their relative matching frequency (RF) distributions were obtained. The results showed that although the distributions of relative matching frequencies on mRNAs obtained by the BFE method were similar to the SW method, the interaction intensity in 5'and 3'untranslated regions (UTRs) regions was weaker than the SW method. The RF distributions in the exon-exon junction regions were comparable, the effects of long and short introns on mRNA and on the five functional sites with BFE method were similar to the SW method. However, the interaction intensity in 5'and 3'UTR regions with BFE method was weaker than with SW method. Although the matching rate and length distribution shape of the optimal matched fragment were consistent with the SW method, an increase in length was observed. The matching rates and the length of the optimal matched fragments were mainly in the range of 60%-80% and 20-30bp, respectively. Although we found that there were still matching preferences in the 5'and 3'UTR regions of the mRNAs with BFE, the matching intensities were significantly lower than the matching intensities between introns and their corresponding mRNAs with SW method. Overall, our findings suggest that the interaction between introns and mRNAs results from synergism among different types of sequences during the evolutionary process.

Identification and Characterization of Two Novel Compounds: Heterozygous Variants of Lipoprotein Lipase in Two Pedigrees With Type I Hyperlipoproteinemia.

Background: Type I hyperlipoproteinemia, characterized by severe hypertriglyceridemia, is caused mainly by loss-of-function mutation of the lipoprotein lipase (LPL) gene. To date, more than 200 mutations in the LPL gene have been reported, while only a limited number of mutations have been evaluated for pathogenesis. Objective: This study aims to explore the molecular mechanisms underlying lipoprotein lipase deficiency in two pedigrees with type 1 hyperlipoproteinemia. Methods: We conducted a systematic clinical and genetic analysis of two pedigrees with type 1 hyperlipoproteinemia. Postheparin plasma of all the members was used for the LPL activity analysis. In vitro studies were performed in HEK-293T cells that were transiently transfected with wild-type or variant LPL plasmids. Furthermore, the production and activity of LPL were analyzed in cell lysates or culture medium. Results: Proband 1 developed acute pancreatitis in youth, and her serum triglycerides (TGs) continued to be at an ultrahigh level, despite the application of various lipid-lowering drugs. Proband 2 was diagnosed with type 1 hyperlipoproteinemia at 9 months of age, and his serum TG levels were mildly elevated with treatment. Two novel compound heterozygous variants of LPL (c.3G>C, p. M1? and c.835_836delCT, p. L279Vfs*3, c.188C>T, p. Ser63Phe and c.662T>C, p. Ile221Thr) were identified in the two probands. The postheparin LPL activity of probands 1 and 2 showed decreases of 72.22 ± 9.46% (p<0.01) and 54.60 ± 9.03% (p<0.01), respectively, compared with the control. In vitro studies showed a substantial reduction in the expression or enzyme activity of LPL in the LPL variants. Conclusions: Two novel compound heterozygous variants of LPL induced defects in the expression and function of LPL and caused type I hyperlipoproteinemia. The functional characterization of these variants was in keeping with the postulated LPL mutant activity.

SINR-based power schedule of sensors and DoS attackers in wireless network.

In this paper, the game theory approaches are used to solve the power schedule problem in the wireless communication network. All sensors can be affected by DoS attackers when transmitting data. The game process between sensors and attackers is established as Bayesian game process. First, a Nash Equilibrium (NE) framework is proposed based on the object function consist of signal-to-interference-and-noise-ratio (SINR). Second, the total power of sensors is considered to have two types, and each type has some power levels. Unlike NE, both sensors and attackers no longer learn the specific total power of each other. However, sensors and attackers can get the type distribution of each other. In this situation, the strategies of sensors and attackers are formulated by introducing the Harsanyi transformation, and the Bayesian Nash Equilibrium (BNE) is solved. Finally, the Bayesian equilibrium strategies used by both offensive and defensive players are compared in the numerical example, which can illustrate the advantage of making full use of incomplete information.

Electroacupuncture Attenuates Immune-Inflammatory Response in Hippocampus of Rats with Vascular Dementia by Inhibiting TLR4/MyD88 Signaling Pathway.

