DNA Aptamer Raised against Advanced Glycation End Products Improves Sperm Concentration, Motility, and Viability by Suppressing Receptors for Advanced Glycation End Product-Induced Oxidative Stress and Inflammation in the Testes of Diabetic Mice.

Type 2 diabetes mellitus (T2DM) is a risk factor for male infertility, but the underlying molecular mechanisms remain unclear. Advanced glycation end products (AGEs) are pathogenic molecules for diabetic vascular complications. Here, we investigated the effects of the DNA aptamer raised against AGEs (AGE-Apt) on testicular and sperm abnormalities in a T2DM mouse model. KK-Ay (DM) and wild-type (non-DM) 4- and 7-week-old male mice were sacrificed to collect the testes and spermatozoa for immunofluorescence, RT-PCR, and histological analyses. DM and non-DM 7-week-old mice were subcutaneously infused with the AGE-Apt or control-aptamer for 6 weeks and were then sacrificed. Plasma glucose, testicular AGEs, and Rage gene expression in 4-week-old DM mice and plasma glucose, testicular AGEs, oxidative stress, and pro-inflammatory gene expressions in 7-week-old DM mice were higher than those in age-matched non-DM mice, the latter of which was associated with seminiferous tubular dilation. AGE-Apt did not affect glycemic parameters, but it inhibited seminiferous tubular dilation, reduced the number of testicular macrophages and apoptotic cells, and restored the decrease in sperm concentration, motility, and viability of 13-week-old DM mice. Our findings suggest that AGEs-Apt may improve sperm abnormality by suppressing AGE-RAGE-induced oxidative stress and inflammation in the testes of DM mice.

Glucagon secretion and its association with glycaemic control and ketogenesis during sodium-glucose cotransporter 2 inhibition by ipragliflozin in people with type 1 diabetes: Results from the multicentre, open-label, prospective study.

AIM: Clinical trials showed the efficacy of sodium-glucose cotransporter 2 inhibitors for type 1 diabetes (T1D) by significant reductions in body weight and glycaemic variability, but elevated susceptibility to ketoacidosis via elevated glucagon secretion was a potential concern. The Suglat-AID evaluated glucagon responses and its associations with glycaemic control and ketogenesis before and after T1D treatment with the sodium-glucose cotransporter 2 inhibitor, ipragliflozin. METHODS: Adults with T1D (n = 25) took 50-mg open-labelled ipragliflozin daily as adjunctive to insulin. Laboratory/clinical data including continuous glucose monitoring were collected until 12 weeks after the ipragliflozin initiation. The participants underwent a mixed-meal tolerance test (MMTT) twice [before (first MMTT) and 12 weeks after ipragliflozin treatment (second MMTT)] to evaluate responses of glucose, C-peptide, glucagon and ß-hydroxybutyrate. RESULTS: The area under the curve from fasting (0 min) to 120 min (AUC0-120min) of glucagon in second MMTT were significantly increased by 14% versus first MMTT. The fasting and postprandial ß-hydroxybutyrate levels were significantly elevated in second MMTT versus first MMTT. The positive correlation between postprandial glucagon secretion and glucose excursions observed in first MMTT disappeared in second MMTT, but a negative correlation between fasting glucagon and time below range (glucose, <3.9 mmol/L) appeared in second MMTT. The percentage changes in glucagon levels (fasting and AUC0-120min) from baseline to 12 weeks were significantly correlated with those in ß-hydroxybutyrate levels. CONCLUSIONS: Ipragliflozin treatment for T1D increased postprandial glucagon secretion, which did not exacerbate postprandial hyperglycaemia but might protect against hypoglycaemia, leading to reduced glycaemic variability. The increased glucagon secretion might accelerate ketogenesis when adequate insulin is not supplied.

Novel endoscopic duodenal observation protocol based on Seven Pictures Rule for detecting duodenal neoplasms during esophagogastroduodenoscopy: Prospective observational study.

