1.Establishment of mouse models of focal cerebral ischemic reperfusion injury combined with diabetes mellitus and expression of relevant inflammatory factors
Kai SUN ; Xiuping ZHANG ; Linjie SONG ; Qingxia TAO ; Chong WANG
Chinese Journal of Neuromedicine 2016;15(2):123-129
Objective To establish the mouse models of focal cerebral ischemic/reperfusion (I/R) injury combined with diabetes mellitus (DM),and investigate the possible mechanism of brain injury.Methods Eighty healthy C57BL/6J mouse were randomly divided into normal group and DM group;normal saline or streptozotocin was given to the mice in the two groups via intraperitoneal injection,and the concentration of glucose in peripheral blood was measured at different time points (2,4,6 and 8 weeks after injection);and then,the mice in the two groups were subdivided into normal sham-operated group,normal I/R group,DM sham-operated group and DM+I/R group (n=20).The focal I/R models were induced by thread occlusion method;the neuroethology assessment was determined by Zea Longa method in the normal I/R group and DM+I/R group;the morphology of the brain tissues in the four groups was observed by HE staining;changes of mRNA expressions of interleukin (IL)-1β,IL-6 and tumor necrosis factor (TNF)-α were analyzed by quantitative real-time PCR.Results (1)The glucose concentration in DM group was stable at a high level within the 8 weeks;as compared with normal group,DM group had significantly higher glucose concentration at each time point (P<0.05).(2) The assessment scores of DM+I/R group (2.800±0.092) were significantly higher than those of I/R group (1.750±0.123,P<0.05).(3) Typical pathological changes were presented by HE staining,DM+I/R group presented worse damage to the brain as compared with normal I/R group.(4) Quantitative real-time PCR showed that the IL-1β and TNF-α mRNA expressions in the normal I/R group was significantly higher than those in the normal sham-operated group (P<0.05);the mRNA expressions of IL-1β,IL-6 and TNF-α in DM+I/R group were significantly increased as compared with those in the DM sham-operated and normal I/R group (P<0.05).Conclusion The simple and reliable focal cerebral I/R combined with DM models are successfully established;inflammation reaction mediated by inflammatory factors might play an important role in this aggravating damage.
2.Protective effect of anti-high mobility group box 1 on cerebral ischemia reperfusion injury in diabetic mice
Kai SUN ; Xiuping ZHANG ; Linjie SONG ; Qingxia TAO ; Chong WANG
Chinese Journal of Neuromedicine 2016;15(9):901-907
Objective To investigate whether cerebral ischemia reperfusion (I/R) injury combined with diabetes mellitus (DM) could elevate concentrations of serum high mobility group box 1 (HMGB 1) and its related inflammatory factors,and to explore the underlying mechanism of cerebral I/R injury combined with DM by blocking HMGB 1.Methods One hundred and forty healthy male C57BL/6 mice were randomly divided into four groups:normoglycemia (NG) group (n=25),NG+I/R group (n=25),hyperglycemia (HG) group (n=25),and HG+I/R group (n=65);40 mice in the HG+I/R group were chosen and divided into anti-HMGB1 group and IgG control group (n=20).High-fat feeding and i.p.injection of streptozotocin were used to establish HG mouse models,and then,middle cerebral artery occlusion was performed to establish the HG+I/R mouse models.Mice were treated with tail intravenous injection of 30 μg/g anti-HMGB 1 polyclonal antibody or control IgG 1 h before ischemia as previously described.After accomplishment of animal models,serum HMGB1 concentrations were evaluated by ELISA,the permeability of blood brain barrier (BBB) was observed by Evans-blue fluorescence quantitative method,quantitative real-time PCR was introduced to detect the mRNA expressions of interleukin (IL)-1β,IL-6,and inducible nitric oxide synthase (iNOS).Morphology changes of damaged brains were observed by HE staining.Results The serum HMGB 1 level in the HG+I/R group was significantly higher than that in the NG+I/R group (P<0.05).HG+I/R group had significantly higher BBB permeability than NG+I/R group (P<0.05),while anti-HMGB1 group had significantly lower BBB permeability than HG+I/R group (P<0.05).As compared with the NG group,the HG+I/R group had unclear cellular structures in the brain tissues with necrosis neurocytes and interstitial edema,while the cellular structures were obviously improved in the anti-HMGB1 group.Expressions ofIL-1β,IL-6 and iNOS in the HG+I/R group were significantly elevated as compared with those in the NG+I/R group (P<0.05),while those in the anti-HMGBl group had significantly decreased levels ofIL-1β and iNOS as compared with those in the HG+I/R group (P<0.05),and the IL-6 level showed no significant difference between the two groups (P<0.05).Conclusion The pathogenesis of DM could increase concentration of serum HMGB 1,and anti-HMGB 1 mAb could alleviate brain injury by blocking HMGB 1,and render a new promising therapeutic way for DM patients suffered with ischemic stroke.
3.Differentially expressed gene in nasopharyngeal carcinoma cell lines with various metastatic potentialities.
