1.Effect of gadolinium chloride pretreatment on experimental hepatocarcinogenesis of H_(22) cells in mice
Mengyuan WANG ; Xiong DING ; Jianping GONG
Journal of Third Military Medical University 1988;0(05):-
Objective To investigate the effect of gadolinium chloride (GdCl3) on the H22 experimental hepatocarcinogenesis in mice. Methods Totally 80 mice were inflicted to experimental hepatoma by implanting H22 cells to their liver lobes, and then equally and randomly divided into experimental hepatoma group (B) and GdCl3 pretreatment group (10 mg/kg, C). Another 40 mice served as normal control group (A). Ten mice from every group were killed respectively 7, 14, and 28 d after implantation. The left 10 mice were used for recording survival time and measuring the mass weight. Hepatic pathological histology was observed, and the expression of TNF-? was detected by ELISA and RT-PCR. Results ①Survival time was obviously higher in group B than in group C (P
2.Immunoglobulin-like domain-containing receptor 2 deficiency aggravates ischemia- reperfusion-induced renal fibrosis
Mengyuan XU ; Xin WANG ; Yongfeng GONG
Chinese Journal of Nephrology 2023;39(4):281-290
Objective:To investigate the role of immunoglobulin-like domain-containing receptor 2 (Ildr2) in renal fibrosis induced by ischemia-reperfusion.Methods:Ildr2 knockout mice (KO group) were constructed using CRISPR/Cas9 technology, and wild-type mice were as the control group (WT group). The unilateral renal ischemia-reperfusion (UIR) model (UIR group) was constructed by clamping the left renal pedicle, and was divided into KO-UIR group and WT-UIR group after modeling. Sham operation mice (sham group) were not treated with ischemia. Serum creatinine was measured by creatinine oxidase method. Blood urea nitrogen was detected by the diacetyloxime colorimetric method. The urinary albumin level was measured by enzyme-linked immunosorbent assay, and urinary albumin/creatinine ratio was calculated. HE, PAS and MASSON staining were used to detect the infiltration of inflammatory cells and the degree of fibrosis in renal tissues. The mRNA expression levels of Ildr2, kidney injury-associated molecules neutrophil gelatinase-associated lipocalin ( NGAL) and kidney injury molecule-1 ( KIM-1), fibrosis markers typeⅠcollagen α 1 ( Col1α1), fibronectin 1 ( Fn1), α-smooth muscle actin ( α-SMA) and connective tissue growth factor ( CTGF), as well as inflammation-related molecules macrophage marker F4/80 and monocyte chemoattractant protein-1 ( MCP-1) were detected by real time quantitative PCR (qRT-PCR). The protein levels of Ildr2, α-SMA and Col1α1 were detected by immunofluorescence and Western blotting. Results:(1) qRT-PCR and Western blotting showed that the expression levels of Ildr2 mRNA and protein in UIR group were significantly lower than those in sham group (both P<0.05). (2) There were no significant differences in body weight, serum creatinine, blood urea nitrogen, total cholesterol, low density lipoprotein, high density lipoprotein and triglyceride between KO group and WT group (all P>0.05). qRT-PCR results showed that there were no significant differences in the mRNA expression levels of NGAL, KIM-1, α-SMA, Col1α1, CTGF, Fn1, MCP-1 and F4/80 between KO group and WT group (all P>0.05). Histological staining showed no abnormal inflammatory cell infiltration and interstitial fibrosis between KO group and WT group. (3) Compared with the WT-UIR group, serum creatinine and blood urea nitrogen in the KO-UIR group were significantly higher (both P<0.05). qRT-PCR results showed that the mRNA expression levels of NGAL, F4/80, MCP-1, Col1α1, α-SMA, and CTGF in the KO-UIR group were significantly higher than those in the WT-UIR group (all P<0.05). Immunofluorescence and Western blotting results also showed that the protein expression levels of Col1α1 and α-SMA in the KO-UIR group were significantly higher than those in the WT-UIR group (all P<0.05). Histological staining showed that, compare with WT-UIR group, KO-UIR group had more severe inflammatory infiltration and more collagen fiber deposition. Conclusion:Ildr2 knockout does not cause phenotypic changes in mice under normal physiological conditions. Ildr2 plays a regulatory role in UIR injury, and Ildr2 deletion aggravates the degree of renal fibrosis induced by UIR.
