Microarray Expression Profile of Exosomal circRNAs from High Glucose Stimulated Human Renal Tubular Epithelial Cells.

Introduction: Circular RNA (circRNAs) are a type of non-coding RNA (ncRNAs) with a wealth of functions. Recently, circRNAs have been identified as important regulators of diabetic kidney disease (DKD), owing to their stability and enrichment in exosomes. However, the role of circRNAs in exosomes of tubular epithelial cells in DKD development has not been fully elucidated. Methods: In our study, microarray technology was used to analyze circRNA expression in cell supernatant exosomes isolated from HK-2 cells with or without high glucose (HG) treatment. The small interfering RNAs (siRNA) and plasmid overexpression were used to validate functions of differentially expressed circRNAs. Results: We found that exosome concentration was higher in HG-stimulated HK-2 cells than in controls. A total of 235 circRNAs were significantly increased and 458 circRNAs were significantly decreased in the exosomes of the HG group. In parallel with the microarray data, the qPCR results showed that the expression of circ_0009885, circ_0043753, and circ_0011760 increased, and the expression of circ_0032872, circ_0004716, and circ_0009445 decreased in the HG group. Rescue experiments showed that the effects of high glucose on regulation of CCL2, IL6, fibronetin, n cadherin, e cadherin and epcam expression can be reversed by inhibiting or overexpressing these circRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses indicated that circRNA parental genes are associated with glucose metabolism, lipid metabolism, and inflammatory processes, which are important in DKD development. Further analysis of circRNA/miRNA interactions indicated that 152 differentially expressed circRNAs with fold change (FC) ≥1.5 could be paired with 43 differentially expressed miRNAs, which are associated with diabetes or DKD. Discussion: Our results indicate that exosomal circRNAs may be promising diagnostic and therapeutic biomarkers, and may play a critical role in the progression of DKD.

Laparoscopic vs. open distal gastrectomy for locally advanced gastric cancer: A systematic review and meta-analysis of randomized controlled trials.

Objective: The aim of this systematic review and meta-analysis is to compare the short- and long-term outcomes of laparoscopic distal gastrectomy (LDG) with those of open distal gastrectomy (ODG) for patients with advanced gastric cancer (AGC) who exclusively underwent distal gastrectomy and D2 lymphadenectomy in randomized controlled trials (RCTs). Background: Data in published meta-analyses that included different gastrectomy types and mixed tumor stages prevented an accurate comparison between LDG and ODG. Recently, several RCTs that compared LDG with ODG included AGC patients specifically for distal gastrectomy, with D2 lymphadenectomy being reported and updated with the long-term outcomes. Methods: PubMed, Embase, and Cochrane databases were searched to identify RCTs for comparing LDG with ODG for advanced distal gastric cancer. Short-term surgical outcomes and mortality, morbidity, and long-term survival were compared. The Cochrane tool and GRADE approach were used for evaluating the quality of evidence (Prospero registration ID: CRD42022301155). Results: Five RCTs consisting of a total of 2,746 patients were included. Meta-analyses showed no significant differences in terms of intraoperative complications, overall morbidity, severe postoperative complications, R0 resection, D2 lymphadenectomy, recurrence, 3-year disease-free survival, intraoperative blood transfusion, time to first liquid diet, time to first ambulation, distal margin, reoperation, mortality, or readmission between LDG and ODG. Operative times were significantly longer for LDG [weighted mean difference (WMD) 49.2 min, p < 0.05], whereas harvested lymph nodes, intraoperative blood loss, postoperative hospital stay, time to first flatus, and proximal margin were lower for LDG (WMD -1.3, p < 0.05; WMD -33.6 mL, p < 0.05; WMD -0.7 day, p < 0.05; WMD -0.2 day, p < 0.05; WMD -0.4 mm, p < 0.05). Intra-abdominal fluid collection and bleeding were found to be less after LDG. Certainty of evidence ranged from moderate to very low. Conclusions: Data from five RCTs suggest that LDG with D2 lymphadenectomy for AGC has similar short-term surgical outcomes and long-term survival to ODG when performed by experienced surgeons in hospitals contending with high patient volumes. It can be concluded that RCTs should highlight the potential advantages of LDG for AGC. Systematic Review Registration: PROSPERO, registration number CRD42022301155.