OBJECTIVES: No protocol for esophagogastroduodenoscopic examination of the duodenum has been established. We examined the feasibility and ability to detect neoplasms of a novel duodenal examination protocol. METHODS: This was a two-facility, prospective, observational study. Our protocol, the Seven Pictures Rule (7PR), requires pictures of the following seven locations: anterior and posterior to the bulb, area of and contralateral to the superior duodenal angle, area of and contralateral to the ampulla, and the transverse duodenum. The primary outcome was rate of completion of 7PR. Secondary outcomes were overall rates of detecting neoplasms, rates of detecting neoplasms for each location, examination time, and completion rates for standard or ultrathin endoscopes. RESULTS: There were 1549 participants. The 7PR completion rate was 81.1% and the detection rates of overall neoplasms, adenomas, and carcinomas were 0.84%, 0.71%, and 0.06%, respectively. The area in which most neoplasms was detected was contralateral to the ampulla (69.2%), and the fewest the transverse duodenum (0%). Mean duration of duodenal examination was 53.1 s. Completion rates for standard vs. ultrathin were 84.4% (1077/1276) vs. 65.6% (179/273) (P < 0.01), respectively. CONCLUSIONS: Seven Pictures Rule is acceptable for duodenal examination and a potential quality indicator.

Subcutaneous Infusion of DNA-Aptamer Raised against Advanced Glycation End Products Prevents Loss of Skeletal Muscle Mass and Strength in Accelerated-Aging Mice.

We have developed DNA aptamers that can inhibit the toxic effects of advanced glycation end products (AGE-Apts). We herein evaluated the effects of AGE-Apts on muscle mass and strength in senescence-accelerated mouse prone 8 (SAMP8) mice. Eight-month-old male SAMP8 mice received subcutaneous infusion of control DNA aptamers (CTR-Apts) or AGE-Apts. Mice in an age-matched senescence-accelerated mouse resistant strain 1 (SAMR1) group were treated with CTR-Apts as controls. The soleus muscles were collected after the 8-week intervention for weight measurement and histological, RT-PCR, and immunofluorescence analyses. Grip strength was measured before and after the 8-week intervention. AGE-Apt treatment inhibited the progressive decrease in the grip strength of SAMP8 mice. SAMP8 mice had lower soleus muscle weight and fiber size than SAMR1 mice, which was partly restored by AGE-Apt treatment. Furthermore, AGE-Apt-treated SAMP8 mice had a lower interstitial fibrosis area of the soleus muscle than CTR-Apt-treated SAMP8 mice. The soleus muscle levels of AGEs, oxidative stress, receptor for AGEs, and muscle ring-finger protein-1 were increased in the CTR-Apt-treated mice, all of which, except for AGEs, were inhibited by AGE-Apt treatment. Our present findings suggest that the subcutaneous delivery of AGE-Apts may be a novel therapeutic strategy for aging-related decrease in skeletal muscle mass and strength.

Role of Mir-452-5p Overexpression in Epithelial-Mesenchymal Transition (EMT) in Early-stage Colorectal Cancer.

BACKGROUND/AIM: The microRNA miR-452-5p holds a critical role in the progression of multiple tumor formations, but there is limited understanding regarding the epithelial-mesenchymal transition (EMT) progression and its underlying mechanisms in the early-stage colorectal cancer (CRC). We aimed to explore the change in miRNA expression in early-stage CRC and examine the role of these miRNAs in CRC. MATERIALS AND METHODS: The expression levels of miR-452-5p in tissues and cells of early-stage CRC were determined by real-time quantitative polymerase chain reaction. Additionally, the biological effects of miR-452-5p on CRC were investigated by in vitro functional experiments. RESULTS: The expression levels of miR-452-5p were found increased in early-stage CRC tissue. We found that miR-452-5p promoted CRC cell proliferation but inhibited epithelial-mesenchymal transition. Furthermore, miR-452-5p promoted cell proliferation through activation of the extracellular signal-regulated kinase pathway, and inhibited cell invasion through suppression of Slug (Snail2) expression and up-regulation of E-cadherin expression. CONCLUSION: The expression of miR-452-5p is up-regulated in early CRC and suppresses epithelial-mesenchymal transition in CRC. These discoveries suggest that miR-452-5p has the potential to serve as a viable therapeutic target for CRC.