3.The diagnostic performance of MR psychoradiology in identifying patients with mental disorders
Mengyuan XU ; Wenjing ZHANG ; Fei LI ; Youjin ZHAO ; Bo TAO ; Qiang YUE ; Jiahe XIAO ; Zhenlin LI ; Hehan TANG ; Su LYU ; Qiyong GONG
Chinese Journal of Radiology 2021;55(4):390-396
Objective:To explore the efficiency of MR psychoradiology examination in screening and classification of psychiatric disorders as well as its potential clinical application.Methods:Retrospective study was conducted for 144 patients with MR psychoradiology examination, who were diagnosed mental disorders based on International Statistical Classification of Diseases and Related Health Problems Tenth Revision (ICD-10) from September 2018 to July 2020 in West China Hospital of Sichuan University. As our previous studies, imaging diagnostic models were constructed based on gray matter volume (GMV) analysis for four kinds of psychiatric disorders, including depression, anxiety disorder, bipolar disorder and schizophrenia. For 120 patients with psychiatric disorders, the GMV change pattern of brain regions was detected and subtyped by MR psychoradiology examination with 50% similarity threshold of the above imaging diagnostic models. The diagnostic efficiency of MR psychoradiology examination was evaluated with references of clinical diagnose. For 24 patients with dementia, brain atrophy was additionally measured by conventional MR examination and MR psychoradiology examination respectively.Results:The sensitivity, specificity, Youden index and accuracy of MR psychoradiology in identifying the four psychiatric disorders were 86.6% (84/97), 69.6% (16/23), 0.56 and 83.3% (100/120), including depression [77.8% (28/36), 69.0% (58/84), 0.47, 71.7% (86/120)], schizophrenia [58.8% (10/17), 91.3% (94/103), 0.50, 86.7% (104/120)], bipolar disorder [42.1% (8/19), 96.0% (97/101), 0.38, 87.5% (105/120)] and anxiety disorder [24.0% (6/25), 100% (95/95), 0.24, 84.2% (101/120)]. As for 24 patients with dementia, 58.3% (14/24) were detected with brain atrophy by conventional MR examination, while 91.7% (22/24) were detected by MR psychoradiology examination.Conclusions:MR psychoradiology can detect the subtle brain structural abnormalities of patients with mental disorders. Although it can′t be used as an independent biomarker for disease diagnosis till now, it is of great help in improving the accuracy and objectivity of diagnosis.
4.Clinical characteristics analysis of acute pancreatitis
Qiqi WANG ; Yali CHENG ; Cancan ZHOU ; Mengyuan GONG ; Haonan LIU ; Zheng WANG ; Qingyong MA ; Zheng WU
Chinese Journal of Digestive Surgery 2023;22(S1):38-43
Objective:To analyze the clinical characteristics of acute pancreatitis.Methods:The retrospective case-control study was conducted. The clinical data of 558 patients with acute pancreatitis who were admitted to The First Affiliated Hospital of Xi′an Jiaotong University from June 2015 to June 2023 were collected. There were 352 males and 206 females, aged (46±15)years. Observation indicators: (1) general situations of acute pancreatitis patients; (2) etiology of acute pancreatitis patients; (3) severity of acute pancreatitis patients; (4) chronic diseases in acute pan-creatitis patients; (5) complications in acute pancreatitis patients; (6) subgroup analysis of patients with recurrent acute pancreatitis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the rank sum test. Bonferroni correction was used for pairwise comparison. Results:(1) General situations of acute pancreatitis patients. There were significant differences in gender, age, total duration of hospital stay, smoking, and alcohol consumption between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (2) Etiology of acute pancreatitis patients. There were significant differences in gallstones and hyperlipidemia between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (3) Severity of acute pancreatitis patients. Of the 443 patients with first episode of acute pancreatitis and 115 patients with recurrent acute pancreatitis, cases with mild acute pancreatitis, cases with moderate-severe acute pancreatitis, cases with severe acute pan-creatitis were 320 and 83, 24 and 9, 99 and 23, showing no significant difference between them ( P>0.05). (4) Chronic diseases in acute pancreatitis patients. There were significant differences in com-plication as hyperlipidemia, fatty liver and diabetes between the first episode of acute pancreatitis patients and the recurrent acute pancreatitis patients ( P<0.05). (5) Complications in acute pancrea-titis patients. There was no significant difference in terms of acute necrotic collection, acute peripan-creatic fluid accumulation, walled-off necrosis, pancreatic pseudocyst, infectious pancreatic necrosis, systemic inflammatory response syndrome, respiratory system complications, circulatory system complications, renal complications, sepsis, abdominal compartment syndrome, or pancreatic ence-phalopathy between the first episode of acute pancreatitis patients and the recurrent acute pancrea-titis patients ( P>0.05). (6) Subgroup analysis of patients with recurrent acute pancreatitis. ① Combination with chronic diseases. Of the 115 patients with recurrent acute pancreatitis, cases with mild acute pancreatitis, cases with moderate-severe acute pancreatitis, cases with severe acute pancreatitis were 83, 9, 23, and there were 25, 8, 11 cases of them with hyperlipidemia, respectively, showing a significant difference among them ( P<0.05). ② Complications. Of the 115 patients with recurrent acute pancreatitis, there were 44 cases with hyperlipidemia and 71 cases without hyper-lipidemia, and there were significant differences in acute peripancreatic fluid accumulation and renal complications between them ( P<0.05). Conclusions:Recurrent acute pancreatitis is more common in males. Compared with first episode of acute pancreatitis, cases with recurrent acute pancreatitis usually have younger age, shorter total duration of hospital stay, higher proportion of smoking and drinking. The etiology of recurrent acute pancreatitis is composed of lower levels of biliary diseases and higher levels of hyperlipidemia. Patients with recurrent acute pancreatitis have higher proportion of comorbidities as hyperlipidemia, fatty liver and diabetes. There was no signifi-cant difference in the incidence of complications between first episode of acute pancreatitis and recurrent acute pancreatitis. Compared with recurrent acute pancreatitis patients without concomi-tant hyperlipidemia, recurrent acute pancreatitis patients with concomitant hyperlipidemia are more prone to acute peripancreatic fluid accumulation and renal complications.