OBJECTIVE: To investigate whether electroacupuncture (EA) alleviates cognitive impairment by suppressing the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia (VaD). METHODS: The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table, including sham, four-vessel occlusion (4-VO), 4-VO+EA, 4-VO+non-EA, sham+EA, 4-VO+lipopolysaccharide (LPS), 4-VO+LPS+EA, and 4-VO+TAK-242 groups. The VaD model was established by the 4-VO method. Seven days later, rats were treated with EA at 5 acupoints of Baihui (DV 20), Danzhong (RN 17), Geshu (BL 17), Qihai (RN 6) and Sanyinjiao (SP 6), once per day for 3 consecutive weeks. Lymphocyte subsets, lymphocyte transformation rates, and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α(TNF-α) were measured to assess immune function and inflammation in VaD rats. Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus. The levels of TLR4, MyD88, IL-6, and TNF-α were detected after EA treatment. TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA. RESULTS: Compared with the 4-VO group, EA notably improved immune function of rats in the 4-VO+EA group, inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats, reduced the expressions of serum IL-6 and TNF-α (all P<0.05 or P<0.01), and led to neuronal repair in the hippocampus. There were no significant differences between the 4-VO+LPS+EA and 4-VO+EA groups, nor between the 4-VO+TAK-242 and 4-VO+EA groups (P>0.05). CONCLUSIONS: EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway. Thus, EA may be a promising alternative therapy for the treatment of VaD.

Characteristics of Postoperative Pain After VATS and Pain-Related Factors: The Experience in National Cancer Center of China.

PURPOSE: No final conclusion has yet been reached on characteristics of postoperative pain and pain-related factors after video-assisted thoracoscopic surgery (VATS). This study was designed to explore features of acute severe pain and chronic post-surgical pain (CPSP), and the pain-related factors of VATS. PATIENTS AND METHODS: Data of patients who underwent VATS for lung cancer in Cancer Hospital, Chinese Academy of Medical Sciences between March 2017 and January 2019 were reviewed in this retrospective study. A numerical rating scale (NRS) was used for evaluating the intensity of postoperative pain including no pain (NRS=0), mild pain (NRS=1-3), moderate pain (NRS=4-6), and severe pain (NRS=7-10). Pain intensity was assessed daily within a week after operation, and also evaluated at 3 months postoperatively. RESULTS: One hundred and five (3.4%) of the 3072 patients enrolled experienced severe pain (NRS=7-10) on the 1st day after operation, and 17 (0.6%) on the 2nd day. Smoking history, three-port VATS, prolonged operation time, and without patient-controlled analgesia (PCA) were correlated to increased incidence of severe pain. Among all patients, 237 (7.7%) cases generated CPSP, and VATS type, operation time, duration of drainage, and severe pain on the 1st day were four independent risk factors related to CPSP. CONCLUSION: Patients seemed to experience a lower incidence of acute severe pain and CPSP after VATS than traditional open surgery. Acute severe pain was correlated with smoking history, VATS type, operation time, and PCA; VATS type, operation time, duration of drainage, and severe pain on the 1st day postoperatively were four independent risk factors of CPSP.

Health-related quality of life of type 2 diabetes patients hospitalized for a diabetes-related complication.

PURPOSE: To estimate the health-related quality of life (HRQoL) of type 2 diabetes (T2DM) inpatients hospitalized for a complication in China and to explore the associated factors. METHODS: This was a cross-sectional study. T2DM inpatients (aged ≥ 18 years) hospitalized for a complication, including ischemic heart disease (IHD), acute myocardial infarction (AMI), congestive heart failure (CHF), stroke, impaired vision, end-stage renal disease (ESRD), ulcer, and amputation were recruited from a tertiary hospital in China from January to May 2017. The EuroQoL-5 dimensions were used to measure HRQoL. A one-way analysis of variance and a multivariate regression analysis were performed. RESULTS: Eight hundred and two T2DM inpatients hospitalized for a complication were included. The mean age was 62.67 years, and 43% of the inpatients were female. The mean utility-based HRQoL was 0.562 (95% CI 0.548, 0.577). The utility varied significantly between the complications: IHD = 0.620 (95% CI 0.597, 0.642), AMI = 0.434 (95% CI 0.394, 0.473), CHF = 0.471 (95% CI 0.433, 0.510), stroke = 0.472 (95% CI 0.436, 0.508), impaired vision = 0.714 (95% CI 0.692, 0.737), ESRD = 0.693 (95% CI 0.670, 0.717), ulcer = 0.431 (95% CI 0.375, 0.487), and amputation = 0.395 (95% CI 0.341, 0.448). Inpatients with a complication, who were female, and who had no daily exercise had a lower HRQoL. CONCLUSIONS: The HRQoL of T2DM inpatients with a complication was considerably impaired. Our estimates provide supplementary data for public health and cost-effectiveness modeling, and increase the breadth of knowledge of HRQoL in T2DM.

Apatinib suppresses the Proliferation and Apoptosis of Gastric Cancer Cells via the PI3K/Akt Signaling Pathway.

