OBJECTIVE To explore the mechanism of pomegranate peel in improving non-alcoholic steatohepatitis (NASH) based on network pharmacology and cell experiments verification. METHODS Using the Traditional Chinese Medicine System Pharmacology Database(TCMSP) to obtain the active components of pomegranate peel and their corresponding targets. NASH-related disease targets were obtained from five disease databases, including the Human Gene Database(GeneCards), etc. To screen the targets of pomegranate peel and NASH and obtain the common targets through Venn diagrams. The protein-protein interaction network of pomegranate peel-NASH was constructed using the protein interaction database(STRING), and the “pomegranate peel-component-target-NASH” network was established with Cytoscape 3.7.1. Gene ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed using Metascape software. Finally, the effect of the main active components in pomegranate peel on NASH was observed with human hepatoma cells(HepG2). RESULTS There were 7 active ingredients in pomegranate peel, 191 target genes, 1 818 NASH targets, and 98 intersection targets. Topological analysis showed that the core components of pomegranate peel in the treatment of NASH were quercetin, kaempferol, and luteolin, and the core targets were protein kinase B(Akt1), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor(TNF). KEGG pathway analysis predicted that pomegranate peel treatment of NASH mainly involved phosphatidylinositol-3-kinase(PI3K)/Akt, nuclear factor kappa B(NF-κB), and other signaling pathways. The results of in vitro cell experiments showed that the expression levels of phosphorylated protein kinase B(p-Akt), IL-6 and other proteins were elevated in the model group compared with the control group(P<0.05). Compared with the model group, the active ingredients of pomegranate peel could significantly reduce the expression level of p-Akt and IL-6(P<0.05), as well as the mRNA expression level of IL-6 and TNF-α(P<0.05). CONCLUSION Pomegranate peel can exert anti-NASH effects through multiple components, multiple targets, and multiple pathways. The mechanism may be related to the active components quercetin, kaempferol, and luteolin in pomegranate peel affecting core targets such as Akt1 and regulating PI3K/Akt, NF-κB, and other signaling pathways, thereby inhibiting the expression of related inflammatory factors.

OBJECTIVE:To explore the effects and safety of dexmedetomidine combined with remifentanil on postoperative cognition and hemodynamics in patients underwent colon cancer surgery.METHODS:One hundred undergoing colon cancer sur gery in our hospital during Jun.2013-Apr.2016 were selected and divided into control group and observation group according to random number table,with 50 cases in each group.Control group was given Remifentanil hydrochloride for injection 2-4 μg/kg for anesthesia induction,with maintenance dose of 0.5-2 μg· kg/min;observation group was treated with Dexmedetomidine hydrochloride for injection 0.5 μg/kg and remifentanil 2-4 μg/kg for anesthesia induction,with maintenance dose of Dexmedetomidine hydrochloride for injection 0.4 μg·kg/h+Remifentanil hydrochloride for injection 0.5-2 μg·kg/min.MMSE score and the incidence of postoperative cognitive dysfunction (POCD) were observed in 2 groups 1,2,3 d after surgery,and the occurrence of ADR was record ed.RESULTS:The incidence of POCD in observation group 1,2,3 d after surgery were 16.0％,4.0％,6.0％,which was signifi cantly higher than 36.0％,12.0％,10.0％ of control group,with statistical significance (P＜0.05).There was no statistical significance in MMSE score between 2 groups 1,3 d after operation (P＞0.05).2 d after surgery,MMSE score of observation group was significantly higher than that of control group,with statistical significance (P＜0.05).There was no statistical significance in hemodynamic indexes,the incidence of ADR as blood pressure increasing,amyostasia,nausea and vomiting between 2 groups 1,2,3 d after surgery (P＞0.05).CONCLUSIONS:Dexmedetomidine combined with remifentanil can significantly improve postoperative POCD in patients underwent colon cancer surgery and have little effect on hemodynamics with good safety.