Effective and Secure Closure after Duodenal Endoscopic Submucosal Dissection: Combination of Endoscopic Ligation with O-Ring Closure and Over-the-Scope Clip.

Duodenal endoscopic submucosal dissection (ESD) is associated with high incidences of intraoperative complications and delayed adverse events (AEs). Delayed AEs can be reduced by closing the post-ESD defects. We developed a new method of closure after duodenal ESD, combining endoscopic ligation with O-ring closure (E-LOC) with an over-the-scope clip (OTSC) (Band OTSC; B-OTSC). Here, we conducted a single-center, retrospective, observational study to investigate the efficacy and safety of the B-OTSC method for preventing delayed AEs in patients undergoing duodenal ESD. The study included nine patients with superficial nonpapillary duodenal epithelial tumors who underwent ESD and were closed with B-OTSC from February 2021 to February 2023. There were no delayed AEs (0%), the mean (± standard deviation) closure time was 53 ± 21.6 min, the complete closure rate was 100%, and the mean hospital stay was 7.8 ± 1.8 days. The sustained closure rates at postoperative days 3 and 7 were 88.9% and 88.9%, respectively. The historical analysis indicated a significant difference in cost between B-OTSC and conventional OTSC (p < 0.01). In conclusion, B-OTSC was a safe, secure, and cost-effective method of closure after duodenal ESD, even in patients with post-ESD defects of more than half the circumference.

SMTP-44D Inhibits Atherosclerotic Plaque Formation in Apolipoprotein-E Null Mice Partly by Suppressing the AGEs-RAGE Axis.

SMTP-44D has been reported to have anti-oxidative and anti-inflammatory reactions, including reduced expression of receptor for advanced glycation end products (RAGE) in experimental diabetic neuropathy. Although activation of RAGE with its ligands, and advanced glycation end products (AGEs), play a crucial role in atherosclerotic cardiovascular disease, a leading cause of death in diabetic patients, it remains unclear whether SMTP-44D could inhibit experimental atherosclerosis by suppressing the AGEs-RAGE axis. In this study, we investigated the effects of SMTP-44D on atherosclerotic plaque formation and expression of AGEs in apolipoprotein-E null (Apoe-/-) mice. We further studied here whether and how SMTP-44D inhibited foam cell formation of macrophages isolated from Apoe-/- mice ex vivo. Although administration of SMTP-44D to Apoe-/- mice did not affect clinical or biochemical parameters, it significantly decreased the surface area of atherosclerotic lesions and reduced the atheromatous plaque size, macrophage infiltration, and AGEs accumulation in the aortic roots. SMTP-44D bound to immobilized RAGE and subsequently attenuated the interaction of AGEs with RAGE in vitro. Furthermore, foam cell formation evaluated by Dil-oxidized low-density lipoprotein (ox-LDL) uptake, and gene expression of RAGE, cyclin-dependent kinase 5 (Cdk5) and CD36 in macrophages isolated from SMTP-44D-treated Apoe-/- mice were significantly decreased compared with those from saline-treated mice. Gene expression levels of RAGE and Cdk5 were highly correlated with each other, the latter of which was also positively associated with that of CD36. The present study suggests that SMTP-44D may inhibit atherosclerotic plaque formation in Apoe-/- mice partly by blocking the AGEs-RAGE-induced ox-LDL uptake into macrophages via the suppression of Cdk5-CD36 pathway.

Does an Extraoral Suction Device Reduce Aerosol Generation and Prevent Droplet Exposure to the Examiner during Esophagogastroduodenoscopy?

