Maternal Separation Induced Visceral Hypersensitivity from Childhood to Adulthood

( Lisha Yi ),( Haiqin Zhang ),( Huihui Sun ),( Lu Zhou ),( Ying Chen ),( Liqian Xuan ),( Yuanxi Jiang ),( Shuchang Xu ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2017 Journal of Neurogastroenterology and Motility (JNM Vol.23 No.2

Background/Aims Early adverse life events (EALs) are relevant to irritable bowel syndrome in adulthood. Maternal separation (MS), as one of the EALs, has proved to induce visceral hypersensitivity in adult rats. However, the effect of MS on visceral hypersensitvity from the post-weaning period to adulthood remains unknown. Methods One hundred and ten neonatal Sprague-Dawley rats were randomly divided into 2 groups: rats in the MS group were exposed to 3 hours daily MS on postnatal day (PND) 2-14; the normal control (NC) group remained undisturbed. Visceral sensitivity was determined by measuring the visceromotor response to colorectal distention on PND21, 35, and 56. Anxiety-like behaviors were measured by the open field test. Results Compared with NC rats, MS rats showed significant visceral hypersensitivity from the post-weaning period to adult. The proportion of visceral hypersensitive rats decreased with age from 87.5% to 70.0% in the female MS group and from 90.0% to 66.7% in the male MS group. The relative VMR ratio of MS and NC on PND21 was higher than PND35 and PND56. MS rats showed decreased ability of movement and exploration to the novel environment in the post-weaning period, obesity in the prepubertal period, and more anxietylike behaviors in adulthood. Conclusions MS can significantly affect visceral sensitivity and behaviors of rats in different age stages, especially in the post-weaning period. Visceral hypersensitivity of MS rats is more pronounced in the post-weaning period and slightly restored in adults. Thus, visceral hypersensitivity in the post-weaning period might play a more meaningful pathophysiologic role in the formation of adult irritable bowel syndrome. (J Neurogastroenterol Motil 2017;23:306-315)

Establishment of a novel myocarditis mouse model based on cyclosporine A

Zhao Tian Hao,Jiang Yi Xuan,Chen Kai Qin,Qiu Dan,Xu Yan Zhe,Ye Chun,Ren Ting,Zhang Bo,Dai Bin,Hu Jue,Lu Jun,Zhou Fang Liang,Xiao Rong,Lu Fang Guo,Wei Ke 한국유전학회 2022 Genes & Genomics Vol.44 No.12

Background: Myocarditis is a myocardial injury that can easily cause adolescent death. Traditional research models of animal invasion with viral components, lipopolysaccharide (LPS) or porcine myocardial myosin, among others, have the shortcomings of potential biological safety hazards and high animal mortality. Objective: To explore the construction of a novel myocarditis model with cyclosporine A and the potential genes and pathways associated with it. Methods: BALB/c mice were used in this study, and cyclosporin A and LPS were injected into the peritoneal cavity of mice. The successful establishment of the model was assessed by detecting serum myocardial injury markers and inflammatory factors levels, HE, IHC staining, and RT-qPCR methods. Key genes were obtained using the GSE35182 dataset from the GEO database and validated with the RT-qPCR method. Results: We found that a large number of inflammatory cells infiltrated the myocardium of mice in each group of Cyclosporin A constructed model, while the expression of inflammatory factor indicators was increased, and this model has the characteristics of high degree of local inflammation in myocardial tissue, low mortality, and safe and non-toxic treatment. Using GSE35182 data, we selected 18 Hub genes and validated Hub genes in myocardial tissue with RT-qPCR and found that multiple signaling pathways such as Toll-likereceptor signaling pathway(TLRs), Rap1 signal pathway(Rap1), and Chemokine signaling pathway may be involved in the development of myocarditis. Conclusion: Cyclosporin A can construct a new myocarditis model, and TLRs, Chemokines and Rap1 signaling pathways may be the core pathways of myocarditis.

