Genetic Variants in EGFR/PLCE1 Pathway Are Associated with Prognosis of Esophageal Squamous Cell Carcinoma after Radical Resection

Esophageal cancer (EC) is one of the most deadly malignant diseases. Several studies revealed that variations of the phospholipase C epsilon 1 (PLCE1) gene were associated with EC susceptibility. PLCE1 is located downstream of the epidermal growth factor receptor (EGFR) pathway. Presently, the single nucleotide polymorphisms (SNPs) of EGFR/PLCE1 genes and their associations with EC survival remain unclea匚 In this study, the associations between genetic variants in the EGFR/PLCE1 pathway and prognosis in 124 esophageal squamous cell carcinoma (ESCC) patients with radical resection were explored. The results showed that CC genotype of both PLCE1 rsl7109671 and EGFR rs2072454 was associated with ESCC prognosis. Multivariate analysis revealed that patients with the two unfavorable genotypes had the worst overall survival (OS) or disease-free survival (DFS)(HR=6.099, 95%CI=1.903-19.552;HR=3.994, 95%CI=1.49-10.702, respectively). Additionally, combination of SNPs and tumor stage could better predict OS (for AUC, 0.774 vs. 0.709) and PFS (for AUC, 0.773 vs. 0.704) than tumor stage alone.In conclusion, genetic variants of the EGFR/PLCE1 may be predictors of the prognosis of ESCC after surgery. The individuals with the CC genotype of PLCE1 rsl7109671 and EGFR rs2072454 should receive more aggressive treatments.

Computed tomography combined with gastroscopy for assessment of pancreatic segmental portal hypertension

BACKGROUND Pancreatic segmental portal hypertension(PSPH) is the only type of portal hypertension that can be completely cured. However, it can easily cause varicose veins in the esophagus and stomach and hemorrhage in the digestive tract.AIM To explore the application of computed tomography(CT) to examine the characteristics of PSPH and assess the risk level.METHODS This was a retrospective analysis of CT images of 22 patients diagnosed with PSPH at our center. Spearman correlation analysis was performed using the range of esophageal and gastric varices(measured by the vertical gastric wall), the ratio of the width of the splenic portal vein to that of the compression site(S/C ratio), the degree of splenomegaly, and the stage determined by gastroscopy. This study examined whether patients experienced gastrointestinal bleeding within 2 wk and combined CT and gastroscopy to explore the connection between bleeding and CT findings.RESULTS The range of esophageal and gastric varices showed the best correlation in the diagnosis of PSPH(P < 0.001), and the S/C ratio(P = 0.007) was correlated with the degree of splenomegaly(P = 0.021) and PSPH(P < 0.05). This study revealed that male patients were more likely than females to progress to grade 2 or grade 3 as determined by gastroscopy. CT demonstrated excellent performance, with an area under the curve of 0.879.CONCLUSION CT can be used to effectively analyze the imaging signs of PSPH, and CT combined with gastroscopy can effectively predict the risk level of gastrointestinal bleeding.

Prediction of quality markers of traditional Chinese medicines based on network pharmacology

Network pharmacology is a powerful tool to reflect the pharmacologically active effects,mechanism of action and toxic activity of traditional Chinese medicines(TCMs).The ingredients of TCMs,associated with quality control of TCM products,are those fundamental chemicals that exhibit biological activities.A great amount of effort has been made by scientists in that field in order to improve the quality of TCMs,though the approaches to determine their quality and the TCM theory and compatibility rules remain ambiguous.Now some methods and technologies must be applied to predict and explore the quality marker(Q-marker)for quality control,as well as to clarify the factors affecting the quality of TCM,which may give new insight into rational ground of establishment of appropriate quality control and assessment system.In this review paper,authors focus on the prediction of quality markers of TCMs by network pharmacology based on three aspects:(1)from network medicine to network pharmacology,(2)complex network system of traditional Chinese medicine,and(3)predicting TCM quality markers based on network pharmacology.Authors proposed the research pattern on network pharmacology based on biological and medical networks,and further TCM network pharmacology based on substantial basis of TCM formulae,and the idea of"effect-ingredient-target-fingerprint"to predict and recognize the TCM Qmarker was the ultimate goal.In addition,authors yet noted how to make full use of the advantages of network toxicology to provide new ideas for the toxicity study of complex TCM systems and the prediction of TCM toxicity markers.

Morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5-hydroxytryptophan production in the gut microbiota

Morinda officinalis oligosaccharides(MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan(5-HTP) → serotonin(5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan;meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation,and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood-brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide,as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota.

