1.Upregulating KLF11 ameliorates intestinal inflammation in mice with 2, 4, 6-trinitrobenesulfonic acid-induced colitis by inhibiting the JAK2/STAT3 signaling pathway
Jin XI ; Min ZHANG ; Yongyu ZHANG ; Chen ZHANG ; Yulu ZHANG ; Rui WANG ; Lin SHEN ; Jing LI ; Xue SONG
Journal of Southern Medical University 2024;44(4):765-772
Objective To investigate the expression level of Kruppel-like transcription factor family member KLF11 in intestinal mucosal tissues of Crohn's disease (CD) and its regulatory effect on intestinal inflammation in CD-like colitis. Methods We examined KLF11 expression levels in diseased and normal colon mucosal tissues from 12 CD patients and 12 patients with colorectal cancer using immunofluorescence staining. KLF11 expression was also detected in the colon mucosal tissues of a mouse model of 2,4,6-trinitrobenesulfonic acid (TNBS)-induced colitis. A recombinant adenoviral vector was used to upregulate KLF11 expression in the mouse models and the changes in intestinal inflammation was observed. A Caco-2 cell model with stable KLF11 overexpression was constructed by lentiviral infection. The effect of KLF11 overexpression on expressions of JAK2/STAT3 signaling pathway proteins was investigated using immunoblotting in both the mouse and cell models. The mouse models were treated with coumermycin A1, a JAK2/STAT3 signaling pathway agonist, and the changes in intestinal inflammatory responses were observed. Results The expression level of KLF11 was significantly lowered in both the clinical specimens of diseased colon mucosal tissues and the colon tissues of mice with TNBS-induced colitis (P<0.05). Adenovirus-mediated upregulation of KLF11 significantly improved intestinal inflammation and reduced the expression levels of inflammatory factors in the intestinal mucosa of the colitis mouse models (P<0.05). Overexpression of KLF11 significantly inhibited the expression levels of p-JAK2 and p-STAT3 in intestinal mucosal tissues of the mouse models and in Caco-2 cells (P<0.05). Treatment with coumermycin A1 obviously inhibited the effect of KLF11 upregulation for improving colitis and significantly increased the expression levels of inflammatory factors in the intestinal mucosa of the mouse models (P<0.05). Conclusion KLF11 is downregulated in the intestinal mucosa in CD, and upregulation of KLF11 can improve intestinal inflammation and reduce the production of inflammatory factors probably by inhibiting the JAK2/STAT3 signaling pathway.
2.Upregulating KLF11 ameliorates intestinal inflammation in mice with 2, 4, 6-trinitrobenesulfonic acid-induced colitis by inhibiting the JAK2/STAT3 signaling pathway
Jin XI ; Min ZHANG ; Yongyu ZHANG ; Chen ZHANG ; Yulu ZHANG ; Rui WANG ; Lin SHEN ; Jing LI ; Xue SONG
Journal of Southern Medical University 2024;44(4):765-772
Objective To investigate the expression level of Kruppel-like transcription factor family member KLF11 in intestinal mucosal tissues of Crohn's disease (CD) and its regulatory effect on intestinal inflammation in CD-like colitis. Methods We examined KLF11 expression levels in diseased and normal colon mucosal tissues from 12 CD patients and 12 patients with colorectal cancer using immunofluorescence staining. KLF11 expression was also detected in the colon mucosal tissues of a mouse model of 2,4,6-trinitrobenesulfonic acid (TNBS)-induced colitis. A recombinant adenoviral vector was used to upregulate KLF11 expression in the mouse models and the changes in intestinal inflammation was observed. A Caco-2 cell model with stable KLF11 overexpression was constructed by lentiviral infection. The effect of KLF11 overexpression on expressions of JAK2/STAT3 signaling pathway proteins was investigated using immunoblotting in both the mouse and cell models. The mouse models were treated with coumermycin A1, a JAK2/STAT3 signaling pathway agonist, and the changes in intestinal inflammatory responses were observed. Results The expression level of KLF11 was significantly lowered in both the clinical specimens of diseased colon mucosal tissues and the colon tissues of mice with TNBS-induced colitis (P<0.05). Adenovirus-mediated upregulation of KLF11 significantly improved intestinal inflammation and reduced the expression levels of inflammatory factors in the intestinal mucosa of the colitis mouse models (P<0.05). Overexpression of KLF11 significantly inhibited the expression levels of p-JAK2 and p-STAT3 in intestinal mucosal tissues of the mouse models and in Caco-2 cells (P<0.05). Treatment with coumermycin A1 obviously inhibited the effect of KLF11 upregulation for improving colitis and significantly increased the expression levels of inflammatory factors in the intestinal mucosa of the mouse models (P<0.05). Conclusion KLF11 is downregulated in the intestinal mucosa in CD, and upregulation of KLF11 can improve intestinal inflammation and reduce the production of inflammatory factors probably by inhibiting the JAK2/STAT3 signaling pathway.