Ultrafast dynamic switching of optical response based on nonlinear hyperbolic metamaterial platform.

The pursuit of high-speed and on-chip optical communication systems has promoted extensive exploration of all-optical control of light-matter interactions via nonlinear optical processes. Here, we have numerically investigated the ultrafast dynamic switching of optical response using tunable hyperbolic metamaterial (HMM) which consists of five pairs of alternating layers of indium tin oxide (ITO) and SiO2. The nonlinearity of the HMM is analyzed by the ultrafast dynamics of the hot electrons in the epsilon-near-zero (ENZ) ITO. Our approach allows large and broad all-optical modulation of the effective permittivity and topology of the HMM on the femtosecond time-scale. Based on the proposed HMM platform, we have shown considerable tunability in the extinction ratio and Purcell enhancement under various pump fluence. In addition, we have achieved all-optical control of the coupling strength through depositing plasmonic resonators on the HMM platform. A significant tuning of the coupled resonance is observed by changing pump fluence, which leads to a switching time within 213 fs at a specific wavelength with a relative modulation depth more than 15 dB.

Ultrafast dynamic switching of optical response based on nonlinear hyperbolic metamaterial platform: erratum.

We present an erratum to our previously published work ["Ultrafast dynamic switching of optical response based on nonlinear hyperbolic metamaterial platform," Opt. Express30(12), 21634 (2022).10.1364/OE.457875]. The corrections do not affect the results and conclusion of the original paper.

All-optical switching in epsilon-near-zero asymmetric directional coupler.

We propose an all-optical switch based on an asymmetric directional coupler structure with epsilon-near-zero (ENZ) layer. The nonlinear optical properties the of ENZ layer are analyzed by hot-electron dynamics process, and the all-optical operating performance of the switch on the silicon nitride platform is investigated. It is found that the pump-induced refractive index change in ENZ layer gives rise to a transfer of signal light in the optical system. We demonstrate that the proposed switch design features an insertion loss of < 2.7 dB, low crosstalk of < - 18.93 dB, and sub-pico-second response time at the communication wavelength of 1.55 µm. With ultrafast response, high performance, and simple structure, the device provides new possibilities for all-optical communication and signal processing.

A rare case with multiple arterial variations of the liver complicated laparoscopic pancreaticoduodenectomy.

BACKGROUND: Hepatic arterial variations were fully elaborated in anatomical monographs. Here, we aimed to present a rare case with multiple arterial variations of the liver complicated laparoscopic pancreaticoduodenectomy. CASE PRESENTATION: We report a 67-year-old woman with a periampullary tumor underwent laparoscopic pancreaticoduodenectomy. Intraoperatively, the aberrant right hepatic artery derived from the gastroduodenal artery (GDA) was observed and had accidentally sacrificed due to untimely ligature of GDA. Three-dimensional reconstruction based on preoperative contrast-enhanced CT performed to better study the anatomy. It demonstrated a replaced right hepatic artery branched from the GDA and supplied right liver lobe. Meanwhile, the middle hepatic artery derived from the common hepatic artery and supplied hepatic segment IV. Additionally, the replaced left hepatic artery emerged from the left gastric artery and fed into left liver lobe. CONCLUSIONS: The origination and course of hepatic arterial anatomy should be thoroughly assessed in planning and performing hepatopancreatobiliary surgeries. Reconstruction images of contrast-enhanced CT are helpful to visualize the vascular variations and its spatial relation with adjacent structures.

One-stage versus two-stage management for acute cholecystitis associated with common bile duct stones: a retrospective cohort study.

