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.Effects of Lux? 1 540 nm non-ablative fractional laser combined with compound betamethasone on coarse pores
Xuguang LEI ; Yongyu ZHANG ; Xiaojin MIAO ; Yan DONG ; Xiaohui SIU ; Xingxing CHEN ; Bingyang YU
Chinese Journal of Medical Aesthetics and Cosmetology 2020;26(3):228-230
Objective:To explore the application of Lux? 1540 nm non-ablative fractional laser in the coarse pores.Methods:A total of 100 patients were treated with Lux? 1540 nm non-ablative fractional laser once a month for rough facial skin and thick pores, with a total of 4 times of treatment. Subjective evaluation and photo evaluation were used to evaluate the therapeutic effect one month after treatment.Results:The facial skin roughness and pore roughness improved after treatment, and the differences were statistically significant ( t=21.345, P<0.05). After treatment, 80 patients were much satisfied, 17 were satisfied, and 3 were dissatisfied, with a satisfactory rate of 97%. Conclusions:Lux? 1 540 nm non-ablative fractional laser has a positive therapeutic effect on rough skin and thick pores, with high safety and few side effects.
4.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.
5.Efficacy and safety of direct-acting antiviral agent regimens in a real-world cohort of adult Chinese patients with chronic hepatitis C virus infection
Wei JINYUAN ; Mei YONGYU ; Li JIANPING ; Yuan JING ; Yang XIAOHUA ; Xu ZHEN ; Lin GUOLI ; Zhang JUAN ; Zhao ZHIXIN ; Zhang XIAOHONG
Liver Research 2020;4(2):101-107
Background and aims:To investigate the safety and efficacy of direct-acting antiviral(DAA)regimens in a cohort of Chinese patients with chronic hepatitis C virus(HCV)infection. Methods:A total of 222 adult Chinese patients were enrolled and treated via DAA regimens in accor-dance with HCV management guidelines.Treatment responses were evaluated 4 weeks after treatment,at the end of treatment(EOT)and 12 weeks post-treatment.Virological responses,biochemical re-sponses,model for end-stage liver disease(MELD)and Child-Pugh(CP)scores were recorded. Results:A total of 218 patients(98.2%)achieved sustained virological response 12 weeks post-treatment and 4 patients relapsed.The combined number of rapid virological responses for all six regimens was 170/222(76.6%),and 221/222(99.6%)had achieved virological responses by the end of treatment.In decompensated cirrhosis patients the baseline mean CP score was 6.8±1.3 and the mean MELD score was 10.1±3.3.Compared with the mean CP score at baseline,the mean score is significantly lower at the end of treatment(5.7±1.3)and 12 weeks post-treatment(5.6±1.0).Estimated glomerular filtration rates did not differ significantly from baseline during the treatment or 12 weeks post-treatment.The incidence of adverse events in patients with chronic hepatitis C and compensated cirrhosis was 42/172(24.4%),and in patients with decompensated cirrhosis it was 8/22(36.4%).The most frequently reported adverse events were elevated indirect bilirubin,fatigue and rash.There were no cases of serious adverse events,death or treatment discontinuation because of adverse events. Conclusion:DAA regimens were highly effective and well tolerated irrespective of HCV genotype,cirrhosis,liver or kidney transplantation,hepatocellular carcinoma,HCV/hepatitis B virus co-infection,or renal failure.
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 effects and safety of Lux 1540 nm non-stripping array laser in treatment of facial skin rejuve-nation
Yongyu ZHANG ; Xuguang LEI ; Xiaojin MIAO ; Yan DONG ; Xiaohui SUI ; Xingxing CHEN ; Bingyang YU
Chinese Journal of Medical Aesthetics and Cosmetology 2019;25(3):231-233
Objective To explore the application of Lux1540 nm non-stripping array laser in fa-cial rejuvenation .Methods A total of 100 patients were collected for Lux1540 nm non stripped lattice laser treatment in patients with facial skin aging ,once a month ,totally four times treatment ;1 month after the treatment ,the skin of patients was analyzed by skin image analyzer VISIA for quantitative e-valuation .Results After 4 treatments ,the skin wrinkles ,texture ,pores ,skin roughness ,brown spots ,erythrocyte and purple spots were all improved ,with statistically significant differences (P <0 .05) ,while the changes of ultraviolet spots were not obvious ,and the differences were not statistical-ly significant (P > 0 .05) .After treatment ,80 patients were satisfied ,17 were comparatively satisfied , and 3 were dissatisfied ,with a satisfactory rate of 97% .All patients had needle-like pain during the treatment ,which could be tolerated without local anesthesia ointment .Ice compress was given after treatment ,which significantly alleviated the discomfort after treatment .Only 3 cases had mild pig-mentation .During the treatment and follow-up ,no adverse events such as skin redness and swelling , pigmentation and pruritus were found .Conclusions Lux1540 nm non-ablative dot array laser has posi-tive efficacy ,high safety and few side effects in facial rejuvenation ,and it is an effective method to treat facial skin aging .