3.Effect of serum heat inactivation on the detection of 2019-nCoV antibodies
Yuhai HU ; Xiumei HU ; Taixue AN ; Peifu TIAN ; Qiang LI ; Xiaodan ZHENG ; Jing WANG ; Bo SITU ; Dehua SUN ; Yongyu RUI ; Qian WANG ; Lei ZHENG
Chinese Journal of Experimental and Clinical Virology 2021;35(6):719-722
Objective:To assess the effect of serum heat inactivation on the detection of 2019 novel coronavirus (2019-nCoV) specific IgM and IgG antibodies by colloidal gold method.Methods:The serum specimens were collected from a total of 106 Coronavirus Disease 2019 (COVID-19) patients and 52 control subjects. Both the fresh serum and the heat inactivated serum samples from the same patient were detected simultaneously with the 2019-nCoV IgM and IgG antibodies detection kit (colloidal gold method). According to the patient′s onset time, the positive rates of antibodies production profile were calculated. The influence of heat inactivation on the detection rates of antibodies at different stages of disease after onset was analyzed.Results:The test results of the specimens of the healthy control group before and after inactivation were all negative. For the 106 specimens of COVID-19 patients, the detection rates of 2019-nCoV specific IgM and IgG antibodies were reduced after heating at 56 ℃ for 30 min. The positive rates of IgM antibodies significantly decreased from 66.04% (70/106) to 43.40% (46/106) ( χ2=22.042, P=0.000), while the positive rates of IgG antibodies slightly decreased from 81.13% (86/106) to 76.42% (81/106) ( χ2=0.800, P=0.063). Further analysis revealed that there was a significant difference in the positive rates of IgM antibodies before and after heat inactivation in the 3rd, 5th and 6th week after onset. However, there was no statistically significant difference in the detection rates of IgG antibodies before and after serum heat inactivation in different periods of onset. Conclusions:Heat inactivation significantly decreased the detection rates of 2019-nCoV specific IgM antibodies, which may lead to serological false negative results.
4.Identification and antibiotics sensitivity analysis of Herbaspirillum huttiense in catheter-related bloodstream infection
Xiumei HU ; Biao YANG ; Li LIN ; Hengrui ZHAO ; Jing CHEN ; Fang ZHOU ; Bing SU ; Yongyu RUI ; Qian WANG ; Lei ZHENG
Chinese Journal of Laboratory Medicine 2020;43(5):582-586
Objective:To analyze the identification and antibiotics susceptibility of Herbaspirillum in catheter-related bloodstream infection, and improve the awareness and attention of the rare pathogenic microorganisms for clinicians and microbiologists. Methods:The bacterium was isolated from a positive blood culture of a hemodialysis patient with chronic renal failure. The smear of isolate was prepared, stained and observed by microscope. The single colonies were identified by mass spectrometry and VITEK 2 Compact identification and antibiotics sensitivity analysis system, respectively. Then, 16S ribosomal DNA (rDNA) was amplified and sequenced, and bacterial genome was sequenced.Results:The gram-negative bacilli was found in the positive blood culture bottle. After incubated on blood agar for 16 hours, milky white, bulging and non-haemolytic colonies were observed. The identification result was Burkholderia cepacian by VITEK 2_Compact and antimicrobial susceptibility testing showed resistance to aztreonam and polymyxin but sensitive to other drugs in N335 card. The isolate could not be identified by VITEK MS with clinical database. However, it was identified as Herbaspirillum huttiense/Herbaspirillum aquaticum with research database. The 16S rDNA of the strain was consistent with Herbaspirillum huttiense and Herbaspirillum aquaticum (more than 99%). High-throughput bacterial genome sequencing revealed that the isolate in this case shared 100% homology with Herbaspirillum huttiense subsp putei IAM 15032 in Genbank database, which confirmed that the isolate was Herbaspirillum huttiense. Conclusions:There are more and more environmental microorganisms evolved into human pathogenic bacteria. Herbaspirillum species are easy to be misidentified because its biochemical characteristics are similar to other strains.