BACKGROUND: Both one-stage [laparoscopic cholecystectomy (LC) plus laparoscopic common bile duct exploration (LCBDE)] and two-stage [endoscopic retrograde cholangiopancreatography (ERCP) followed by sequential LC] approaches are effective treatment for concomitant common bile duct (CBD) stones and gallstone. Although many studies compared one-stage with two-stage surgical approach for cholecysto-choledocholithiasis, there are very few studies compared the two management strategies for acute cholecystitis (AC) associated with CBD stones. METHODS: Between January 2014 and December 2019, patients with concomitant AC and CBD stones proposed to early surgery were retrospectively studied. The patients were scheduled to undergo either the one-stage [LCBDE and LC (LCBDE+LC) were undertaken at the same operation] or two-stage [preoperative ERCP for CBD stone clearance was followed by LC 1-3 days later (pre-ERCP+LC)] procedure. The success rate of complete stone clearance, procedure-related complication, hospital stay, hospitalization charges and later biliary complications were compared between the two groups. RESULTS: Sixty patients were included in the study, 28 in the one-stage group and 32 in the two-stage group. There was no significant difference in the success rate of complete stone clearance (96.4% vs. 93.8%, P = 1.000), complication rate (10.7% vs. 9.4%, P = 1.000), incidence of pancreatitis (0 vs. 6.3%, P = 0.494) or length of hospital stay (12 ± 5 vs. 11 ± 4 days, P = 0.393) between the two groups. CONCLUSION: For patients with concomitant AC and choledocholithiasis proposed to early surgery, both the one-stage (LCBDE+LC) and two-stage (pre-ERCP+LC) approaches were acceptable and broadly comparable in achieving clearance of CBD stones.

Laparoscopic versus open pancreaticoduodenectomy for pancreatic and periampullary tumor: A meta-analysis of randomized controlled trials and non-randomized comparative studies.

Objective: This meta-analysis compares the perioperative outcomes of laparoscopic pancreaticoduodenectomy (LPD) to those of open pancreaticoduodenectomy (OPD) for pancreatic and periampullary tumors. Background: LPD has been increasingly applied in the treatment of pancreatic and periampullary tumors. However, the perioperative outcomes of LPD versus OPD are still controversial. Methods: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched to identify randomized controlled trials (RCTs) and non-randomized comparative trials (NRCTs) comparing LPD versus OPD for pancreatic and periampullary tumors. The main outcomes were mortality, morbidity, serious complications, and hospital stay. The secondary outcomes were operative time, blood loss, transfusion, postoperative pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH), bile leak (BL), delayed gastric emptying (DGE), lymph nodes harvested, R0 resection, reoperation, and readmission. RCTs were evaluated by the Cochrane risk-of-bias tool. NRCTs were assessed using a modified tool from the Methodological Index for Non-randomized Studies. Data were pooled as odds ratio (OR) or mean difference (MD). This study was registered at PROSPERO (CRD42022338832). Results: Four RCTs and 35 NRCTs concerning a total of 40,230 patients (4,262 LPD and 35,968 OPD) were included. Meta-analyses showed no significant differences in mortality (OR 0.91, p = 0.35), serious complications (OR 0.97, p = 0.74), POPF (OR 0.93, p = 0.29), PPH (OR 1.10, p = 0.42), BL (OR 1.28, p = 0.22), harvested lymph nodes (MD 0.66, p = 0.09), reoperation (OR 1.10, p = 0.41), and readmission (OR 0.95, p = 0.46) between LPD and OPD. Operative time was significantly longer for LPD (MD 85.59 min, p < 0.00001), whereas overall morbidity (OR 0.80, p < 0.00001), hospital stay (MD -2.32 days, p < 0.00001), blood loss (MD -173.84 ml, p < 0.00001), transfusion (OR 0.62, p = 0.0002), and DGE (OR 0.78, p = 0.002) were reduced for LPD. The R0 rate was higher for LPD (OR 1.25, p = 0.001). Conclusions: LPD is associated with non-inferior short-term surgical outcomes and oncologic adequacy compared to OPD when performed by experienced surgeons at large centers. LPD may result in reduced overall morbidity, blood loss, transfusion, and DGE, but longer operative time. Further RCTs should address the potential advantages of LPD over OPD. Systematic review registration: PROSPERO, identifier CRD42022338832.