Objective:To explore the dose distribution characteristics between RapidArc and five-field intensity modulated radiotherapy(5F-IMRT) plans in the treatment of locally advanced pancreatic carcinoma,and to provide reference for selecting the appropriate radiation technique in clinic.Methods:Ten patients with locally advanced pancreatic carcinoma were selected.The patients were scanned by simulation CT, and the targets and organs at risk were contoured. RapidArc plan and 5F-IMRT plan were designed respectively.The treatment time and the differences of dose distribution in the targets and organs at risk of RapidArc and 5F-IMRT plans were compared.Results:The conformal index (CI) of RapidArc plan was superior than that of 5F-IMRT plan(P=0.01).The homogeneity index (HI) of targets were similar between two plans (P>0.05).RapidArc plan decreased the maximum dose (Dmax) of the spinal cord(P=0.005);RapidArc plan decreased the mean dose(Dmean) of stomach(P=0.019);5F-IMRT plan decreased the V20 of kidney(P=0.043);RapidArc plan decreased the mean dose(Dmean) of small intestine(P=0.011).The small intestine V10 and V20 of RapidArc plan were lower than those of 5F-IMRT plan(P=0.015,P=0.14);the monitor unit (MU) of RapidArc plan was significantly lower than that of 5F-IMRT plan,with a 18% reduction from the MU level of the latter one,and the treatment time was reduced by 70.3%.RapidArc plan had the smaller doses at liver and kidney compared with 5F-IM RT plan.Conclusion:For the patients with locally advanced pancreatic carcinoma,RapidArc plan has higher CI. RapidArc plan shows the advantages in the protection of organs.Compared with 5F-IMRT,RapidArc plan has less treatment time and significantly improves the curative efficiency.In clinic, the RapidArc plan is recommended.

Objective To investigate the consensus and controversies on the delineation of radiotherapy target volume for patients with locally advanced non-small cell lung cancer (LA-NSCLC).Methods Questionnaires including 15 questions on the delineation of radiotherapy target volume of NSCLC were sent to 12 radiation departments in China in November 2015.A patient with LA-NSCLC was selected by Fudan University Shanghai Cancer Center, and simulation CT images and medical history data were sent to the 12 radiation departments.Twelve radiation oncologists from the 12 radiation departments showed and explained the delineation of radiotherapy target volume of their own, and the patient was discussed by all experts in the sixth multidisciplinary summit forum of precise radiotherapy and chemotherapy for tumor and lung cancer.Results All receivers of the questionnaire answered the questions.The standard lung window width/level for the delineation of lung cancer was 800-1600/-600 to-750 HU, and the mediastinum window was 350-400/20-40 HU.Respiratory movement was measured by stimulator, 4D-CT, and stimulator+4D-CT with 2-5 mm expansion based on experience.The primary clinical target volume (CTV) was defined as gross target volume (GTV) plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma.The metastatic lesion of mediastinal lymph nodes was delineated as 5 mm plus primary lesion in 6 departments and as primary lesion in another 6 departments.Of the 12 departments, 10 applied 5 mm of set-up error, 1 applied 3 mm, and 1 applied 4-6 mm.For V20 of the lungs, 10 departments defined it as<30%, 1 as<35%, and 1 as 28%.Nine departments defined the radiation dose of concurrent chemoradiotherapy (CCRT) for LA-NSCLC as 60 Gy in 30 fractions, 62.7 Gy in 33 fractions in 1 department, 50-60 Gy in 25-30 fractions in 1 department, and 60-70 Gy in 25-30 fractions in 1 department.For the delineation of target volume for the LA-NSCLC patient treated with CCRT, the primary planning target volume (PTV) was defined as GTV plus organ movement (IGTV) and set-up error (GTV→IGTV→PTV) in 3 departments, as CTV plus organ movement (ITV) and set-up error (GTV→CTV→ITV→PTV) in 8 departments, and as CTV plus set-up error/IGTV plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma (CTV) and set-up error (GTV→CTV→PTV/GTV→IGTV→CTV→PTV) in 1 department.For the delineation of PTV in the mediastinal lymph node, GTV→IGTV→PTV was performed in 3 departments, GTV→CTV→ITV→PTV in 8 departments, and GTV→CTV→PTV in 1 department.For 10%-100% patients with LA-NSCLC, the radiation field needed to be replanned when 38-50 Gy was completed.There was no unified standard for the optimal standardized uptake value (SUV) of positron emission tomography (PET)-computed tomography (CT) simulation and delineation.Seven departments had applied magnetic resonance imaging (MRI) simulation and 10 departments had applied stereotactic body radiation therapy (SBRT) for the treatment of early-stage NSCLC.For the delineation of PTV for early-stage NSCLC (T1-2N0M0), GTV→IGTV→PTV was performed in 5 departments, IGTV→PTV in 3 departments, and GTV→CTV→ITV→PTV in 2 departments.In all the 12 departments, peripheral early-stage NSCLC was given 6.0-12.5 Gy/fraction, 3-12 fractions and central early-stage NSCLC was given 4.6-10.0 Gy/fraction, 5-10 fractions.The results of discussion on the delineation of target volume for the patient were as follows:respiratory movements should be measured by 4D-CT or simulator;the lung window width/level is 1600/-600 HU and the mediastinal window width/level is 400/20 HU;the primary controversy is whether the involved-field irradiation or elective nodal irradiation should be used for the delineation of CTVnd in the mediastinal lymph node.Conclusions Basic consensus is reached for the delineation of target volume in LANSCLC in these aspects:lung window width/level, respiratory movements and set-up error, primary lesion delineation, the radiation dose in CCRT, and the optimal time for replanning the radiation field.There are controversies on the optimal SUV in the delineation of target volume based on PET-CT simulation, the optimal dose fractionation in SBRT for early-stage NSCLC, and the delineation of CTVnd.