Linjie ZHANG ; Libing SONG ; Yinghong MA ; Bijun HUANG ; Qiwan LIANG ; Yixin ZENG
Chinese Journal of Oncology 2002;24(5):430-434
OBJECTIVETo investigate gene expression profile in nasopharyngeaL carcinoma (NPC) cell lines with different metastatic potentialities, in order to identify new candidate genes related to the development, progress and metastasis of NPC.
METHODSThe mRNA expressions of high metastatic NPC cell line 5-8F, tumorigenic but nonmetastatic NPC cell line 6-10B and non-tumorigenic NPC cell line 13-9B (3 sublines of SUNE-1) were investigated by cDNA microarray containing 14 000 cDNA clones. The alterations in gene expression levels were confirmed by reverse-transcription PCR.
RESULTSThere were 82 differentially expressed genes comparing 5-8F and 13-9B; 38 differentially expressed genes comparing 6-10B and 13-9B; 54 comparing 5-8F and 6-10B. There were 12 common differentially expressed genes comparing 6-10B, 5-8F and 13-9B; 14 common differentially expressed genes comparing 5-8F and 13-9B, 6-10B. The expressions of the above genes were involved in metabolism, transcription, differentiation, apoptosis and signal transduction.
CONCLUSIONThe gene expression profile in nasopharyngeal carcinoma cell lines is an important index in the search of new candidate genes related to NPC.
Cell Line ; DNA, Complementary ; analysis ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Neoplasm Metastasis ; genetics ; Oligonucleotide Array Sequence Analysis ; Tumor Cells, Cultured
4.Modified double-tract reconstruction operation in early SiewertⅡ esophagogastric junction adenocarcinoma
Yuchao MA ; Yanyang SONG ; Jianhong DONG ; Wanhong ZHANG ; Linjie LI
Chinese Journal of General Surgery 2022;37(2):90-93
Objective:To evaluate the safety and efficiency of a modified double-tract reconstruction procedure─proximal gastrectomy with piggyback interposed jejunal single-channel reconstruction (PJIR-STR) for early SiewertⅡ adenocarcinoma of esophagogastric junction (AEG).Method:Data of 8 SiewertⅡ AEG patients at Shanxi Tumor Hospital and undergoing PJIR-STR from May 2018 to Oct 2019 were retrospectively analyzed. The gastroesophageal reflux disease questionnaire (GerdQ) was used to score the patients at 3, 6, 12, and 18 months after surgery. The severity of postoperative reflux esophagitis was assessed by gastroscopy at 3, 6 months after surgery, using the Los Angeles Classification criteria.Result:All patients recovered well after surgery without serious complications. No obvious gastroesophageal reflux was observed in all patients at different periods (All of the GerdQ scores were <8 points.) The results of gastroscopy showed that 1 patient was diagnosed as grade B reflux esophagitis at 3, 6 months after surgery, which was responsive to conservative treatment, and the other 7 patients had no grade B or above reflux esophagitis.Conclusion:PJIR-STR is a feasible, safe reconstruction with excellent efficiency of dual anti-reflux for the SiewertⅡ AEG.
5.Study on the molecular mechanism of Linggui Zhugan Decoction in treating hypertension and obesity based on network pharmacology and molecular docking technology
Jixin LI ; Wenru WANG ; Yan REN ; Linjie QIU ; Xinzi SONG ; Haiyan REN ; Xiaoqing LIU ; Jin ZHANG
International Journal of Traditional Chinese Medicine 2023;45(4):456-463
Objective:To explore the material basis and mechanism of Linggui Zhugan Decoction in treating hypertension and obesity by means of network pharmacology and molecular docking technique.Methods:The TCMSP was retrieved and the main active components and action targets of Linggui Zhugan Decoction were screened. The GeneCards, OMIM, TTD, DisGeNET and DrugBank databases were used to screen disease-related targets of hypertension and obesity. The Cytoscape 3.9.0 was used to draw Chinese materia medica-composition-intersection target-disease network diagram. The STRING 11.5 database was used to draw PPI network. The cytoNCA plug-in was used to screen core active components and targets. The bioenrichment analysis of GO and KEGG was carried out in the R4.1.2, and the Chinese materia medica-intersection target-path diagram was drawn, and the core active components and core targets were docked in PyMOL and AutoDockTools 1.5.7.Results:A total of 102 potentially active components and 62 intersection targets were obtained, and 8 active components and 7 core targets were screened. Enrichment analysis showed that the key targets were mainly enriched through the signaling pathways of fluid shear stress and atherosclerosis, lipid and atherosclerosis, and AGE-RAGE, which were involved in biological processes such as the response to nutritional levels and the regulation of small molecule metabolism. Molecular docking showed that there were 37 groups with addinity < -7 kcal/mol.Conclusion:The main active components of Linggui Zhugan Decoction are quercetin, kaempferol and naringenin, which may play a role in fluid shear stress and atherosclerosis pathway, lipid and atherosclerosis pathway and AGE-RAGE signal pathway through AKT1, EGFR, IL1B and other targets.