Corrigendum: Correlation of Long Non-coding RNA LncRNA-FA2H-2 With Inflammatory Markers in the Peripheral Blood of Patients With Coronary Heart Disease.

[This corrects the article DOI: 10.3389/fcvm.2021.682959.].

Correlation of Long Non-coding RNA LncRNA-FA2H-2 With Inflammatory Markers in the Peripheral Blood of Patients With Coronary Heart Disease.

Objective: To characterize the expression of long non-coding RNA LncRNA-FA2H-2 in coronary heart disease (CHD) and its correlation with inflammatory markers. Methods: From December 2018 to December 2020, 316 patients at Henan Provincial People's Hospital who complained of chest tightness or chest pain and had coronary angiography to clarify their coronary artery conditions for definitive diagnoses were selected as the study subjects. Plasma was collected to detect white blood cells (WBCs), total cholesterol (TG), triglyceride cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), and C-reactive protein (CRP) levels. Tumor necrosis factor (TNF-α), monocyte chemotactic protein 1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and interleukin-6 (IL-6) levels were also measured using ELISA. The expression levels of lncRNA-FA2H-2 were measured using quantitative real-time PCR. The data obtained were analyzed by independent sample t-tests, rank sum tests, regression analyses, Pearson's or Spearman's correlation analyses, and receiver operating characteristic curves. Results: (1) Compared with the control group, the differences in age, sex, diabetes, smoking, drinking, body mass index (BMI), WBC, TC, and LDL-C in CHD were not statistically significant, while the differences in hypertension, TG, HDL-C, ApoA1, and CRP were statistically significant. (2) In the grouping of coronary lesion branches, patients with age, sex, hypertension, diabetes, smoking, drinking, BMI, WBC, TC, LDL-C, HDL-C, and ApoA1 differences were not statistically significant, but TG and CRP differences were statistically significant. (3) The relative expressions of TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 were significantly upregulated in the CHD group (P < 0.001). (4) The results showed that the relative levels of TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 between the two comparative analyses (high risk, moderate risk, and low risk groups) were statistically significant. In addition, positive correlations were found between the Gensini score and TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 in CHD patients. (5) LncRNA-FA2H-2 relative expression in the CHD group was significantly downregulated (P < 0.001). (6) The differences in the expression levels of LncRNA-FA2H-2 were statistically significant between the two comparative analyses (P < 0.01), except between the 2-branch lesion and 3-branch lesion groups. (7) LncRNA-FA2H-2 was not associated with age, sex, hypertension, diabetes, smoking, drinking, BMI, WBC, TG, TC, LDL-C, HDL-C, and ApoA1 (P > 0.05). (8) A correlation was found between LncRNA-FA2H-2 and MCP-1, and VCAM-1, ICAM-1, IL-6, and Gensini. (9) The results indicated that the relative levels of LncRNA-FA2H-2 between the two comparative analyses (high risk, moderate risk, and low risk groups) were statistically significant. A negative correlation was found between the Gensini score and LncRNA-FA2H-2. (10) ROC curve analyses of TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 in CHD showed the area under the curve (AUC) = 0.832 (0.77, 0.893) with a cut-off value of 290.5, a sensitivity of 73%, and a specificity of 64%; AUC = 0.731 (0.653, 0.809) with a cut-off value of 396 and with a sensitivity of 59% and specificity of 79%; AUC = 0.822 (0.757, 0.887) with a cut-off value of 264 and with a sensitivity of 72% and specificity of 83%; AUC = 0.794 (0.715, 0.874) with a cut-off value of 201.5 and with a sensitivity of 75% and specificity of 65%; AUC = 0.760 (0.685, 0.834) with a cut-off value of 328 and with a sensitivity of 55% and specificity of 90%. (11) ROC curve analysis of LncRNA-FA2H-2 in CHD patients showed AUC = 0.834 (0.688, 0.85) with a cut-off value of 3.155 and with a sensitivity of 85% and specificity of 82%. (12) Logistic analyses showed that TNF-α, MCP-1, VCAM-1, IL-6, and LncRNA-FA2H-2 were independent risk factors for CHD. Conclusions: The expression of LncRNA-FA2H-2 was reduced and inversely correlated with inflammation-related factors in CHD patients. LncRNA-FA2H-2 may have potential as an inflammatory marker for risk assessment of CHD development.