PURPOSE: To observe the mechanism of the effects of Apatinib on the proliferation and apoptosis of human gastric cancer (HGC-27) cells via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway through in vitro cytology experiments. METHODS: The human gastric cancer HGC-27 cell line was taken as the research object, and LY294002, an inhibitor of the PI3K/Akt signaling pathway, as the positive control. The experimental methods are as follows: (1) The proliferation of HGC-27 cells inhibited by Apatinib and LY294002 was observed by 3-(4,5)-dimethylthiahiazo-(z-y1)-3,5-diphenytetrazoli- umromide (MTT) assay; (2) flow cytometry was adopted to detect the apoptosis of cells after they were treated with drugs and the positive control; (3) different effects of varying concentrations of Apatinib on apoptosis-related genes and proteins, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and cysteine-aspartic acid protease (Caspase) 9, were detected via fluorescence quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting (WB), and the effects of different concentrations of Apatinib on the protein expressions of PI3K, phosphorylated (p)-PI3K, Akt and p-Akt were detected by Western blotting. RESULTS: (1) MTT results showed that Apatinib could effectively inhibit the proliferation of HGC-27 cells in a dose-dependent manner. (2) Flow cytometry results manifested that Apatinib could induce the apoptosis of HGC-27 cells. (3) The results of qRT-PCR and Western blotting demonstrated that apatinib was capable of inducing the expression of the pro-apoptotic genes, Bax and Caspase 9, and inhibit the expression of the anti-apoptotic gene Bcl-2. The final results of Western blotting confirmed that Apatinib could decrease the protein expression levels of p-PI3K and p-Akt, thus inhibiting the phosphorylation of the PI3K/Akt pathway. CONCLUSIONS: The experiment proves that Apatinib can effectively suppress the proliferation and induce the apoptosis of human gastric cancer HGC-27 cells, the mechanism of which is related to the inhibition on phosphorylation of the PI3K/Akt signaling pathway.

Gongronella sp. w5 elevates Coprinopsis cinerea laccase production by carbon source syntrophism and secondary metabolite induction.

When sucrose was used as the carbon source, the Basidiomycete Coprinopsis cinerea showed poor growth and low laccase activity in pure culture, but greatly enhanced the level of laccase activity (>1800 U/L) during coculture with the Mucoromycete Gongronella sp. w5. As a result, the mechanism of laccase overproduction in coculture was investigated by starting from clarifying the function of sucrose. Results demonstrated that Gongronella sp. w5 in the coculture system hydrolyzed sucrose to glucose and fructose by an intracellular invertase. Fructose rather than glucose was supplied by Gongronella sp. w5  as the readily available carbon source for C. cinerea, and contributed to an alteration of its growth behavior and a basal laccase secretion of 110.6 ± 3.3 U/L. On the other hand, separating Gongronella sp. w5 of C. cinerea by transfer into dialysis tubes yielded the same level of laccase activity as without separation, indicating that enhanced laccase production probably resulted from the metabolites in the fermentation broth. Further investigation showed that the ethyl acetate-extracted metabolites generated by Gongronella sp. w5 induced C. cinerea laccase production. One of the laccase-inducing compounds namely p-hydroxybenzoic acid (HBA) was purified and identified from the extract. When using HBA as the inducer and fructose as the carbon source in monoculture, C. cinerea observed similar high laccase activity to that in coculture, and zymograms revealed the same expression of laccase Lcc9 as the main and Lcc1 and Lcc5 as the minor enzymes. Overall, our experiments verified that Gongronella sp. w5 elevates Coprinopsis cinerea laccase production by carbon source syntrophism and secondary metabolite induction.

Complete genome of Gongronella sp. w5 provides insight into its relationship with plant.

Gongronella sp. w5 (w5) is a soil fungus isolated from Anhui, China. Here we report the high-quality genome sequence of w5 and its phenotypic characteristics based on genomic information. The genome of w5 consists of 34,723,828 bp assembled into 149 scaffolds and 11,302 predicted protein-coding genes. Genome analysis suggested that w5 may possess host cell infection capacity and maybe a biotrophic fungus that relies on plant sucrose as carbon source. W5 shows the ability of rapid invasion into the plant root cells based on CAZymes analysis. Further results evidenced that w5 can use sucrose as the carbon source. Plant inoculation revealed that w5 penetrates the root cells of Actinidia chinensis with its hypha, and simultaneously promotes plant growth. It may promote plant growth by secreting organic acid and facilitating phosphate acquisition. The new genomic data and phenotype features will facilitate future applications of this strain in biotechnology.

Dual silencing of EGFR and HER2 enhances the sensitivity of gastric cancer cells to gefitinib.