8. Safety and efficacy of DCV-based DAAs therapy for chronic HCV infection in China
Jinyuan WEI ; Dengna LIN ; Zhebin WU ; Jianyun ZHU ; Zhixin ZHAO ; Yongyu MEI ; Chaoshuang LIN ; Juan ZHANG ; Xiaohong ZHANG
Chinese Journal of Hepatology 2018;26(12):933-939
Objective:
To evaluate the efficacy and safety of DCV-based DAAs therapy for chronic HCV infected Chinese patients.
Methods:
An open-label, non-randomized, prospective study was designed. Fifty-two patients with chronic HCV infection were enrolled. Among them, there was one patient after liver transplantation, 2 patients after kidney transplantation, 3 patients with hepatocellular carcinoma, and 4 patients with HBV infection. Thirteen cases with chronic hepatitis C (one compensated cirrhosis) who were negative for resistance-related variants [NS5A RAS (-)] of gene 1b and NS5A were treated with daclatasvir (DCV) + asunaprevir (ASV) for 24 weeks. Twenty-five cases of CHC (six compensated cirrhosis) with GT 1b, 2a, 3a, 3b, 6a were treated with DCV + SOF ± RBV for 24 weeks. 8 cases with decompensated cirrhosis of gene 1b and NS5A RAS(-) were given DCV + SOF + RBV regimen for 12 weeks. Six cases with decompensated cirrhosis, of gene 2a, 1b, 2a, 3a, 3b, were given DCV + SOF + RBV regimen for 24 weeks. HCV RNA, blood routine test, liver and kidney function, and upper abdominal ultrasound/MRI were measured at baseline, 4 weeks of treatment, end of treatment, and 12 weeks of follow-up. The incidence of adverse events and laboratory abnormalities during treatment were recorded. A t-test was used to compare the measurement data between two groups, and analysis of variance was used to compare the measurement data between multiple groups.
Results:
Sixteen patients (100%) achieved SVR12 after treatment, with 0% recurrence rate. Rapid virological response (RVR) of the four treatment regimens were 76.92%, 54.17%, 87.50%, and 83.33%, respectively, and 32 patients achieved 100% virological response after the completion of treatment. The incidence of adverse events of chronic hepatitis C with cirrhosis and decompensated cirrhosis was 62.5% and 64.29%, respectively. The most common adverse event was fatigue in CHC (25.00%), and elevated indirect bilirubin in decompensated cirrhosis (42.86%). No serious adverse drug events, deaths or adverse reactions occurred.
Conclusion
DCV-based DAAs regimen is promising option for the treatment of HCV genotypes, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and HCV infection after liver/kidney transplantation in china. Above all, it has high SVR12 with good tolerability and safety profile.