Objective To explore the relationship between first trimester pregnancy infection and congenital malformation in the cardiovascular system.Methods A hospital-based study was conducted from June 2014 to June 2016.Totally 1618 mothers of infants with cardiovascular system malformation and normal infants were interviewed through a face-to-face questionnaire survey.A propensity score-matched study was conducted to investigate the association between first trimester pregnancy infection and congenital malformation in the cardiovascular system.Results All important covariates were balanced after matching.First trimester pregnancy infection increased the risk of congenital malformation in the cardiovascular system,single congenital malformation in the cardiovascular system and multi-congenital malformation in the cardiovascular system.After matched,the OR values were 1.65 (95％ CI:1.21-2.24;P=0.001),1.50 (95％ CI:1.02 2.20;P=0.037),and 1.90 (95％ CI:1.18-3.06;P=0.008),respectively.Conclusion First trimester pregnancy infection increases the risk of congenital malformation in the cardiovascular system.Avoiding infectious diseases during the first trimester in pregnancy is important in decreasing the incidence of congenital malformation in the cardiovascular system.

Objective To explore the relationship of four kinds of lifestyle factors,namely,prenatal passive smoking,hair dyeing or perming,exposure to noise,living in a house renovated in the past one year,with congenital heart disease.Methods A hospital-based case-control study was conducted.Totally 270 mothers in the case group and 1633 mothers in the control group were interviewed through a face-to-face questionnaire survey.A generalized linear model was employed to investigate the association between congenital heart disease and prenatal lifestyle factors.Results Both in Model 1 and Model 2,prenatal hair dyeing or perming had no association with congenital heart disease.On the other hand,prenatal passive smoking,exposure to noise and living in a house renovated in the past one year all increased the risk of congenital heart disease.After adjustment for all confounders,the OR values were 1.771 (95％ CI:1.079-2.909),2.079 (95％ CI:1.310-3.298),and 2.494 (95％ CI:1.511-4.116),respectively.Conclusion Prenatal passive smoking,exposure to noise and living in a house renovated in the past one year are the risk factors for congenital heart disease.It is very important to avoid such factors during pre-pregnancy and pregnancy.

Objective To analyze the difference of dosimetry and evaluate clinical efficacy and acute toxicity reaction between RapidArc and fixed gantry angle dynamic intensity modulated radiotherapy (IMRT) in advanced cervical carcinoma.Methods A total of 43 patients with locally advanced cervical cancer were studied,including 22 patients treated with RapidArc and 21 patients with IMRT.All plans were prescribed 50.4 Gy in 28 fractions.The conformity index and homogeneity index of the targets,the monitor units(MUs) and delivery time were compared.Incidence of acute intestinal and bladder side effects and rates of efficacy were calculated.Results The conformity index of RapidArc was better compared to IMRT.The V40 and V50 of bladder and V30,V40 and V50 of rectum planned by RapidArc was significantly lower than that by IMRT(t =-2.386,-2.397,P ＜0.05;t =-5.525,-2.883,-2.686,P ＜0.05).The mean dose of femoral head planned by RapidArc was also significantly lower (t =-2.395,P ＜ 0.05).For RapidArc,mean MU and treatment time were reduced by 53.15％,and 62.14％,respectively.There was no difference in the incidence of acute intestinal and bladder toxicity and rates of complete remission and efficacy between the two groups.Conclusions In dosimetric analysis,RapidArc showed advantage in protecting organs at risk and reducing treatment time in radical radiotherapy for locally advanced cervical carcinoma.