Tumor Location Causes Different Recurrence Patterns in Remnant Gastric Cancer

Sun Bo,Zhang Haixian,Wang Jiangli,Cai Hong,Xuan Yi,Xu Dazhi 대한위암학회 2022 Journal of gastric cancer Vol.22 No.4

Purpose Tumor recurrence is the principal cause of poor outcomes in remnant gastric cancer (RGC) after resection. We sought to elucidate the recurrent patterns according to tumor locations in RGC. Materials and Methods Data were collected from the Shanghai Cancer Center between January 2006 and December 2020. A total of 129 patients with RGC were included in this study, of whom 62 had carcinomas at the anastomotic site (group A) and 67 at the non-anastomotic site (group N). The clinicopathological characteristics, surgical results, recurrent diseases, and survival were investigated according to tumor location. Results The time interval from the previous gastrectomy to the current diagnosis was 32.0±13.0 and 21.0±13.4 years in groups A and N, respectively. The previous disease was benign in 51/62 cases (82.3%) in group A and 37/67 cases (55.2%) in group N (P=0.002). Thirty-three patients had documented sites of tumor recurrence through imaging or pathological examinations. The median time to recurrence was 11.0 months (range, 1.0–35.1 months). Peritoneal recurrence occurred in 11.3% (7/62) of the patients in group A versus 1.5% (1/67) of the patients in group N (P=0.006). Hepatic recurrence occurred in 3.2% (2/62) of the patients in group A versus 13.4% (9/67) of the patients in group N (P=0.038). Patients in group A had significantly better overall survival than those in group N (P=0.046). Conclusions The tumor location of RGC is an essential factor for predicting recurrence patterns and overall survival. When selecting an optimal postoperative follow-up program for RGC, physicians should consider recurrent features according to the tumor location. Purpose Tumor recurrence is the principal cause of poor outcomes in remnant gastric cancer (RGC) after resection. We sought to elucidate the recurrent patterns according to tumor locations in RGC. Materials and Methods Data were collected from the Shanghai Cancer Center between January 2006 and December 2020. A total of 129 patients with RGC were included in this study, of whom 62 had carcinomas at the anastomotic site (group A) and 67 at the non-anastomotic site (group N). The clinicopathological characteristics, surgical results, recurrent diseases, and survival were investigated according to tumor location. Results The time interval from the previous gastrectomy to the current diagnosis was 32.0±13.0 and 21.0±13.4 years in groups A and N, respectively. The previous disease was benign in 51/62 cases (82.3%) in group A and 37/67 cases (55.2%) in group N (P=0.002). Thirty-three patients had documented sites of tumor recurrence through imaging or pathological examinations. The median time to recurrence was 11.0 months (range, 1.0–35.1 months). Peritoneal recurrence occurred in 11.3% (7/62) of the patients in group A versus 1.5% (1/67) of the patients in group N (P=0.006). Hepatic recurrence occurred in 3.2% (2/62) of the patients in group A versus 13.4% (9/67) of the patients in group N (P=0.038). Patients in group A had significantly better overall survival than those in group N (P=0.046). Conclusions The tumor location of RGC is an essential factor for predicting recurrence patterns and overall survival. When selecting an optimal postoperative follow-up program for RGC, physicians should consider recurrent features according to the tumor location.

Apatinib Combined with Local Irradiation Leads to Systemic Tumor Control via Reversal of Immunosuppressive Tumor Microenvironment in Lung Cancer

Li-jun Liang,Chen-xi Hu,Yi-xuan Wen,Xiao-wei Geng,Ting Chen,Guo-qing Gu,Lei Wang,You-you Xia,Yong Liu,Jia-yan Fei,Jie Dong,Feng-hua Zhao,Yiliyar Ahongjiang,Kai-yuan Hui,Xiao-dong Jiang 대한암학회 2020 Cancer Research and Treatment Vol.52 No.2