5.Bioinformatics analysis of survival-related genes in pancreatic cancer based on GEO and TCGA database
Mengyuan GONG ; Qiqi WANG ; Zeen ZHU ; Zheng WU ; Zheng WANG ; Weikun QIAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2023;44(5):717-724
【Objective】 Based on Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database, survival analysis was used to screen the key prognostic genes involved of pancreatic cancer patients. 【Methods】 Two pancreatic cancer gene chips (Microarray) from the GEO database and transcriptome sequencing (RNA-seq) from the TCGA database were used to filter the survival-related genes using Kaplan-Meier (KM) analysis and Cox risk model, and the target genes were intersected. Prognosis-associated genes were screened first and then pathway enrichment analysis or immune-enrichment analysis was performed based on these genes to find out their potential molecular mechanisms in regulating pancreatic cancer. 【Results】 In this study, five survival-related genes (i.e., CDO1, DCBLD2, FAM83A, ITGA3 and SLC16A3) were screened out. Multifactorial Cox regression analysis and clinical correlation analysis showed that high CDO1 expression was a protective factor for pancreatic cancer prognosis, and its antitumor effect was associated with its role in inhibiting the malignant biological behavior of pancreatic cancer cells and promoting the infiltration of immune killer cells in pancreatic cancer. 【Conclusion】 This study suggests that CDO1 is a potential tumor suppress gene of pancreatic cancer, and the tumor inhibition effect of CDO1 may be related to its role in remodeling the immune microenvironment of pancreatic cancer.
6.Huaier alleviates acute pancreatitis in mice by reducing ROS-induced pyroptosis in acinar cells
Mengyuan GONG ; Bo ZHANG ; Ze’en ZHU ; Qingyong MA ; Zheng WU ; Zheng WANG ; Weikun QIAN
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(2):183-191
【Objective】 To investigate the therapeutic effect of Huaier on acute pancreatitis (AP) and its potential mechanism. 【Methods】 A mouse model of cerulean-induced AP was used to verify the therapeutic effect of Huaier in vivo. HE staining and immunohistochemical staining were used to evaluate the histopathological changes of the pancreas, and transmission electron microscopy was used to observe the pyroptosis morphology of the pancreas. In vitro, 266-6 cell line was used as the experimental carrier to verify the protective effect of Huaier on acinar cells. Electron microscopy and Western blotting were used to evaluate the pyroptosis level of acinar cells, and ROS fluorescence probe was used to detect the oxidative stress state of acinar cells. 【Results】 Huaier significantly alleviated the severity of AP in mice. HE staining of pancreas showed that necrosis and inflammatory cell infiltration were reduced, and the level of serum amylase was decreased. Immunohistochemical staining and Western blotting showed that Huaier effectively inhibited the expressions of pyroptosis-related molecules such as NLRP3 and GSDMD in pancreatic tissue. Electron microscopy showed that Huaier could reduce the pyroptosis level of pancreatic acinar cells under inflammatory state. In addition, the level of ROS in acinar cells was significantly reduced after the intervention of Huaier, and ROS-mediated pyroptosis of acinar cells could be effectively inhibited by Huaier. 【Conclusion】 Huaier can effectively reduce the severity of AP by inhibiting ROS-mediated pyroptosis of acinar cells.