Comparative Performance of Four Nucleic Acid Amplification Tests for SARS-CoV-2 Virus.

BACKGROUND: COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was discovered in 2019 and spread around the world in a short time. SARS-CoV-2 nucleic acid amplification tests (NAATs) have been rapidly developed and quickly applied to clinical testing of COVID-19. Aim of this study was to evaluate the performance of four NAAT assays. METHODS: Limit of detection (LOD), precision, accuracy, analytical specificity and analytical interference studies on four NAATs (Daan, Sansure, Hybribio, and Bioperfectus) were performed according to Clinical Laboratory Standards Institute protocols and guidelines. The four NAATs were compared using 46 clinical samples. RESULTS: The LOD of the N gene for Daan, Sansure, and Hybribio was 500 copies/mL, and that for Bioperfectus was 1,000 copies/mL. The LOD of the ORF1ab gene for Daan, Bioperfectus, and Hybribio was 3,000 copies/mL, and that for Sansure was 2,000 copies/mL. A good precision was shown at the concentration above 20% of the LOD for all four NAATs, with all individual coefficients of variation below 3.6%. Satisfactory results were also observed in the accuracy, analytical specificity, and analytical interference tests. The results of the comparison test showed that Daan, Sansure, and Hybribio NAATs could detect the samples with a specificity of 100% (30/30) and a sensitivity of 100% (16/16), whereas Bioperfectus NAAT detected the samples with a specificity of 100% (30/30) and a sensitivity of 81.25% (13/16). However, no significant difference in sensitivity was found between Bioperfectus NAAT and the three other NAATs (p > 0.05). CONCLUSIONS: The four SARS-CoV-2 NAATs showed comparable performance, with the LOD of the N gene lower than the LOD of the ORF1ab gene.

Deafness Gene Mutations in Newborns in the Foshan Area of South China With Bloodspot-Based Genetic Screening Tests.

Purpose The aim of this study was to determine the rate of deafness gene mutations in the Foshan area of South China. Method We enrolled the infants delivered in Foshan Maternity and Children's Healthcare Hospital. Deafness gene mutation was detected by HibriMax method. Our study tested 47,538 newborns within 3 days after birth, including 13 sites in four genes: GJB2 (c.35 del G, c.176 del 16, c.235 del C, c.299 del AT, c.155 del TCTG), GJB3 (c.583 C>T), SLC26A4 (c.2168 A>G, c.919-2 A>G, c.1299 C>T), and mtDNA 12S rRNA (m.1555 A>G, m.1494 C>T, m.12201 T>C, m.7445 A>G). The birth condition of infants was collected, including sex, low or high birth weight, twins, and premature delivery. Results In a total of 47,538 newborns, 1,415 were positively identified with deafness gene mutations. The total rate of the deafness gene mutation was 2.976%. The carrier rates of GJB2 (c.35 del G, c.176 del 16, c.235 del C, c.299 del AT, c.155 del TCTG), GJB3 (c.583 C>T), SLC26A4 (c.2168 A>G, c.919-2 A>G, c.1299 C>T), and mtDNA 12S rRNA (m.1555 A>G, m.1494 C>T, m.12201 T>C, m.7445 A>G) mutations were 0.000%, 0.048%, 1.422%, 0.185%, 0.000%, 0.076%, 0.116%, 0.755%, 0.160%, 0.187%, 0.021%, 0.000%, and 0.006%, respectively. Conclusions Our study showed that the c.235 del C GJB2 mutation was the leading deafness-related mutation in the Foshan area of South China. Deafness gene mutations screening in newborns detected by bloodspot-based genetic screening tests can help the diagnosis of newborn congenital hearing loss.