Esophagogastroduodenoscopy (EGD) is an aerosol-generating procedure. A major challenge in the COVID-19 era is how to prevent the spread of aerosols and droplets in endoscopic units. We evaluated the effectiveness of an extraoral suction device in preventing indoor aerosol diffusion and droplet exposure for examiners. The study involved 61 patients who underwent EGD at our institution from 1 February to 31 March 2022. To determine whether aerosol spread increases before or after EGD examination with an extraoral suction device located in front of the patient's mouth, aerosols of 0.3, 0.5, 1, 3, 5, and 10 µm were measured with a handheld particle counter. The degree of contamination of the plastic gowns on the examiners was assessed using the rapid adenosine triphosphate test. The extraoral suction device significantly reduced the diffusion of large particles (3, 5, and 10 µm) after finishing the EGD examination. However, the diffusion of small particles (0.3 and 0.5 µm) was significantly increased. This extraoral suction device was effective in reducing large particle diffusion during EGD examination but was limited for minimizing small particle diffusion or droplet exposure to the examiner.

Comparison of endoscopic closure versus non-closure for post-gastric endoscopic submucosal dissection artificial floor in antithrombotic therapy: a propensity score-matched analysis.

Background: The management of delayed bleeding after gastric endoscopic submucosal dissection (ESD) is currently an important issue because of recent increases in the number of patients on antithrombotic therapy. Artificial ulcer closure has been shown to prevent delayed complications in the duodenum and colon. However, its effectiveness in cases involving the stomach remains unclear. In this study, we aimed to determine whether endoscopic closure reduces post-ESD bleeding in patients undergoing antithrombotic therapy. Methods: We retrospectively analyzed 114 patients who had undergone gastric ESD while on antithrombotic therapy. The patients were allocated to one of 2 groups: a closure group (n=44) and a non-closure group (n=70). Endoscopic closure had been performed using multiple hemoclips or using the endoscopic ligation with O-ring closure method after coagulation of exposed vessels on the artificial floor. Propensity score matching resulted in 32 pairs of patients (closure vs. non-closure 32:32). The primary outcome was post-ESD bleeding. Results: The post-ESD bleeding rate was significantly lower in the closure group (0%) than in the non-closure group (15.6%) (P=0.0264). There were no significant differences between the 2 groups regarding white blood cell count, C-reactive protein, maximum body temperature, or scores on a verbal rating scale that assesses the degree of abdominal pain. Conclusion: Endoscopic closure may contribute to decreasing the incidence of post-ESD gastric bleeding in patients undergoing antithrombotic therapy.

Comparison of Needle Knife versus Scissors Forceps for Colorectal Endoscopic Submucosal Dissection: A Prospective Randomized Study.

BACKGROUND AND AIM: To evaluate the efficacy and safety of a grasping-type knife, called Clutch Cutter (CC), for colorectal endoscopic submucosal dissection (C-ESD). METHODS: This was a randomized prospective study. Patients who underwent C-ESD for colorectal neoplasms >20 mm and <50 mm in size were enrolled, dividing into two groups: ESD using needle type of dual knife alone (D-group) and circumferential incision using dual knife followed by submucosal dissection using CC (CC-group). The primary outcome was the self-completion rate. The secondary outcomes were intraoperative complication rate, procedure time, and en bloc resection rate. RESULTS: A total of 45 patients were allocated to the D-group and 43 to the CC-group were allocated. The self-completion rate was higher in the CC-group (87% [39/45] vs. 98% [42/43]). All of the six patients with an incomplete procedure in the D-group were completely resected with CC use. The intraoperative complication rate was not significant in either group (D vs. CC: 2% vs. 0%). The mean procedure time was significantly shorter in the D-group than that in the CC-group (62.0 vs. 81.1 min; p = 0.0036). The en bloc resection rate was 100% in the D-group and 98% in the CC-group. CONCLUSIONS: While dual knife use is superior to CC in terms of time efficiency, the use of CC may be a safe and efficacious option for achieving complete C-ESD.

Effects of olmesartan and amlodipine on blood pressure, endothelial function, and vascular inflammation.