Prediction of intravenous immunoglobulin resistance in Kawasaki disease in children

Background We aimed to explore predictive measures for intravenous immunoglobulin(IVIG)resistance in children with Kawasaki disease(KD).Methods Patients diagnosed with KD were enrolled in this study.Univariate analysis and multiple logistic regression were utilized to analyze the clinical features and laboratory results prior to IVIG-treatment of the two groups.Independent predictors of IVIG resistance were analyzed,and a predictive model for KD children with IVIG resistance was constructed.Results A total of 277 children with KD,180 boys and 97 girls,aged 2-128(median 23)months,were enrolled in the study.Compared with the IVIG-responsive group,the IVIG-resistant group had higher levels of the peripheral neutrophil count,mean platelet volume,mean platelet volume-to-lymphocyte ratio and C-reactive protein,and total serum bilirubin,but lower levels of peripheral lymphocyte count,serum albumin and serum prealbumin.Age(in months),peripheral neutrophil count,lymphocyte count and mean platelet volume and serum albumin were independent indicators for IVIG resistance by multivariate logistic regression analysis.A logistic regression model and a scoring system were set up,where cut-off values of—0.46 and 6.5 points yielded sensitivities of 83.9%and 77.4%,and specificities of 74.8%and 61.0%,respectively.The areas under the curve(AUC)were 0.808 in the logistic regression model,and 0.750 in the scoring system.Conclusion Our model for predicting IVIG-resistant children with KD,involving age(months),peripheral neutrophil count,lymphocyte count and mean platelet volume and serum albumin prior to IVIG-treatment,is helpful for clinical prediction of children with IVIG-resistant KD.

Design,synthesis and biological activity of cyclohexane-bearing C-glucoside derivatives as SGLT2 inhibitors

Seven cyclohexane-bearing C-glucoside derivatives（7,9,12,13 and 17-19） were designed and synthesized as SGLT2 inhibitors starting from a potent SGLT2 inhibitor we discovered in earlier work, （lS）-1-deoxy-l-[4-methoxy-3-（trans-n-propylcyclohexyl）methylphenyl]-D-glucose（1）.The in vitro and in vivo biological activities were evaluated by hSGLT2/hSGLTl inhibition and urinary glucose excretion （UGE）,respectively.Among the synthesized compounds 12,the 6-deoxy derivative of 1 was the most active and selective SGLT2 inhibitor（IC_（50）= 1.4nmol/L against hSGLT2;selectivity = 1576）.Compound 12 was a potent SGLT2 inhibitor,which could induce more urinary glucose than 1 and dapagliflozin in UGE.

Baseline left ventricular ejection fraction associated with symptom improvements in both children and adolescents with postural tachycardia syndrome under metoprolol therapy

Background:Postural tachycardia syndrome(POTS)is a common childhood disease that seriously affects the patient’s physical and mental health.This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS.Methods:This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019.All patients had completed a standing test or basic head-up tilt test and cardiac echocardiography before treatment.Treatment response was evaluated 3 months after starting metoprolol therapy.The pre-treatment baseline LVEF and LVFS values were evaluated for correlations with decreases in the symptom score after treatment(DSS).Multivariable analysis was performed using factors with a P value of<0.100 in the univariate analyses and the demographic characteristics.Results:A comparison of responders and non-responders revealed no significant differences in demographic,hemodynamic characteristics,and urine specific gravity(all P>0.050).However,responders had significantly higher baseline LVEF(71.09%±4.44%vs.67.17%±4.88%,t=2.789,P=0.008)and LVFS values(40.00[38.00,42.00]%vs.36.79%±4.11%,Z=2.542,P=0.010)than the non-responders.The baseline LVEF and LVFS were positively correlated with DSS(r=0.378,P=0.006;r=0.363,P=0.009),respectively.Logistic regression analysis revealed that LVEF was independently associated with the response to metoprolol therapy in children and adolescents with POTS(odds ratio:1.201,95%confidence interval:1.039–1.387,P=0.013).Conclusions:Pre-treatment baseline LVEF was associated with symptom improvement after metoprolol treatment for children and adolescents with POTS.

Molecular Simulation Study on Bentysrepinine Metabolites Improving Binding Affinity of HBV DNA Polymerase

Objective To study the effect of bentysrepinine（Y101） metabolites on improving binding affinity of HBV DNA polymerase. Methods The binding mode of Y101 and its metabolites with DNA polymerase has been driven by hydrophobic interaction. Results Two compounds, T2 and T4, exhibited the improvement of the binding affinity to HBV DNA polymerase protein, which suggests that the inhibitory activity against HBV DNA polymerase protein can be enhanced. Conclusion The variant docking poses of T2 and T4 might imply the novel recognition of inhibitory effects of T2 and T4, in comparison with Y101.

Impact of comorbidities on the prognosis of pediatric vasovagal syncope

Vasovagal syncope(VVS)is the primary entity of neurally mediated syncope(NMS)in childhood,and its prognosis is usually considered benign.However,it is found in clini-cal practice that some children with VVS appear to have a frequent recurrence of syncope and poor response to treat-ment[1],which might seriously affect their quality of life[2].In recent years,an increasing number of comorbidities of VVS have been reported.Liao et al.found that 31%of pediatric patients with NMS suffered from allergic disease[3],and Vallejo M reported that more than 50%of patients had headaches[4].These comorbidities might make the clinical manifestations even more complex.However,until now,it has been unclear whether comorbidities are associated with the prognosis of children and adolescents suffering from VVS.Therefore,the present study was conducted to examine whether there is any impact of comorbidities on the prognosis of pediatric VVS to better understand the outcome and management of children and adolescents with VVS.