Laparoscopic Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy for Type 2 Diabetes Mellitus in Nonseverely Obese Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Recently, randomized controlled trials (RCTs) have indicated that bariatric surgery in nonseverely obese patients with a body mass index (BMI) less than 35 kg/m2 might be even superior to medical therapy with regard to type 2 diabetes mellitus (T2DM) remission, but the efficacy of laparoscopic Roux-en-Y gastric bypass (LRYGB) compared with laparoscopic sleeve gastrectomy (LSG) in nonseverely obese patients has not been conclusively determined. The objective of this study is to compare LRYGB versus LSG for T2DM in nonseverely obese patients. METHODS: A meta-analysis identifying RCTs evaluating LRYGB versus LSG for T2DM in nonseverely obese patients was conducted. The primary outcome was T2DM remission. Additional analyses comprised percent excess weight loss (%EWL), BMI, waist circumference, hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), serum lipid level, medication use, quality of life, and adverse events. RESULTS: Four RCTs concerning total 296 patients were included. T2DM remission rate and %EWL were of no difference between the two bariatric procedures. LRYGB was associated with lower BMI, waist circumference, low-density lipoprotein, and higher high-density lipoprotein than LSG. However, HbA1c, FPG, total cholesterol, and triglyceride were not significantly different between the two surgical groups. The medication use and quality of life were improved in both two groups. The gastroesophageal reflux diseases of LRYGB group were less than that of LSG group. Dumping syndromes were noted more frequently in the LRYGB group. CONCLUSIONS: Both LRYGB and LSG have comparative effect on resolving T2DM in nonseverely obese patients at midterm follow-up. Further RCTs should address the potential risks and long-term effects of LRYGB and LSG in nonseverely obese patients.

Roux-en-Y Gastric Bypass Improves Metabolic Conditions in Association with Increased Serum Bile Acids Level and Hepatic Farnesoid X Receptor Expression in a T2DM Rat Model.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is an effective surgical treatment for type 2 diabetes mellitus (T2DM). The present study aimed to investigate the effects of RYGB on glucose homeostasis, lipid metabolism, and liver morphological adaption, as well as the changes in bile acids signaling and expression of its target regulatory factors involved in gluconeogenesis, lipogenesis, and fatty acid ß oxidation. METHODS: Twenty adult male T2DM rats induced by high-fat diet and a low dose of streptozotocin were randomly divided into sham and RYGB groups. The parameters of body weight, food intake, glucose tolerance, insulin sensitivity, serum lipid profiles, and bile acids level were assessed to evaluate metabolic changes. Liver sections were stained with hematoxylin-eosin (H&E) and oil red O to assess lipid accumulation. The mRNA and protein expression levels of farnesoid X receptor (FXR), small heterodimer partner (SHP), key regulatory factors of gluconeogenesis, lipogenesis, and fatty acid ß oxidation (phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-α (PPAR-α)) were determined through RT-PCR and Western blotting, respectively. RESULTS: RYGB induced significant improvements in glucose tolerance and insulin sensitivity, along with weight loss and decreased food intake. RYGB also decreased serum TG, FFAs, and increased bile acids levels. The lipid droplets in the liver were significantly decreased after RYGB. The RYGB group exhibited downregulated mRNA and protein expression levels of PEPCK, G6Pase, and SREBP-1c and upregulated expression of FXR, SHP, and PPAR-α in the liver. CONCLUSIONS: RYGB ameliorates glucose and lipid metabolism accompanied by weight loss and calorie restriction. The liver exhibited a marked improvement in lipid accumulation after RYGB. The bile acids level, FXR, and its target transcriptional factor SHP expression were elevated. Meanwhile, our study demonstrated that the increased bile acids-FXR signaling, followed by the reduced hepatic gluconeogenesis, lipogenesis, and increased fatty acid ß oxidation may contribute to improved metabolic conditions after RYGB.

The Consistency Research of Two Incubation Methods in Anti-EBNA1-IgA Antibody Detection.