BACKGROUND: Anti-hypertensive drugs can improve vascular endothelial function. However, the mechanism remains to be elucidated. OBJECTIVES: This study sought to investigate mechanisms of anti-hypertensive drugs on improvement of vascular endothelial function in patients with essential hypertension. METHODS: Forty-five patients (mean age 58.5 ± 11.2 years) with uncontrolled essential hypertension were randomly assigned to receive olmesartan, an angiotensin II type 1 receptor blocker (ARB) (N = 23), or amlodipine, a calcium channel blocker (CCB) (N = 22), for 6 months. Endothelial function was evaluated by flow-mediated dilatation (FMD) of the brachial artery. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR) within the carotid arteries using 18F-fluorodeoxyglucose-positron emission tomography combined with computed tomography. RESULTS: There were no significant differences of baseline clinical data between the ARB and CCB groups. Both anti-hypertensive drugs comparably lowered blood pressure and increased %FMD. TBR values were reduced by olmesartan (P < .001), while blood pressure variability was decreased by amlodipine (P = .004). Changes in %FMD from baseline (Δ%FMD) were inversely associated with ΔTBR in the olmesartan group (r = - .606, P = .003) and with Δsystolic blood pressure variability in the amlodipine group (r = - .434, P = .039). CONCLUSION: Our study indicated that olmesartan and amlodipine could improve endothelial function in patients with essential hypertension in different manners, suppression of vascular inflammation, and decrease in blood pressure variability, respectively.

Does Deep Learning Enhance the Estimation for Spatially Explicit Built Environment Stocks through Nighttime Light Data Set? Evidence from Japanese Metropolitans.

Built environment stocks have attracted much attention in recent decades because of their role in material and energy flows and environmental impacts. Spatially refined estimation of built environment stocks benefits city management, for example, in urban mining and resource circularity strategy making. Nighttime light (NTL) data sets are widely used and are regarded as high-resolution products in large-scale building stock research. However, some of their limitations, especially blooming/saturation effects, have hampered performance in estimating building stocks. In this study, we experimentally proposed and trained a convolution neural network (CNN)-based building stock estimation (CBuiSE) model and applied it to major Japanese metropolitan areas to estimate building stocks using NTL data. The results show that the CBuiSE model is capable of estimating building stocks at a relatively high resolution (approximately 830 m) and reflecting spatial distribution patterns, although the accuracy needs to be further improved to enhance the model performance. In addition, the CBuiSE model can effectively mitigate the overestimation of building stocks arising from the blooming effect of NTL. This study highlights the potential of NTL to provide a new research direction and serve as a cornerstone for future anthropogenic stock studies in the fields of sustainability and industrial ecology.

Endoscopic Ligation with O-Ring Closure for Mucosal Defects after Rectal Endoscopic Submucosal Dissection: A Feasibility Study (with Video).

INTRODUCTION: Mucosal defect closure after colorectal endoscopic submucosal dissection (ESD) may prevent post-ESD adverse events. Delayed bleeding is a particular concern in the rectum due to the presence of numerous blood vessels. However, rectal defect closure often fails due to the thick rectal wall. This study aimed to examine the feasibility of our newly developed endoscopic ligation with O-ring closure (E-LOC) for defects after rectal ESD. METHODS: This was a prospective observational study conducted at a single institution. After excluding 2 patients with tumors mostly extending into the anal canal, the study cohort comprised 30 consecutive patients who underwent ESD of rectal neoplasms between July 2020 and July 2021. E-LOC using an endoscopic variceal ligation device was performed for closing mucosal defects after rectal ESD. The primary outcome was the complete closure rate. The secondary outcomes were the delayed bleeding rate, E-LOC procedure time, sustained closure rates on postoperative day (POD) 3, and E-LOC-associated complications. RESULTS: Complete closure of the defect (median defect size 29.0 mm) was successfully achieved in 24 cases (80%). Delayed bleeding occurred in one case with incomplete closure (3.3%). The median E-LOC procedure time was 25.5 min (interquartile range, 20.0-30.0 min). The sustained closure rates were 83.3% (20/24) on POD 3 in the 24 cases with complete closure. No E-LOC-associated complications occurred. DISCUSSION/CONCLUSIONS: E-LOC was feasible for defect closure after rectal ESD, and probably led to a decreased incidence of delayed bleeding.

Comparison of purse-string suture versus over-the-scope clip for gastric endoscopic full-thickness closure: traction and leak pressure testing in ex vivo porcine model.

