Bone marrow mesenchymal stem cells (BMSCs) have been shown to be multipotent cells that possess high self-replicating capacity. The purpose of our study was to investigate the feasibility of using enteric neuron-like cells obtained by in vitro induction and differentiated from rat BMSCs for the treatment of Hirschsprung's disease (HD). Glial cell-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) are neurotrophic factors that play important roles in neuronal development, differentiation, survival and function. Meanwhile, GDNF mutations are a major cause of HD. In this study, BMSCs were transfected with eukaryotic expression plasmids co-expressing GDNF and NT-3, and the transfected cells displayed neuron-like changes after differentiation induced by fetal gut culture medium (FGCM). Immunofluorescence assay showed positive expression of the neuronal marker NSE and the enteric neuronal markers PGP9.5, VIP and nNOS. Reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of GDNF and NT-3 in transfected BMSCs. The present study indicates that genetically modified BMSCs co-expressing GDNF and NT-3 are able to differentiate into enteric neuronal cells and express enteric nerve markers when induced by FGCM. This study provides an experimental basis for gene therapy to treat enteric nervous system-related disorders, such as HD.

Objective To explore the effects of lipoxinA4 on expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in rat primary lung fibroblast cells (LF) after lipopolysaccharide (LPS) challenge.Methods Primary lung fibroblast cells were incubated with various concentrations (0.1,1,10 μg/mL) of LPS for different lengths of time (3,6,9 h).Then primary lung fibroblast cells were still incubated in DMEM medium containing LPS in the presence or absence of lipoxinA4.After incubation,the supematant of medium was collected and the level of PGE2 was detected by using ELISA.The cells were harvested,and COX-2 protein was analyzed by Western blot.Results The model of acute inflammation in fibroblasts was well established by administering 1 μg/mL LPS in fibroblasts for 6 hours.Induction of COX-2 protein by LPS was inhibited by lipoxinA4.The levels of PGE2 in control group,LPS group and LPS + LipoxinA4 group were 55.84 pg/mL,411.73 pg/mL and 307.07 pg/mL,respectively,and there was a significantdifference between LPS group and LPS + LipoxinA4 group (P ＜0.01).Conclusion LipoxinA4 down-regulates the expression of the COX-2 induced by LPS in primary lung fibroblast cells and consequently inhibits the production of PGE2 in a dose dependent manner.

Objective To investigate the influence of diabetes mellitus (DM) on left ventricular(LV) remodeling in patients with acute ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) within 12 hours of symptom onset. Methods Four hundred and fifty-one consecutive patients with acute STEMI treated by primary PCI were prospectively enrolled in the current study. Baseline, angiographic and PCI features and prevalence of LV remodeling at one-week during hospitalization and 6-month clinical follow-up by two-dimensional echocardiography were compared between 93 diabetic and 358 non-diabetic patients. Results Despite similar baseline clinical and angiographic characteristics, symptom-to-door time was longer (399±106 min vs. 321±116 min, P=0.006) and prevalence of multivessel disease was higher (65.6%vs. 51.7%, P=0.02) in diabetic patients. More patients in diabetic group had LV remodeling at 6-month clinical follow-up (29.0%vs. 17.3%, P=0.01), and DM was an independent predictor of LV remodeling (RR 2.1, 95%CI 1.31-4.79, P=0.02). The rate of rehospitalization due to heart failure did not differ between diabetic and non-diabetic patients (12.9%vs. 8.1%, P=0.15), however, more adverse events occurred in patients with LV remodeling comparing to those without LV remodeling (25.8% vs. 6.6%, P < 0.001). Conclusions Diabetic patients with STEMI often have an increased risk of LV remodeling after treated by primary PCI. Thus, comprehensive therapeutic strategy for diabetic patients presented with STEMI is required considering the poor prognosis of these patients with LV remodeling.

Objective To investigate the effect of methylene blue (MB) on oxygen metabolism in patients with septic shock. MethodsForty ASA Ⅱ or Ⅲ patients with septic shock aged 38-64 yr weighing 48-75 kg undergoing emergency surgery were randomly divided into 2 groups ( n = 20 each): group Ⅰ norepinephrine (group NE) and group Ⅱ MB. The patients were unpremedicated. Anesthesia was induced with midazolam, etomidate,sufentanil and vecuronium and maintained with inhalation of 0.5％-1.5％ sevoflurane and intermittent iv boluses of sufentanil and vecuronium. The patients were mechanically ventilated after tracheal intubation. PETCO2 was maintained at 35-45 mm Hg. During operation MB was infused at 0.5-1.0 mg·kg-1·h-1 in group MB and NE at 0.5-2.0 μg· kg-1 · min-1 in group NE respectively to maintain hemodynamic stability. Radial artery was cannulated and connected with Vigileo cardiac output monitor. Right internal jugular vein was cannulated for CVP monitoring.HR, SvO2, MAP, CVP, SV and CI were continuously monitored. Arterial and central venous blood samples were collected simultaneously before induction of anesthesia (T0, baseline), immediately before (T1) and at 30, 60 and 90 min after skin incision (T2-4) and at the end of operation (T5) . Blood gas analysis was performed. O2 consumption index (VO2I), O2 delivery index (DO2I) and O2 extraction rate (ERO2) were calculated. Blood lactate concentration was measured. Results MAP, HR, CVP, SVRI, DO2I, VO2I and ERO2 were significantly higher,while CI and blood lactate concentration lower during operation (T2-5) in group MB than in group NE. MAP, HR,CVP, SVRI, VO2I, DO2I, and ERO2 were significantly higher, while CI and blood lactate concentration were lower during operation (T2-5) as compared with the baseline values at T0 in group MB. In group NE there were no significant change in MAP, HR, CVP and DO2I during operation (T2-5 ) as compared with the baseline at T0. ConclusionIntravenous infusion of MB at 0.5-1.0 mg·kg-1·h-1 during operation may improve hemodynamics and oxygen metabolism in patients with septic shock.