5.Epidemiological characteristic and current status of surgical treatment for esophageal cancer by analysis of national registry database
Yousheng MAO ; Shugeng GAO ; Qun WANG ; Xiaotian SHI ; Yin LI ; Wenjun GAO ; Fushun GUAN ; Xiaofei LI ; Yongtao HAN ; Yongyu LIU ; Junfeng LIU ; Kang ZHANG ; Shuoyan LIU ; Xiangning FU ; Wentao FANG ; Longqi CHEN ; Qingchen WU ; Gaoming XIAO ; Keneng CHEN ; Guanggen JIAO ; Shijiang ZHANG ; Weimin MAO ; Tiehua RONG ; Jianhua FU ; Lijie TAN ; Chun CHEN ; Shidong XU ; Shiping GUO ; Zhentao YU ; Jian HU ; Zhendong HU ; Yikun YANG ; Ningning DING ; Ding YANG ; Jie HE
Chinese Journal of Oncology 2020;42(3):228-233
Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.
6.Epidemiological characteristic and current status of surgical treatment for esophageal cancer by analysis of national registry database
Yousheng MAO ; Shugeng GAO ; Qun WANG ; Xiaotian SHI ; Yin LI ; Wenjun GAO ; Fushun GUAN ; Xiaofei LI ; Yongtao HAN ; Yongyu LIU ; Junfeng LIU ; Kang ZHANG ; Shuoyan LIU ; Xiangning FU ; Wentao FANG ; Longqi CHEN ; Qingchen WU ; Gaoming XIAO ; Keneng CHEN ; Guanggen JIAO ; Shijiang ZHANG ; Weimin MAO ; Tiehua RONG ; Jianhua FU ; Lijie TAN ; Chun CHEN ; Shidong XU ; Shiping GUO ; Zhentao YU ; Jian HU ; Zhendong HU ; Yikun YANG ; Ningning DING ; Ding YANG ; Jie HE
Chinese Journal of Oncology 2020;42(3):228-233
Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.
7.Clinical evaluation of artificial intelligence system based on fundus photograph in diabetic retinopathy screening
Meng LI ; Gengyuan WANG ; Honghui XIA ; Xiaoying TANG ; Ziqing FENG ; Yongyu YAO ; Yijin HUANG ; Wei FAN ; Zhe YUAN ; Jin YUAN
Chinese Journal of Experimental Ophthalmology 2019;37(8):663-668
Objective To study the efficiency and accuracy of artificial intelligence (AI) system based on fundus photograph in diabetic retinopathy(DR)screening,and evaluate the clinical application value of AI system. Methods A diagnostic trial was adopted. Total of 13683 color fundus photos were collected in Zhaoqing Gaoyao People's Hospital from March,2017 to November,2018. The AI system for DR (ZOC-DR-V1) was established,based on transfer learning + NASNet algorithm,by training 4465 precisely labeled fundus images (2510 normal,and 1955 with any stage of DR). One thousand confirmed fundus images (300 normal and 700 with any stage of DR),diagnosed by AI ( AI group ) and doctors ( 3 ophthalmologist doctors and 3 endocrinologist doctors ) ( doctor group ) , respectively. Ophthalmologist group and endocrinologist group were both composed of primary,intermediate and senior physicians. The mean reading time of each image and the total time of 1000 images were recorded. The accuracy and efficiency of AI system and doctor groups were compared. The reading process was divided into two stages. The diagnostic coincidence rate and the average reading time of each group between the two parts were calculated and compared. This study protocol was approved by Ethic Committee of Zhongshan Ophthalmic Center, Sun Yat-sen University (No. 2017KYPJ104). Results After training,the diagnostic coincidence rate of AI system (ZOC-DR-V1) in test set was 94. 7%,AUC was 0. 994. In this "man-machine to war",the diagnostic coincidence rate of primary,intermediate and senior endocrinologist was 94. 0%,91. 4% and 93. 4%;the diagnostic coincidence rate of primary,intermediate and senior ophthalmologist was 92. 7%,94. 4% and 95. 6%;the diagnostic coincidence rate of AI system was 95. 2%. There was no difference in the diagnostic coincidence rate between AI system and senior ophthalmologist ( P = 0. 749 ) . The mean reading time of each image of primary, intermediate and senior endocrinologists was (4. 63±1. 87),(3. 74±3. 47) and (5. 71±3. 47) seconds,and the total time of 1000 images of primary,intermediate and senior endocrinologists was 1. 29,1. 04 and 1. 58 hours;the mean reading time of each image of primary,intermediate and senior ophthalmologists was ( 7. 25 ± 6. 58 ) , ( 5. 18 ± 5. 01 ) and ( 5. 18 ± 3. 47 ) seconds,and the total time of 1000 images of primary,intermediate and senior endocrinologists was 2. 02,1. 44 and 1. 44 hours;the mean and total time of AI system was (1. 62±0. 67) seconds and 0. 45 hours,and the reading time of AI system was significantly shorter than that of the doctor groups (all at P=0. 000). The diagnostic coincidence rates between previous and posterior part of primary endocrinologist, primary and intermediate ophthalmologist were significantly different (χ2=11. 986,6. 517,10. 896;all at P<0. 05),and the mean reading time in the posterior part was significantly shorter than that in the previous part of intermediate and senior endocrinologist and primary ophthalmologist (t=4. 175,8. 189,5. 160;all at P<0. 01). While the reading time of AI system remained stable throughout the process(χ2=3. 151,P=0. 103;t=0. 038,P=0. 970). Conclusions The ophthalmic AI system based on fundus images has a good diagnostic efficiency,and its diagnostic coincidence rate can compare with senior ophthalmologist,providing a new method and platform for large-scale DR screening.