BACKGROUND: The recently developed endoscopic full-thickness resection technique requires reliable closure. The main closure methods are the purse-string suture (PSS) technique and over-the-scope clip (OTSC) technique; however, basic data on the closure strength of each technique are lacking. This study was performed to compare the closure strengths of these two methods in an ex vivo porcine model. METHODS: In the traction test, a virtual 5-cm full-thickness closure line was closed by the following six methods three times each: conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture. The primary endpoint was the tension at the starting point of dehiscence, measured in Newtons (N) by an automatic traction machine. In the leak test, a 15-mm gastric full-thickness defect was closed by PSS or OTSC six times each, and the closed stomach was then pressurized in a water container. The primary endpoint was the leak pressure when air bubbles appeared. The secondary endpoints were the procedure time and presence of complete inverted closure. RESULTS: The mean tension was 2.16, 3.68, 5.15, 18.30, 19.30, and 62.40 N for conventional hemoclips, mucosal PSS, seromuscular PSS, mucosal OTSC, seromuscular OTSC, and surgical suture, respectively. Complete inverted closure was observed for seromuscular PSS, seromuscular OTSC, and surgical suture. The mean leak pressure was 13.7 and 24.8 mmHg in the PSS and OTSC group, respectively (P < 0.01). The mean procedure time was 541 and 169 s in the PSS and OTSC group, respectively (P < 0.01). Complete inverted closure was observed in OTSC alone. CONCLUSION: The OTSC, which allows complete inverted closure, showed greater closure strength than PSS. Considering the size limitation suitable for single OTSC, a therapeutic strategy for closing the larger size is further warranted.

Poor association between dihydropyrimidine dehydrogenase (DPYD) genotype and fluoropyrimidine-induced toxicity in an Asian population.

OBJECTIVE: Dihydropyrimidine dehydrogenase (DPYD) genotype is closely associated with fluoropyrimidine (FP)-induced toxicities in Caucasian population and European Medicines Agency now recommends DPYD genotype-based FP dosing strategy. PATIENTS AND METHODS: The current study aimed to investigate their impact on FP-related toxicities in an Asian population using genome-wide association study (GWAS) data set from 1364 patients with colon cancer. RESULTS: Among 82 variants registered in the Clinical Pharmacogenetics Implementation Consortium, 74 DPYD variants were directly genotyped in GWAS cohort; however, only 7 nonsynonymous DPYD variants (CPIC variants) were identified and none of the four recurrent DPYD variants (DPYD*2A, c.2846A>T, c.1679T>G, c.1236G>A) were included. Seven CPIC variants were investigated for their association with the incidence of FP-related toxicities; however, none of these variants revealed a significant correlation with FP-related toxicities. CONCLUSION: These data suggested that the DPYD genotype registered in CPIC plays a minor role in FP-related toxicities in an Asian population.

Computational Screening and Experimental Validation of Inhibitor Targeting the Complex Formation of Grb14 and Insulin Receptor.

The development of drugs targeting gene products associated with insulin resistance holds the potential to enhance our understanding of type 2 diabetes mellitus (T2DM). The virtual screening, based on a three-dimensional (3D) protein structure, is a potential technique to accelerate the development of molecular target drugs. Among the targets implicated in insulin resistance, the genetic characterization and protein function of Grb14 have been clarified without contradiction. The Grb14 gene displays significant variations in T2DM, and its gene product is known to inhibit the function of the insulin receptor (IR) by directly binding to the tyrosine kinase domain. In the present study, a virtual screening, based on a 3D structure of the IR tyrosine kinase domain (IRß) in complex with part of Grb14, was conducted to find compounds that can disrupt the complex formation between Grb14 and IRß. First, ten compounds were selected from 154,118 compounds via hierarchical in silico structure-based drug screening, composed of grid docking-based and genetic algorithm-based programs. The experimental validations suggested that the one compound can affect the blood glucose level. The molecular dynamics simulations and co-immunoprecipitation analysis showed that the compound did not completely suppress the protein-protein interaction between Grb14 and IR, though competitively bound to IR with the tyrosine kinase pseudosubstrate region in Grb14.