Objective To evaluate the effects of lipoxin A4 (LXA4) on human type Ⅱ alveolar epithelial cell wound repair,proliferation and apoptosis.Methods Experiment Ⅰ Human type Ⅱ alveolar epithelial cells were inoculated in 24-well plates and divided into 4 groups (n=10 each) using a random number table:control group (group C),1 nmol/L LXA4 group (group L1),10 nmol/L LXA4 group (group L2) and 100 nmol/L LXA4 group (group L3).Cells were cultured in normal culture atmosphere in group C.Cells were incubated with 1,10 and 100 nmol/L LXA4 in L1,L2 and L3 groups,respectively.The scratch wound assay was performed at 36 h of culture or incubation.Cell proliferation was measured at 24 h of culture or incubation.Experiment Ⅱ Human type Ⅱ alveolar epithelial cells were inoculated in 96-well plates and divided into 5 groups using a random number table:control group (group C,n=10),Fas-ligand group (n =10),Fas-ligand+LXA4 group (n =10),Fas-ligand+TNF-α group (n =5) and Fas-ligand+TNF-α+LXA4 group (n=5).Cells were incubated with 100 ng/ml Fas-Ligand,100 ng/ml Fas-Ligand plus 100 nmol/L LXA4,100 ng/ml Fas-Ligand plus 100 ng/ml TNF-α,and 100 ng/ml Fas-Ligand plus 100 ng/ml TNF-α plus 100 nmol/L LXA4 in Fas-ligand,Fas-ligand+LXA4,Fas-ligand+TNF-α,and Fas-ligand +TNF-α+LXA4 groups,respectively.The cell viability was measured at 24 h of culture or incubation.Cell apoptosis was detected using the flow cytometry,and apoptosis rate was calculated in C,Fas-ligand and Fas-ligand+LXA4 groups.Results Experiment Ⅰ Compared with group C,the percentage of cell repair size and percentage of proliferation were significantly increased in L1,L2 and L3 groups (P＜0.05 or 0.01).Compared with group L1,the percentage of cell repair size and percentage of proliferation were significantly increased in group L3 (P＜ 0.01),and no significant change was found in the parameters mentioned above in group L2 (P＞0.05).Experiment Ⅱ Compared with group C,the cell viability was significantly decreased,and the apoptosis rate was increased in group Fas-ligand,the cell viability was significantly decreased in group Fas-ligand+TNF-α (P＜ 0.01),and no significant change was found in the cell viability or apoptosis rate in group Fas-ligand+LXA4 or in the cell viability in group Fas-ligand+TNF-α+LXA4 (P＞0.05).Compared with group Fas-ligand,the cell viability was significantly increased,and the apoptosis rate was decreased in group Fas-ligand+LXA4 (P＜ 0.05).The cell viability was significantly higher in group Fas-ligand +TNF-α + LXA4 than in group Fas-ligand +TNF-α (P ＜ 0.01).Conclusion LXA4 can promote human type Ⅱ alveolar epithelial cell wound repair and proliferation and inhibit the apoptosis.

Objective To analyse and compare the effects and safety of early use (in emergency room, intravenous loading followed by infusion) with bolus injection during primary PCI of tirofiban, on post-procedural TIMI flow and 30d clinical outcomes. Methods Seven hundred and seven patients with acute STEMI treated by primary PCI in Ruijin hospital were retrospectively and enrolled screened. Among them, 86 patients with single bolus intra-coronary injection of tirofiban (25 μg/kg) during the procedure were served as observation group. Baseline, angiographic, PCI features and rate of major adverse cardiac events (MACE) at 30 d follow-up were compared with those received early intravenous infusion of tirofiban (10ug/kg bolus followed by 0.15μg/(kg·min) intravenous infusion)(control group, n=239). Results Compared with control group, patients in observation group were older[(63.8±11.4) vs. (57.9±8.8), P=0.01], had higher prevalence of hypertension (58.6%vs. 51.0%, P=0.005), multivessel disease (57.0%vs. 34.3%, P<0.001), and female in gender (40.7%vs. 25.1%, P=0.006). Post-procedural TIMI flow in culprit vessel and TMP grade were comparable between the two groups (P=0.66 and P=0.48, respectively). Reduction in TIMI minimal bleeding events were found in the observation group (2.3%vs. 9.6%, P=0.03). MACE free survival rate at 30d clinical follow-up was similar between the two groups (P=0.48). Conclusions Single bolus intra-coronary injection of tirofiban exerts similar effects in post-procedural TIMI flow, TMP grade in culprit vessel and 30d clinical outcomes compared with early use in emergency room with intra-venous loading and infusion, nevertheless, intra-coronary injection resulted in significantly reduced TIMI minimal bleeding events. Prospective, randomized clinical study is mandatory to prove our current results.