Purpose This study aimed to investigate the potential systemic antitumor effects of stereotactic ablative radiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor 2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma. Materials and Methods Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor; irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grew to the touchable size, mice were randomly divided into eight treatment groups. These groups received normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200 mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not to the primary tumor. The further tumor growth/regression of mice were followed and observed. Results For the single 15 Gy modality, tumor growth delay could only be observed at the primary tumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primary and secondary tumor growth could be observed, indicated an abscopal effect was induced. Mechanism analysis suggested that programmed death-ligand 1 expression increased with SABR was counteract by additional apatinib therapy. Furthermore, when apatinib was combined with SABR, the composition of immune cells could be changed. More importantly, this two-pronged approach evoked tumor antigen–specific immune responses and the mice were resistant to another tumor rechallenge, finally, long-term survival was improved. Conclusion Our results suggested that the tumor microenvironment could be managed with apatinib, which was effective in eliciting an abscopal effect induced by SABR.

Tumor Location Causes Different Recurrence Patterns in Remnant Gastric Cancer

Sun, Bo,Zhang, Haixian,Wang, Jiangli,Cai, Hong,Xuan, Yi,Xu, Dazhi The Korean Gastric Cancer Association 2022 Journal of gastric cancer Vol.22 No.-

Purpose: Tumor recurrence is the principal cause of poor outcomes in remnant gastric cancer (RGC) after resection. We sought to elucidate the recurrent patterns according to tumor locations in RGC. Materials and Methods: Data were collected from the Shanghai Cancer Center between January 2006 and December 2020. A total of 129 patients with RGC were included in this study, of whom 62 had carcinomas at the anastomotic site (group A) and 67 at the non-anastomotic site (group N). The clinicopathological characteristics, surgical results, recurrent diseases, and survival were investigated according to tumor location. Results: The time interval from the previous gastrectomy to the current diagnosis was 32.0±13.0 and 21.0±13.4 years in groups A and N, respectively. The previous disease was benign in 51/62 cases (82.3%) in group A and 37/67 cases (55.2%) in group N (P=0.002). Thirty-three patients had documented sites of tumor recurrence through imaging or pathological examinations. The median time to recurrence was 11.0 months (range, 1.0-35.1 months). Peritoneal recurrence occurred in 11.3% (7/62) of the patients in group A versus 1.5% (1/67) of the patients in group N (P=0.006). Hepatic recurrence occurred in 3.2% (2/62) of the patients in group A versus 13.4% (9/67) of the patients in group N (P=0.038). Patients in group A had significantly better overall survival than those in group N (P=0.046). Conclusions: The tumor location of RGC is an essential factor for predicting recurrence patterns and overall survival. When selecting an optimal postoperative follow-up program for RGC, physicians should consider recurrent features according to the tumor location.

Wnt/β-Catenin Promotes the Osteoblastic Potential of BMP9 Through Down-Regulating Cyp26b1 in Mesenchymal Stem Cells

Yao Xin-Tong,Li Pei-pei,Liu Jiang,Yang Yuan-Yuan,Luo Zhen-Ling,Jiang Hai-Tao,He Wen-Ge,Luo Hong-Hong,Deng Yi-Xuan,He Bai-Cheng 한국조직공학과 재생의학회 2023 조직공학과 재생의학 Vol.20 No.5

