Sulfated polysaccharides and immune response: promoter or inhibitor?

Sulfated polysaccharides, which frequently connect to core protein, are expressed not only on cell surface but also throughout the extracellular matrix. Besides providing structural integrity of cells, sulfated polysaccharides interact with a variety of sulfated polysaccharides-binding proteins, such as growth factors, cytokines, chemokines and proteases. Sulfated polysaccharides play two-edged roles, inhibitor and promoter, in immune response. Some sulfated polysaccharides act as the immunosuppressor by blocking inflammatory signal transduction induced by proinflammatory cytokines, suppressing the activation of complement and inhibiting the process that leukocytes adhere to and pass through endothelium. On the contrary, the interaction between immune cells and sulfated polysaccharides produced by bacteria, endothelial cells and immune cells initiate the occurrence of immune response. It promotes the processes of recognizing and arresting antigen, migrating transendothelium, moving into and out of immune organ and enhancing the proliferation of lymphocyte. The structure of sulfated polysaccharides, such as molecular weight and sulfated sites heterogeneity, especially the degree of disaccharide sulfation, position of the sulfate moiety and organization of sulfated domains, may play critical role in their controversial effects. As a consequence, the interaction between sulfated polysaccharides and sulfated polysaccharide-binding proteins may be changed by modifying the structure of sulfated polysaccharides chains. The administration of drug targeting sulfated polysaccharide-protein interaction may be useful in treating inflammatory related diseases.     

Gastric Cancer Risk Was Associated with Dietary Factors Irritating the Stomach Wall: A Case–Control Study in Korea

The incidence of gastric cancer is high in Korea, and dietary factors are important risk factors for gastric cancer. This study examined whether gastric cancer risk was related to dietary factors that directly irritate the stomach wall. This case–control study consisted of 308 matched pairs of gastric cancer cases and controls recruited from 2002 to 2006 at two hospitals in Korea. Dietary assessments were completed using a food frequency questionnaire and a dietary habit questionnaire. Gastric cancer risk was increased for high meal frequency of >3 vs. low meal frequency of ≤3 times per day, overeating vs. not overeating, and preferred vs. not preferred spicy or salty foods. Furthermore, participants with dietary factors of high meal frequency, overeating, and preference for spicy or salty foods elevated the risk of gastric cancer compared to those with low meal frequency, not overeating, and not preferring spicy or salty foods, simultaneously. In conclusion, gastric cancer risk was significantly increased in people with dietary factors that irritate the stomach wall, such as high meal frequency, overeating, and preference for spicy or salty foods.     

Efficacy and Safety of Apatinib in Patients with Recurrent or Refractory Melanoma

BackgroundThe prognosis of patients with metastatic malignant melanoma is very poor and partly due to resistance to conventional chemotherapies. The study’s objectives were to assess the activity and tolerability of apatinib, an oral small molecule anti-angiogenesis inhibitor, in patients with recurrent advanced melanoma.MethodsThis was a single-arm, single-center phase II trial. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Eligible patients had received at least one first-line therapy for advanced melanoma and experienced recurrence. Apatinib (500 mg) was orally administered daily.ResultsFifteen patients (V660E BRAF status: 2 mutation, 2 unknown, 11 wild type) were included in the analysis. The median PFS was 4.0 months. There were two major objective responses, for a 13.3% response rate. Eleven patients had stable disease, with a DCR of 86.7%. The median OS was 12.0 months. The most common treatment-related adverse events of any grade were hypertension (80.0%), mucositis oral (33.3%), hand-foot skin reaction (26.7%), and liver function abnormalities, hemorrhage, diarrhea (each 20%). The only grade ≥3 treatment-related adverse effects that occurred in 2 patients was hypertension (6.7%) and mucositis (6.7%). No treatment-related deaths occurred.ConclusionApatinib showed antitumor activity as a second- or above-line therapy in patients with malignant melanoma. The toxicity was manageable.ClinicalTrials.gov Identifier{"type":"clinical-trial","attrs":{"text":"NCT03383237","term_id":"NCT03383237"}}NCT03383237     