Bone marrow mesenchymal stem cells (BMSCs) have been shown to be multipotent cells that possess high self-replicating capacity.The purpose of our study was to investigate the feasibility of using enteric neuron-like cells obtained by in vitro induction and differentiated from rat BMSCs for the treatment of Hirschsprung's disease (HD).Glial cell-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) are neurotrophic factors that play important roles in neuronal development,differentiation,survival and function.Meanwhile,GDNF mutations are a major cause of HD.In this study,BMSCs were transfected with eukaryotic expression plasmids co-expressing GDNF and NT-3,and the transfected cells displayed neuron-like changes after differentiation induced by fetal gut culture medium (FGCM).Immunofluorescence assay showed positive expression of the neuronal marker NSE and the enteric neuronal markers PGP9.5,VIP and nNOS.Reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of GDNF and NT-3 in transfected BMSCs.The present study indicates that genetically modified BMSCs co-expressing GDNF and NT-3 are able to differentiate into enteric neuronal cells and express enteric nerve markers when induced by FGCM.This study provides an experimental basis for gene therapy to treat enteric nervous system-related disorders,such as HD.

Objective: To understand the characteristics of sexual partners and the influence of having multiple sexual partners on substance use among young male students man who have sex with men (MSM) in China, and to provide scientific basis for the prevention and control of HIV/AIDS among young MSM students. Methods: A mixed recruitment method of snowball sampling and respondent driven sampling was used to recruit young MSM students in Beijing and Tianjin, and a questionnaire survey was conducted among 220 participants from November to December 2019. Chi-square test and generalized linear model multi-factor Logistic regression were used to analyze the influencing factors of substance use before sexual behavior. Results: The average age of them was (22.39±2.57) years old, 84.5% of them were students, the average age of first sexual behavior was (18.83±2.45) years old, 44.1% of them had two or more sexual partners (including fixed sexual partners, temporary sexual partners and commercial sexual partners), 22.7% had more than one male fixed partner. After adjusting for age and education, having multiple sexual partners was risk factor for drinking alcohol before sex (aOR=2.97) or substance abuse (aOR=2.39). Having male temporary sexual partner was an risk factor in substance use before sexual behavior(OR=4.10). Conclusion The characteristics of sexual partners among young MSM students are complex, and the proportion of multiple sexual partners is high. Having fixed single sexual partner can reduce the risk of substance use before sexual behavior. AIDS prevention education for young MSM students should be further strengthened.

Aiming at the lack of quantitative evaluation methods in clinical diagnosis of lung cancer, a classification and prediction model of lung cancer based on Support Vector Machine (SVM) was constructed by using radiomics method. Firstly, the definition and processing flow of radiomics were introduced. The experimental samples were selected from 816 lung cancer patients on LIDC. Firstly, ROI was extracted by central pooling convolution neural network segmentation method. Then, Pyradiomics and FSelector feature selection models were used to extract features and reduce dimension. Finally, SVM was used to construct the classification and prediction model of lung tumors. The predictive accuracy of the model is 80.4% for the classification of benign and malignant pulmonary nodules larger than 5 mm, and the value of the area under the curve (AUC) is 0.792. This indicates that the SVM classifier model can accurately distinguish benign and malignant pulmonary nodules larger than 5 mm.
Algorithms ; Humans ; Lung Neoplasms/diagnostic imaging* ; Neural Networks, Computer ; Radiometry ; Support Vector Machine ; Tomography, X-Ray Computed

Objective: To identify the characteristics of social network and the association between ego-centric network and HIV status among young MSM Chinese students. Methods: The cross-sectional study was conducted in Chongqing, Tianjin, Harbin and Xi an city from April to December 2017 and from March to May 2018. A mixed recruitment method of snowball sampling and RDS approach was used to recruit participants who reported information on social network and received HIV test. The Multiple Regression Analysis method was used to for the analysis of association between ego-centric social network and HIV status of men who have sex with men (MSM) among young students. Results: The sample included 547 participants who nominated 1 088 social partners in total with average age of 13 to 60 years old. The MSM with different sexual orientation from their social members (aOR=0.38), embedded in a large network (aOR=0.63), with a high individual betweenness centrality (aOR=0.27) were at lower risk of HIV-positive status; while MSM who differed greatly in education level with their social members(aOR=1.60), existed in sexual networks(aOR=1.41), existed in the “risky networks” (aOR=1.88) , with high network density (aOR=1.91) and a high individual degree (aOR=4.10) had higher risk of HIV-positive status(P<0.05). Conclusion MSM with great difference in education level from social members, existed in sexual networks, with a large network density and a high degree were exposed to higher risk of HIV-positive status.