Gefitinib exhibits very limited efficacy in gastric cancer (GC). Indeed, the limited clinical results obtained with gefitinib alone justify investigation of additional therapeutic strategies. Here, we demonstrate the importance of EGFR and HER2 in GC malignancy using RNA interference (RNAi). Additionally, we explored the ability of RNAi targeting EGFR and HER2 to enhance the sensitivity of GC cells to gefitinib. Specific small interfering RNAs (siRNAs) significantly inhibited mRNA and protein expression of target genes. EGFR-specific siRNA, EGFR/HER2 siRNAs, and gefitinib inhibited growth and induced apoptosis in GC cell lines in a dose-dependent manner. In contrast, resistance to HER2-siRNA-induced growth inhibition and apoptosis was linked to compensatory activation of EGFR. Moreover, gefitinib dramatically reduced p-EGFR and p-HER2 levels in the cell lines tested, and sensitivity to gefitinib was enhanced through dual silencing of EGFR and HER2 via suppression of AKT and ERK activation. These findings are in agreement with the profound inhibitory effect of gefitinib on activation of both EGFR and HER2. Overall, EGFR/HER2 knockdown by siRNAs further decreased the growth of GC cells treated with gefitinib alone, confirming that single-agent drug targeting does not achieve a maximal biological effect. The combination of gefitinib with EGFR/HER2 siRNAs should be further investigated as a new strategy for the treatment of GC and other EGFR/HER2-dependent cancers.

High glucose increases LPS-induced DC apoptosis through modulation of ERK1/2, AKT and Bax/Bcl-2.

BACKGROUND: This study investigates the effect of glucose on the LPS-induced apoptosis of dendritic cells in the intestinal tract of mice and the dendritic cell line DC2.4. METHODS: Flow cytometry was used to detect dendritic cell apoptosis both in vivo and in vitro. Hoechst 33258 staining was used to detect the morphological changes characteristic of apoptotic nuclei. Expression of apoptosis related proteins was investigated by western blot analysis and immunohistochemistry. RESULTS: Pretreatment with a high concentration of glucose increased apoptosis of LPS-treated dendritic cells both in vivo and in vitro at 24 h. No effect was evident at the earlier time points of 15 min and 6 h in vitro. Furthermore, at 24 hours the expression of the survival proteins AKT, ERK and Bcl-2 was decreased, while the expression of the proapoptotic protein Bax was increased. AKT, ERK, Bcl-2 and Bax were mainly located in the cytoplasm by immunohistochemistry. CONCLUSIONS: These results suggest that high glucose concentrations might prime dendritic cells for apoptosis induced by LPS in the intestinal tract through upregulating the expression of Bax and downregulating the expression of AKT, ERK and Bcl-2. Therefore, this study may give clues to understanding the immunological mechanism behind gastrointestinal complications in diabetes mellitus.

GO-COO-HP-ß-CD nanosphere: a complex construction and its drug-loading properties.

A novel nanosphere based on carboxylated GO (GO-COOH) and hydroxypropyl-beta-CD (HP-ß-CD) was synthesized to construct a complex of GO-COO-HP-ß-CD. The complex formation process was studied using spectral characterization and transmission electron microscopy (TEM). X-ray diffraction and energy dispersive spectroscopy patterns show that HP-ß-CD molecules either cover or intercalate into GO-COOH interlayers in the complex. Fourier transform infrared spectroscopy results indicate that GO-COOH and HP-ß-CD are linked with covalent bonds formed via esterification. When employed as nanohybrid drug carriers for dexamethasone, the inclusion displays good dispersibility validated by dynamic light scattering (DLS). Cytotoxicity assays and hemolysis testing demonstrate that the nanospheres possess good biological compatibility. The loading capacity of dexamethasone is as high as 32.33%, with loading efficiency 64.66%.

Effects of periodontal treatment on glycemic control in type 2 diabetic patients: a meta-analysis of randomized controlled trials.

The association between diabetes and inflammatory periodontal diseases has been studied extensively. However, there is a lack of robustness and homogeneity among studies describing effects of periodontal treatment on glycemic control. The aim of this study was to carry out a meta-analysis to understand whether periodontal treatment could improve glycemic control in type 2 diabetic patients. Electronic searches were carried out on MEDLINE, EMBASE and the Cochrane central register of controlled trials from 1980 to July 2012. Randomized controlled trials of periodontal therapy on glycemic control in diabetic patients with a minimum of 3 months of follow-up were included. Meta-analysis was carried out with 8 studies involving 515 participants using Stata 11.0 software. Our results showed that periodontal treatment could lead to a significant decrease in HbA1c level. The standardized mean difference between intervention groups and control groups was significant: 1.03% (95% confidence interval: 0.31% to 1.70%, P = 0.003) from baseline to 3 months, and 1.18% (95% confidence interval: 0.72% to 1.64%, P < 0.001) from baseline to 6 months. Periodontal treatment could lead to a non-significant decrease in fasting plasma glucose (FPG) levels from baseline to 3 months. The standardized mean difference between the intervention and the control group was 0.69 mg/dl (95% confidence interval: -0.27 mg/dl to 1.66 mg/dl, P = 0.158). Our analysis indicated that periodontal treatment could improve glycemic control in type 2 diabetic patients with periodontal diseases.