8. Effects of resolvin D1 on the autophagy in acute pancreatitis in mice
Bingbing WANG ; Cui HU ; Xiaochang LIU ; Junjun BAO ; Jingjing YUAN ; Yongyu MEI ; Qiao MEI ; Jianming XU
Chinese Journal of Digestion 2018;38(6):400-404
Objective:
To investigate the effects of resolvin D1 on autophagy in the prevention of acute pancreatitis (AP) in mice.
Methods:
Thirty C57BL/6 mice were divided into control group, AP group and resolvin D1 group. AP model was established by intraperitoneal injection of cerulein at 50 μg·kg-1·h-1. Resolvin D1 was intraperitoneally given at 50 μg/kg one hour before and four hours after modeling. The mice of control group were intraperitoneally injected the same volume of 0.9% sodium chloride solution. The serum levels of amylase and lipase were measured by colorimetric method. The pathological injury of the lung and pancreatitis were observed under optical microscope. Autophagic vacuoles in acinar cells of pancreas of mice were evaluated by transmission electron microscope. And the expressions of autophagy related markers Beclin-1, p62 and LC3-Ⅱ at the mRNA and protein levels in pancreas of mice were detected by real time quantitative polymerase chain reaction (RT-qPCR) and Western blotting method. One-way analysis of variance and SNK-
9.Research on Tissue Metabolomics of 29 Patients with Hepatocellular Carcinoma
Jun LI ; Shujun SUN ; Yang WANG ; Caifeng LIU ; Xingyang ZHONG ; Feng XU ; Zhigang CAI ; Yongyu ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(4):578-586
The present study aimed to research pathogenesis and therapeutics of hepatocellular carcinoma (HCC) with the method of tissue metabolomics.A combined gas chromatography-mass spectrometry (GC-MS) method was developed suitable for analyzing the endogenous small molecule of liver cancer tissues and adjacent tissues.The unidimensional and multidimensional statistics were used to look for differential metabolites.And then,the KEGG and HMDB database were utilized to find related differential pathways and pathogenesis of HCC.The PCA and PLS-DA showed that there were significant differences on the endogenous small molecule of liver cancer tissues and adjacent tissues.Through the OPLS-Loading plot analysis,there were 25 differential metabolites and 36 relevant pathways.The differential pathways belong to carbohydrate metabolism,amino acid metabolism and mitochondrial transfer.There were 16 metabolites' area under the ROC curve which was bigger than 0.8,which were related with ATP-binding cassette (ABC) transporters,galactose metabolism,amino sugar and nucleotide sugar metabolism.It was concluded that the Warburg effect exists in HCC cells.The energy of HCC cell was from glycolytic function,because the glycolysis was enhanced and the citric acid cycle decreased.Mitochondrial dysfunction and the increased cobalt content may correlate with the Warburg effect,which may be one of the pathogenesis of liver cancer,and expected to become the breakthrough point of a new targeting therapeutic approach.
10.Precision Application of Metabolomics Technology in Brain Diseases
Junwei FANG ; Zhigang CAI ; Shujun SUN ; Yang WANG ; Yongyu ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(9):1549-1554
As the most downstream of biology information current,metabolism has the special function of information delivery.Work principle and disease mechanism of brain can be better reflected based on the combination of metabolism and gene,transcription,protein and nervous system.At present,there are many reports regarding metabolomics research in the brain to explore the diseases' effect on brain metabolism.Combined with precision medicine,precision application of metabolomics technology in brain diseases was reviewed in this paper.

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