Objective To evaluate the therapeutic effect of adipose-derived mesenchymal stem cells on radiation enteritis.Methods A total of 52 male Sprague-Dawley rats were used in the present study.Herein,46 rats were randomly selected and irradiated with a dose of 15 Gy at their abdomens.Two hours post-irradiation,23 rats were randomly selected and infused intraperitoneally with adipose-derived mesenchymal stem cells in passage 6 from young-female donor.The other 23 rats were intraperitoneally infused with PBS.The rest 6 rats were set as normal control.During the first 10 days post-irradiation,peripheral blood-samples from irradiated rats were harvested for testing the levels of IL-10 in serum using ELISA assay.Additionally,after isolating the thymic cells and peripheral blood mononuclear cells,the percentages of CD4/CD25/Foxp(3)-positive regulatory T cells in thymus and peripheral blood were tested by flow-cytometry.Finally,infiltration of inflammatory cells and deposition of collagens within irradiated small intestine were analyzed by H&E staining and Masson Trichrome staining,respectively.Based on the MPO-immunohistochemistry staining,the type of infiltrated cells was identified.The Kaplan-Meier method was used for analyzing the survival rate of irradiated rats.Results During a period of 30 days post-irradiation,the irradiated rats receiving adipose-derived mesenchymal stem cells survived longer than those receiving PBS (t =4.53,P ＜ 0.05).Compared to the irradiated rats with PBS-treatment,adipose-derived mesenchymal stem cells could elevate the level of IL-10 in serum (7 d:t =13.93,P ＜ 0.05) and increase the percentages of CD4/CD25/Foxp(3)-positive regulatory T cells in both peripheral blood (3.5 d:t =7.72,7 d:t=11.11,10 d:t =6.99,P ＜0.05) and thymus (7 d:t =16.17,10 d:t =12.12,P＜ 0.05).Moreover,infiltration of inflammatory cells and deposition of collagens within irradiated small intestine were mitigated by adipose-derived mesenchymal stem cells.Conclusions Adipose-derived mesenchymal stem cells were capable of curing radiation enteritis.

Objective To assess the therapeutic effect of human adipose-derived mesenchymal stem cells on radiation-induced vascular injury in the small intestine of rat. Methods A total of 34 male Sprague-Dawley rats were enrolled in this study. To establish a model of radiation-induced intestinal injury, each rat was irradiated with 15 Gy in whole abdomen. 17 rats were randomly selected and infused intraperitoneally with passage 6 ( P6 ) Ad-MSCs, and the other 17 rats that received PBS were set as control. 10 days post-irradiation, the number of CD31+ endothelial cells in the small intestine villus was measured by flow-cytometry, the expressions of CD31, CD105 and isolectin-B4 in the na?ve endothelial cells with detected by IHC-staining, and the vascular integrity was evaluated by measuring VE-Cadherin. The origination of na?ve endothelial cells within injured intestine was also analyzed. In addition, total mRNA were extracted from irradiated small intestine to assay the expressions of VEGF, bFGF, Flk-1 and SDF-1 using quantitative Real-time PCR. Results Compared to the control, the amount of CD31-postive endothelial cells within irradiated intestine was significantly increased after Ad-MSCs infusion ( t=12?15, P<0?05). The microvascular density in the injured sites was also significantly increased by the infusion of Ad-MSCs (20 d:t=10?33, P<0. 05;30 d:t=32?85, P<0?05). Moreover, the expressions of VEGF, bFGF, Flk-1 and SDF-1 were significantly up-regulated after delivery of Ad-MSCs ( VEGF:t =10?34, bFGF:t=11?25,Flk-1:t=6?73, SDF-1:t=6?73, all P<0?05), which was beneficial in maintaining the integrity of intra-villus blood-vessels as well as promoting neovascularization in the injured sites. Conclusion Ad-MSCs had potentials in healing radiation-induced vascular injury in rat small intestine.

Objective:To evaluate the performance of RapidArc technique on cervical cancer patients with various filling status of the bladder. Methods: Conventional fixed field intensity modulation radiated therapy (IMRT) is used as the benchmark. In 10 fe-males suffering from cervical cancer, two CT scans were performed for treatment planning:one with an empty bladder and the other with filled bladder. The prescribed dose was 50 Gy. The images of that with an evacuated bladder and that with filled bladder were planned in the dual-arc RapidArc and the 7-field IMRT, respectively. The implementor of the plan was the Varian TrueBeam linear ac-celerator. Dose-volume histogram was used to evaluate the data from each plan. Results:When the bladder was filled, IMRT and Rapi-dArc homogeneity were 1.05 and 1.04 (P>0.05), respectively. When the bladder was emptied, the homogeneity was 1.04 for both plans (P>0.05). With or without bladder filling, the conformity index was 0.71 and 0.73 for IMRT and RapidArc (P>0.05), respectively. The effect of V30 and V40 (volume for receiving doses of 30 and 40 Gy) on the intestine and the bladder was more favorable in a full than in an empty bladder. No significant difference between the two plans was observed. IMRT exhibited improved V30 on the rectum and on the bladder. RapidArc was much better in terms of monitor unit (MU) and deliver time. Conclusion:No significant differences in the homogeneity and conformity index between dual-arc RapidArc and 7-field IMRT were observed. Filled bladder is better than empty bladder in intestine and bladder protection in both RapidArc and IMRT. IMRT is better on V30 of the rectum and the bladder, whereas RapidArc improved MU and deliver time.