BACKGROUND: The aim of this study was to prove the difference between 37°C water incubation method and the BEP III automated immunoassay analyzer incubation method in anti-EBNA1-IgA antibody detection and to find the best way to improve the consistency of the two incubation methods. METHODS: The 37°C water incubation method and BEP III analyzer incubation method were used with the same panel of samples (n = 39) in anti-EBNA1-IgA antibody detection. Except for incubation, the rest of the steps were performed by the BEP III analyzer in both groups. All the data were analyzed by SPSS 17.0 software. Line charts and bar charts were used to compare the difference between the two incubation methods in anti-EBNA1-IgA antibody detection. We planned to find the best incubation scheme for BEP III analyzer, consistent with the water incubation method, using three groups of prolonged incubation time experiments. RESULTS: A sample panel of 39 outpatients were analyzed by two incubation methods. The results showed by line charts that the water incubation method had higher S/CO values than the BEP III analyzer incubation method. Meanwhile the water incubation group had more positive results (61.5%) and less borderline positive results (35.9%) than that of the BEP III analyzer incubation group which were 43.5% and 51.2%, respectively, in the stacked bar charts. We found that by prolonging the incubation time in the BEP III analyzer for 6 minutes in the first and second incubation steps the S/CO values we increased and achieved statistically coincident results with water incubation group. CONCLUSIONS: There were biases between the 37°C water incubation method and the BEP III analyzer incubation method in anti-EBNA1-IgA antibody detection. The water incubation method had higher S/CO values than the BEP III analyzer incubation method in paired groups and led partly to a difference in test results. By prolonging the BEP III analyzer incubation time properly, it can reduce the difference to some extent resulting in statistically similar results with the water incubation method.

Long Noncoding RNA HOXC-AS1 Suppresses Ox-LDL-Induced Cholesterol Accumulation Through Promoting HOXC6 Expression in THP-1 Macrophages.

Atherosclerosis is a common pathological basis of cardiovascular disease, which remains the leading cause of mortality. Long noncoding RNAs (lncRNAs) are newly studied non-protein-coding RNAs involved in gene regulation, but how lncRNAs exert regulatory effect on atherosclerosis remains unclear. In this study, we found that lncRNA HOXC cluster antisense RNA 1 (HOXC-AS1) and homeobox C6 (HOXC6) were downregulated in carotid atherosclerosis by performing microarray analysis. The results were verified in atherosclerotic plaques and normal arterial intima tissues by quantitative reverse transcription PCR and western blot analysis. Lentivirus-mediated overexpression of HOXC-AS1 induced HOXC6 expression at mRNA and protein levels in THP-1 macrophages. Besides, oxidized low-density lipoprotein (Ox-LDL) decreased expression of HOXC-AS1 and HOXC6 in a time-dependent manner. Induction of cholesterol accumulation by Ox-LDL could be partly suppressed by overexpression of HOXC-AS1.

VNN1 promotes atherosclerosis progression in apoE-/- mice fed a high-fat/high-cholesterol diet.

Accumulated evidence shows that vanin-1 (VNN1) plays a key part in glucose metabolism. We explored the effect of VNN1 on cholesterol metabolism, inflammation, apoptosis in vitro, and progression of atherosclerotic plaques in apoE(-/-) mice. Oxidized LDL (Ox-LDL) significantly induced VNN1 expression through an ERK1/2/cyclooxygenase-2/PPARα signaling pathway. VNN1 significantly increased cellular cholesterol content and decreased apoAI and HDL-cholesterol (HDL-C)-mediated efflux by 25.16% and 23.13%, respectively, in THP-1 macrophage-derived foam cells (P < 0.05). In addition, VNN1 attenuated Ox-LDL-induced apoptosis through upregulation of expression of p53 by 59.15% and downregulation of expression of B-cell lymphoma-2 127.13% in THP-1 macrophage (P < 0.05). In vivo, apoE(-/-) mice were divided randomly into two groups and transduced with lentivirus (LV)-Mock or LV-VNN1 for 12 weeks. VNN1-treated mice showed increased liver lipid content and plasma levels of TG (124.48%), LDL-cholesterol (119.64%), TNF-α (148.74%), interleukin (IL)-1ß (131.81%), and IL-6 (156.51%), whereas plasma levels of HDL-C (25.75%) were decreased significantly (P < 0.05). Consistent with these data, development of atherosclerotic lesions was increased significantly upon infection of apoE(-/-) mice with LV-VNN1. These observations suggest that VNN1 may be a promising therapeutic candidate against atherosclerosis.