Acceptability of Hybrid Endoscopic Submucosal Dissection Using Multifunctional Snare for Small-sized Gastric Neoplasms: A Prospective Observational Study.

BACKGROUND AND AIMS: The most suitable procedure for resecting small-sized gastric neoplasms remains unclear. Endoscopic mucosal resection leads to non-curative resection owing to slippage of the snare, and technically difficult endoscopic submucosal dissection (ESD) is instrumentally uneconomical. A novel, cost-effective, multifunctional snare called SOUTEN is available as a hybrid ESD (h-ESD) device developed for facilitating ESD. This study aimed to assess the acceptability of h-ESD using the SOUTEN for resecting small-sized gastric neoplasms. METHODS: This was a prospective observational study conducted at our single institution between March 2019 and March 2021. Fifty-seven consecutive patients who underwent h-ESD using SOUTEN for small-sized gastric neoplasms ≤15 mm involving adenoma and tubular-type mucosal carcinoma without ulceration were enrolled. The primary outcome was curative resection rate for h-ESD. Secondary outcomes were the rates of conversion to ESD, rate of total (h-ESD + ESD) curative resection, procedure time, rates of intra-and post- operative complications, and presence of additional knives excluding hemostatic forceps. RESULTS: The curative resection rate of h-ESD was 89.5% (51/57). The total (h-ESD + ESD) curative resection rate was 94.7% (54/57). The mean procedure time was 21.2 (±16.5) minutes. One case of delayed bleeding occurred. Additional knives were applied in two cases. CONCLUSIONS: The cost-efficient h-ESD using SOUTEN can be an acceptable procedure for resecting small- sized gastric neoplasms.

Predictive ability of serum advanced glycation end products at 11 to 13 weeks of gestation for early-onset preeclampsia.

BACKGROUND: Placental hypoxia and resultant oxidative stress have been associated with the development of preeclampsia. Oxidative stress promotes the formation of advanced glycation end products. OBJECTIVE: This study aimed to assess whether serum levels of advanced glycation end products during the early stage of pregnancy are a predictive biomarker of early-onset and late-onset preeclampsia. STUDY DESIGN: This was a nested case-control study that included 6 women with early-onset preeclampsia, 21 women with late-onset preeclampsia, and 50 age- and body mass index-matched healthy female control subjects. All women enrolled in the study had a complete medical history, including mean arterial pressure and uterine artery pulsatility index measurements. Furthermore, the women underwent blood chemistry analysis, including circulating levels of advanced glycation end products, soluble fms-like tyrosine kinase-1, and placental growth factor. Clinical measurements and biochemistry were evaluated at 11 to 13 and 19 to 24 weeks of gestation. RESULTS: The median serum concentrations of advanced glycation end products at 11 to 13 weeks of gestation were significantly higher in patients with early-onset preeclampsia than in those with late-onset preeclampsia and control subjects (6.62 vs 4.10 vs 3.77; P<.05), but no significant difference was found in advanced glycation end products at 19 to 24 weeks of gestation among the 3 groups. The advanced glycation end product-to-placental growth factor ratio in the first trimester of pregnancy was significantly higher in patients with early-onset preeclampsia than in those with late-onset preeclampsia or control subjects (0.78 vs 0.10 vs 0.10; P<.05). The area under the receiver operating characteristic curve values for patients with early-onset preeclampsia were 0.782 (95% confidence interval, 0.522-0.922), 0.855 (95% confidence interval, 0.433-0.978), and 0.925 (95% confidence interval, 0.724-0.983) for the advanced glycation end product and placental growth factor levels and advanced glycation end product-to-placental growth factor ratios, respectively. This population achieved a 100% detection rate for predicting early-onset preeclampsia at a screen-positive rate of 10% by combining the advanced glycation end product-to-placental growth factor ratio and the mean arterial pressure. CONCLUSION: The study results suggested that an elevated advanced glycation end product-to-placental growth factor ratio and mean arterial pressure at 11 to 13 weeks of gestation could be a potential biomarker for predicting the future development of early-onset preeclampsia.