基于SPSS的生物统计数据的2D3D作图

目的结合生物统计学的软件SPSS 11.0,进行数据处理和图形结果输出,并对SPSS 11.0图表输出方式加以改进,结合MATLAB进行模拟演示,以得到更加形象并具有动态趋势的统计图。方法结合NCPP和CPP对小鼠脾脏激活作用的比较的数据,对其进行独立样本t检验,然后利用MATLAB编程进行演示。结论实现SPSS 11.0软件与MATLAB编程的相互结合,得到很形象的图形结果。     

Catalyst-free reductive cyclization of bis(2-aminophenyl) disulfide with CO2 in the presence of BH3NH3 to synthesize 2-unsubstituted benzothiazole derivatives

An efficient and catalyst-free methodology for the reductive cyclization of various disulfides using BH₃NH₃ as a reductant and CO₂ as a C1 resource was developed. The desired 2-unsubstituted benzothiazole derivatives were obtained in good to excellent yields. Moreover, mechanism investigation demonstrated that BH₃NH₃ played an important role in the formation of benzothiazole. As a reducing agent, BH₃NH₃ reduced CO₂ and cleaved the S–S bond of the disulfide efficiently. In addition, the N–H bond of the amino group was also activated by BH₃NH₃. To the best of our knowledge, this is an unprecedented catalyst-free protocol for the synthesis of 2-unsubstituted benzothiazole from bis(2-aminophenyl) disulfide and CO₂.

An efficient and catalyst-free methodology for the reductive cyclization of various disulfides using BH₃NH₃ as a reductant and CO₂ as a C1 resource was developed.     

Effects of Chronic Exposure to Diets Containing Moldy Corn or Moldy Wheat Bran on Growth Performance,Ovarian Follicular Pool,and Oxidative Status of Gilts

Background: We investigated the effect of replacing normal corn (NC) or normal wheat bran (NW) with moldy corn (MC) or moldy wheat bran (MW) on growth, ovarian follicular reserves, and oxidative status. Methods: Sixty-three Landrace × Yorkshire gilts were assigned to seven diets formulated by using MC to replace 0% (control), 25% (25% MC), 50% (50% MC), 75% (75% MC), and 100% NC (100% MC), MW to replace 100% NW (100% MW), and MC and MW to replace 100% NC and 100% NW (100% MC + MW), from postnatal day 110 to day 19 of the second estrous cycle. Results: Feeding the gilts with MC or MW induced a lower average daily gain at days 29–56 of the experiment. Age at puberty remained unchanged, but MC inclusion resulted in a linear decrease in antral follicles with diameter >3.0 mm, and control gilts had a 12.7 more large antral follicles than gilts in the 100% MC + MW treatment. MC inclusion linearly decreased the numbers of primordial follicles, growing follicles, and corpora lutea, associated with a lower anti-Müllerian hormone level in serum and 17β-estradiol level in follicular fluid. MC inclusion decreased the serum concentrations of insulin-like growth factor 1 and its mRNA levels in the liver, combined with higher malondialdehyde concentration and lower total superoxide dismutase activities in serum and liver. Conclusion: Chronic exposure to MC-containing diets caused the loss of follicles, even if levels of deoxynivalenol, zearalenone, and aflatoxin B1 were below the levels allowed by China and Europe standards.     

Consumption of Dietary Fiber with Different Physicochemical Properties during Late Pregnancy Alters the Gut Microbiota and Relieves Constipation in Sow Model