Dihydrocapsaicin suppresses proinflammatory cytokines expression by enhancing nuclear factor IA in a NF-κB-dependent manner.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease and represents the leading cause of morbidity and mortality throughout the world. Accumulating evidences have showed that Dihydrocapsaicin (DHC) has been found to exert multiple pharmacological and physiological effects. Nevertheless, the effects and possible mechanism of DHC on proinflammatory response remain largely unexplained. METHODS AND RESULTS: We found that DHC markedly upregulated NFIA and suppressed NF-κB expression in THP-1 macrophages. Up-regulation of proinflammatory cytokines induced by LPS including TNF-α, IL-1ß and IL-6 were markedly suppressed by DHC treatment. We also observed that protein level of NFIA was significantly increased while NF-κB and proinflammatory cytokines were decreased by DHC treatment in apoE(-/-) mice. Lentivirus-mediated overexpression of NFIA suppressed NF-κB and proinflammatory cytokines expression both in THP-1 macrophages and plaque tissues of apoE-/- mice. Moreover, treatment with lentivirus-mediated overexpression of NFIA made the down-regulation of DHC on NF-κB and proinflammatory cytokines expression notably accentuated in THP-1 macrophages and apoE(-/-) mice. In addition, treatment with siRNA targeting NF-κB accentuated the suppression of proinflammatory cytokines by lentivirus-mediated overexpression of NFIA. CONCLUSION: These observations demonstrated that DHC can significantly decrease proinflammatory cytokines through enhancing NFIA and inhibiting NF-κB expression and thus DHC may be a promising candidate as an anti-inflammatory drug for atherosclerosis as well as other disorders.

Roux-en-Y Gastric Bypass Surgery Suppresses Hepatic Gluconeogenesis and Increases Intestinal Gluconeogenesis in a T2DM Rat Model.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is an effective surgical treatment for type 2 diabetes mellitus (T2DM). The present study aimed to investigate the effects of RYGB on glucose homeostasis, lipid metabolism, and intestinal morphological adaption, as well as hepatic and intestinal gluconeogenesis. METHODS: Twenty adult male T2DM rats induced by high-fat diet and low dose of streptozotocin were randomly divided into sham and RYGB groups. The parameters of body weight, food intake, glucose tolerance, insulin sensitivity, and serum lipid profiles were assessed to evaluate metabolic changes. Intestinal sections were stained with hematoxylin and eosin (H&E) for light microscopy examination. The messenger RNA (mRNA) and protein expression levels of key regulatory enzymes of gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase)] were determined through reverse-transcription PCR (RT-PCR) and Western blotting, respectively. RESULTS: RYGB induced significant improvements in glucose tolerance and insulin sensitivity, along with weight loss and decreased food intake. RYGB also decreased serum triglyceride (TG) and free fatty acid (FFA) levels. The jejunum and ileum exhibited a marked increase in the length and number of intestinal villi after RYGB. The RYGB group exhibited downregulated mRNA and protein expression levels of PEPCK and G6Pase in the liver and upregulated expression of these enzymes in the jejunum and ileum tissues. CONCLUSIONS: RYGB ameliorates glucose and lipid metabolism accompanied by weight loss and calorie restriction. The small intestine shows hyperplasia and hypertrophy after RYGB. Meanwhile, our study demonstrated that the reduced hepatic gluconeogenesis and increased intestinal gluconeogenesis may contribute to improved glucose homeostasis after RYGB.