9.Effects of cannabinoid HU210 on experimental acute pancreatitis and possible relationship with Toll-like receptor 4 signaling pathway
Ruiqin ZHANG ; Sisi LIN ; Min LI ; Li SHEN ; Kun LI ; Yongyu LI
Chinese Journal of Pathophysiology 2017;33(6):1112-1118
AIM:Using Toll-like receptor 4 gene knockout (tlr4-/-) mice and the wild-type (WT) mice with the same C57BL/10J genetic background, the effects of HU210, a cannabis preparation, on caerulein (CAE)-induced acute pancreatitis (AP) and the potential mechanisms were investigated.METHODS:WT or tlr4-/-mice were randomly divided into AP group, AP+HU210 group and control group.AP was induced by intraperitoneal injection of CAE (50 μg·kg-1·h-1) for a total of 6 times and lipopolysaccharide (LPS) at 10 mg/kg 6 h after the first injection of CAE.HU210 (50 μg/kg) was given 30 min before and 4 h after the first injection of CAE in AP+HU210 group.The animals in control group were given normal saline instead of CAE and LPS in the same way.The mice were sacrificed 3 h after the last injection.The blood, the pancreas, the lungs and the intestinal Peyer's patches were harvested.RESULTS:Compared with control group, the pancreatic pathological score and P38 protein expression, plasma amylase activity and inflammatory mediator levels, and lung MPO activity were significant increased (P<0.05) in both WT and tlr4-/-mice with AP.Compared with the WT mice with AP, the tlr4-/-mice with AP showed significantly low levels of IL-6, TNF-α and MCP-1 in the plasma, low expression levels of pancreatic P38 and p-P38 protein (P<0.05), and mild alterations of CD3+ T-lymphocytes, CD4+ T-lymphocytes and the ratio of CD4+/CD8+ (P<0.05).The administration of HU210 attenuated the pancreatic pathological changes and the lung MPO activity in both stains of mice with AP (P<0.05).However, the inhi-bitory effects of HU210 on the increased amylase activity in the plasma and the increased protein levels of pancreatic P38 and p-P38 were remarkable (P<0.05) in WT mice instead of in tlr4-/-mice.CONCLUSION:TLR4 is mainly involved in AP-related systemic inflammatory response and its mechanism may be dependent on TLR4-P38 MAPK signaling pathway.The intervention of HU210 in AP plays a protective role mainly by inhibiting the infiltration of inflammatory cells, and the relationship with TLR4 signaling pathway is not obvious.
10.Targeted nano-vector for gene delivery into human bone marrow mesenchymal stem cells and cellular MR imaging in vitro
Pengfei PANG ; Bing LI ; Junjie MAO ; Bin ZHOU ; Xiaojun HU ; Yongyu ZHANG ; Feng AO ; Hong SHAN
Chinese Journal of Medical Imaging Technology 2017;33(10):1463-1469
Objective To explore the feasibility and efficacy of an MRI-visible,targeted,nano-vector which is synthesized by attaching a targeting ligand,the GD2 single chain antibody (scAb GD2),to the distal ends of PEG-g-PEI-SPION as a carrier for gene delivery into human bone marrow mesenchymal stem cells (hBMSCs) and in vitro cellular MR imaging.Methods scAbGD2-PEG-g-PEI-SPION was synthesized as previously reported.Gel electrophoresis was performed to assess the pDNA condensation ability of scAbGD2-PEG-g-PEI-SPION.The particle size and Zeta potential of scAbGD2-PEG-g-PEI-SPION/pDNA nanocomplexes were observed by dynamic light scattering.Cytotoxicity of scAbGD2-PEG-g-PEI-SPI-ON was evaluated by CCK-8 assay using hBMSCs.Gene transfection efficiency of scAbGD2-PEG-g-PEI-SPION in hBMSCs was quantified by flow cytometry,PEG-g-PEI-SPION,scAbGD2-PEG-g-PEI-SPION,scAbGD2-PEG-g-PEI-SPION+ free AbGD2 and scAbIgG2a-PEG-g-PEI-SPION group was established.The cellular internalization of scAbGD2-PEG-g-PEI-SPION/pDNA nanocomplexes was observed by confocal laser scanning microscopy and Prussian blue staining.MRI of scAbGD2-PEG-g-PEI-SPION was performed by cellular MRI scanning in vitro.Results scAbGD2-PEG-g-PEI-SPION condensed pDNA to form stable nanocomplexes of 80-100 nm in diameter and showed low cytotoxicity to hBMSCs.At the same N/P ratio,the transfection efficiency of scAbGD2-PEG-g-PEI-SPION group was significantly higher than those of other groups (P<0.001).At the optimal N/P ratio of 20,scAbGD2-PEG-g-PEI-SPION/pDNA obtained the highest transfection efficiency of (59.60 ± 4.50) % in hBMSCs.Furthermore,hBMSCs labeled with scAbGD2-PEG-g-PEI-SPION showed sensitive low signal intensity on MRI T2/T2 *-weighted images in vitro.Conclusion scAbGD2-PEG-g-PEI-SPION is an efficient MRL visible targeted nano vector for gene delivery into hBMSCs.

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