6.Development and clinical evaluation of an equipment with artificial intelligence real-time assistance in detection of gastrointestinal protruding lesions under endoscopy
Zhiyin HUANG ; Jingsun JIANG ; Qiongying ZHANG ; Qinghua TAN ; Hui GONG ; Linjie GUO ; Chuanhui LI ; Jiang DU ; Huan TONG ; Bing HU ; Jie SONG ; Chengwei TANG ; Jing LI ; Ling LIU
Chinese Journal of Digestion 2020;40(11):745-750
Objective:To develop an diagnostic equipment with artificial intelligence (AI) real-time assistance under endoscopy (endoscopic AI equipment) for the detection of gastrointestinal protruding lesions, and to evaluate its performance and safety.Methods:From January to December 2017, at Endoscopy Center of West China Hospital, Sichuan University, the endoscopic images of individuals who underwent routine gastroscopy and colonoscopy were collected. The model was established based on convolutional neural network and the endoscopic AI equipment was developed. From June to December 2019, a prospective, single center, blinded and parallel controlled study was conducted to compare the differences in evaluation of protruding lesions of the same patient under gastroscopy or colonoscopy between endoscopist and the endoscopic AI equipment and to evaluated the impact of lesion size (lesions <5 mm and ≥5 mm) on the detection of endoscopic AI equipment. The main outcome measure was the detection time difference in reporting the protruding lesion between endoscopic AI equipment and endoscopist; and the secondary indicator was the accuracy of endoscopic AI equipment in detecting the protruding lesion. Wilcoxon rank sum test and chi-square test were used for statistical analysis.Results:A total of 71 582 white light endoscopy images were used for endoscopic AI equipment training, which included 41 376 images of protruding lesions. The endoscopic AI equipment was successfully developed and obtained the registration certificate of medical devices of the People′s Republic of China (Sichuan Instrument Standard, 20202060049). The accuracy, sensitivity, and specificity of endoscopic AI equipment in detecting protruding lesions were 96.4%, 95.1% and 92.8%, respectively. The detection time of each protruding lesions under gastroscopy of endoscopic AI equipment was 1.524 seconds faster than that of endoscopist; but the detection time of each protruding lesions under colonoscopy was 0.070 seconds slower than that of endoscopist, and the differences were statistically significant ( Z=-5.505 and -4.394, both P<0.01). The detection time of each protruding lesions under gastroscopy or colonoscopy of endoscopic AI equipment was not inferior to that of endoscopist. The detection rate of protruding lesions under colonoscopy by endoscopic AI equipment was 89.9% (249/277) and the sensitivity was 89.9%; the detection rate of protruding lesions under colonoscopy was 87.0% (450/517) and the sensitivity was 86.9%. There were no statistically significant differences in the detection time difference, sensitivity and missed diagnostic rate between the lesions <5 mm and ≥5 mm detected by endoscopic AI equipment under gastroscopy (all P>0.05). The sensitivity of endoscopic AI equipment in detecting the lesions ≥5 mm under colonoscopy was higher than that of lesions <5 mm (96.8% vs. 84.9%), and the missed diagnostic rate was lower than that of lesions <5 mm (3.2%, 3/94 vs. 15.1%, 61/405), and the differences were statistically significant ( χ2=9.615 and 9.612, both P=0.002). No adverse events on patients and medical staffs occurred, and there were no cases of equipment electricity leakage, and abnormal work reported during the use of endoscopic AI equipment. Conclusions:The endoscopic AI equipment can report the protruding lesions simultaneously with endoscopists, and the accuracy is close to 90%, which is expected to be a practical assistant for endoscopists to avoid missed detection of protruding lesions.
7.Application and evaluation of diversified teaching mode in clinical teaching for medical students
Ran LI ; An SONG ; Linjie WANG ; Lian DUAN ; Huijuan ZHU ; Mei LI ; Weibo XIA
Basic & Clinical Medicine 2024;44(4):577-581
Objective To investigate the needs and feedback from clinical medical students on the diversified teaching mode adopted by the Department of Endocrinology in Peking Union Medical College Hospital.Methods Questionnaires were distributed to the medicine students who were in clinical rotation in Peking Union Medical Col-lege,and the teaching status and teaching effect was investigated.Results A total of 95 valid questionnaires were received.The attending physicians and the teaching resident physicians performed well in the daily teaching activi-ties.The medical students believed that outpatient training was necessary in addition to ward rotations.After the ro-tation in the endocrinology department,the self-evaluated score of mastery of endocrinology knowledge had been significantly improved,especially in those who rotated in outpatient clinic,suggesting that outpatient teaching was of great significance.In addition,the establishment of a self-learning platform including clinical cases and videos in endocrinology could be used as an important supplementary means for clinical teaching.Conclusions Outpatient training improves learning outcomes of medical students,so must be kept and further strengthened in the future.Building a database of typical clinical cases and teaching videos can improve the training quality.