Constipation is a common problem in sows and women during late pregnancy. Dietary fiber has potential in the regulation of intestinal microbiota, thereby promoting intestinal motility and reducing constipation. However, the effects of fibers with different physicochemical properties on intestinal microbe and constipation during late pregnancy have not been fully explored. In this study, a total of 80 sows were randomly allocated to control and one of three dietary fiber treatments from day 85 of gestation to delivery: LIG (lignocellulose), PRS (resistant starch), and KON (konjaku flour). Results showed that the defecation frequency and fecal consistency scores were highest in PRS. PRS and KON significantly increased the level of gut motility regulatory factors, 5-hydroxytryptamine (5-HT), motilin (MTL), and acetylcholinesterase (AChE) in serum. Moreover, PRS and KON promoted the IL-10 level and reduced the TNF-α level in serum. Furthermore, maternal PRS and KON supplementation significantly reduced the number of stillborn piglets. Microbial sequencing analysis showed that PRS and KON increased short-chain fatty acids (SCFAs)-producing genera Bacteroides and Parabacteroides and decreased the abundance of endotoxin-producing bacteria Desulfovibrio and Oscillibacter in feces. Moreover, the relative abundance of Turicibacter and the fecal butyrate concentration in PRS were the highest. Correlation analysis further revealed that the defecation frequency and serum 5-HT were positively correlated with Turicibacter and butyrate. In conclusion, PRS is the best fiber source for promoting gut motility, which was associated with increased levels of 5-HT under specific bacteria Turicibacter and butyrate stimulation, thereby relieving constipation. Our findings provide a reference for dietary fiber selection to improve intestinal motility in late pregnant mothers.     

Application of Machine Learning Approaches to Predict Postnatal Growth Failure in Very Low Birth Weight Infants

PurposeThe aims of the study were to develop and evaluate a machine learning model with which to predict postnatal growth failure (PGF) among very low birth weight (VLBW) infants.Materials and MethodsOf 10425 VLBW infants registered in the Korean Neonatal Network between 2013 and 2017, 7954 infants were included. PGF was defined as a decrease in Z score >1.28 at discharge, compared to that at birth. Six metrics [area under the receiver operating characteristic curve (AUROC), accuracy, precision, sensitivity, specificity, and F1 score] were obtained at five time points (at birth, 7 days, 14 days, 28 days after birth, and at discharge). Machine learning models were built using four different techniques [extreme gradient boosting (XGB), random forest, support vector machine, and convolutional neural network] to compare against the conventional multiple logistic regression (MLR) model.ResultsThe XGB algorithm showed the best performance with all six metrics across the board. When compared with MLR, XGB showed a significantly higher AUROC (p=0.03) for Day 7, which was the primary performance metric. Using optimal cut-off points, for Day 7, XGB still showed better performances in terms of AUROC (0.74), accuracy (0.68), and F1 score (0.67). AUROC values seemed to increase slightly from birth to 7 days after birth with significance, almost reaching a plateau after 7 days after birth.ConclusionWe have shown the possibility of predicting PGF through machine learning algorithms, especially XGB. Such models may help neonatologists in the early diagnosis of high-risk infants for PGF for early intervention.     

Initial Abdominal CT and Laboratory Findings Prior to Diagnosis of Crohn’s Disease in Children

PurposeTo identify initial abdominal computed tomography (CT) and laboratory findings prior to a diagnosis of Crohn’s disease (CD) in children.Materials and MethodsIn this retrospective study, patients (≤18 year-old) who were diagnosed with CD from 2004 to 2019 and had abdominal CT just prior to being diagnosed with CD were included in the CD group. Patients (≤18 years old) who were diagnosed with infectious enterocolitis from 2018 to 2019 and had undergone CT prior to being diagnosed with enterocolitis were included as a control group. We assessed the diagnostic performances of initial CT and laboratory findings for the diagnosis of CD using logistic regression and the area under the curve (AUC).ResultsIn total, 107 patients (50 CD patients, 57 control patients) were included, without an age difference between groups (median 13 years old vs. 11 years old, p=0.119). On univariate logistic regression analysis, multisegmental bowel involvement, mesenteric vessel engorgement, higher portal vein/aorta diameter ratio, longer liver longitudinal diameter, lower hemoglobin (≤12.5 g/dL), lower albumin (≤4 g/dL), and higher platelet (>320×10³/µL) levels were significant factors for CD. On multivariate analysis, multisegmental bowel involvement [odds ratio (OR) 111.6, 95% confidence interval (CI) 4.778–2605.925] and lower albumin levels (OR 0.9, 95% CI 0.891–0.993) were significant factors. When these two features were combined, the AUC value was 0.985 with a sensitivity of 96% and specificity of 100% for differentiating CD.ConclusionMultisegmental bowel involvement on CT and decreased albumin levels can help differentiate CD from infectious enterocolitis in children prior to a definite diagnosis of CD.