BACKGROUND: All-trans retinoic acid (ATRA) promotes the osteogenic differentiation induced by bone morphogenetic protein 9 (BMP9), but the intrinsic relationship between BMP9 and ATRA keeps unknown. Herein, we investigated the effect of Cyp26b1, a critical enzyme of ATRA degradation, on the BMP9-induced osteogenic differentiation in mesenchymal stem cells (MSCs), and unveiled possible mechanism through which BMP9 regulates the expression of Cyp26b1. METHODS: ATRA content was detected with ELISA and HPLC–MS/MS. PCR, Western blot, and histochemical staining were used to assay the osteogenic markers. Fetal limbs culture, cranial defect repair model, and micro–computed tomographic were used to evaluate the quality of bone formation. IP and ChIP assay were used to explore possible mechanism. RESULTS: We found that the protein level of Cyp26b1 was increased with age, whereas the ATRA content decreased. The osteogenic markers induced by BMP9 were increased by inhibiting or silencing Cyp26b1 but reduced by exogenous Cyp26b1. The BMP9-induced bone formation was enhanced by inhibiting Cyp26b1. The cranial defect repair was promoted by BMP9, which was strengthened by silencing Cyp26b1 and reduced by exogenous Cyp26b1. Mechanically, Cyp26b1 was reduced by BMP9, which was enhanced by activating Wnt/b-catenin, and reduced by inhibiting this pathway. b-catenin interacts with Smad1/5/9, and both were recruited at the promoter of Cyp26b1. CONCLUSIONS: Our findings suggested the BMP9-induced osteoblastic differentiation was mediated by activating retinoic acid signalling, viadown-regulating Cyp26b1. Meanwhile, Cyp26b1 may be a novel potential therapeutic target for the treatment of bone-related diseases or accelerating bone-tissue engineering.

Study on the micro-scale simulation of wind field over complex terrain by RAMS/FLUENT modeling system

Li, Lei,Zhang, Li-Jie,Zhang, Ning,Hu, Fei,Jiang, Yin,Xuan, Chun-Yi,Jiang, Wei-Mei Techno-Press 2010 Wind and Structures, An International Journal (WAS Vol.13 No.6

A meteorological model, RAMS, and a commercial computational fluid dynamics (CFD) model, FLUENT are combined as a one-way off-line nested modeling system, namely, RAMS/FLUENT system. The system is experimentally applied in the wind simulation over a complex terrain, with which numerical simulations of wind field over Foyeding weather station located in the northwest mountainous area of Beijing metropolis are performed. The results show that the method of combining a meteorological model and a CFD model as a modeling system is reasonable. In RAMS/FLUENT system, more realistic boundary conditions are provided for FLUENT rather than idealized vertical wind profiles, and the finite volume method (FVM) of FLUENT ensures the capability of the modeling system on describing complex terrain in the simulation. Thus, RAMS/FLUENT can provide fine-scale realistic wind data over complex terrains.

Study on the micro-scale simulation of wind field over complex terrain by RAMS/FLUENT modeling system

Lei Li,Li-Jie Zhang,Ning Zhang,Fei Hu,Yin Jiang,Chun-Yi Xuan,Wei-Mei Jiang 한국풍공학회 2010 Wind and Structures, An International Journal (WAS Vol.13 No.6

A meteorological model, RAMS, and a commercial computational fluid dynamics (CFD) model, FLUENT are combined as a one-way off-line nested modeling system, namely, RAMS/FLUENT system. The system is experimentally applied in the wind simulation over a complex terrain, with which numerical simulations of wind field over Foyeding weather station located in the northwest mountainous area of Beijing metropolis are performed. The results show that the method of combining a meteorological model and a CFD model as a modeling system is reasonable. In RAMS/FLUENT system, more realistic boundary conditions are provided for FLUENT rather than idealized vertical wind profiles, and the finite volume method (FVM) of FLUENT ensures the capability of the modeling system on describing complex terrain in the simulation. Thus, RAMS/FLUENT can provide fine-scale realistic wind data over complex terrains.

Evaluation of Renal Pathophysiological Processes Induced by an Iodinated Contrast Agent in a Diabetic Rabbit Model Using Intravoxel Incoherent Motion and Blood Oxygenation Level-Dependent Magnetic Resonance Imaging

Yongfang Wang,Xin Zhang,Bin Wang,Yang Xie,Yi Wang,Xuan Jiang,Rongjia Wang,Ke Ren 대한영상의학회 2019 Korean Journal of Radiology Vol.20 No.5

Objective: To examine the potential of intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) magnetic resonance imaging for detecting renal changes after iodinated contrast-induced acute kidney injury (CI-AKI) development in a diabetic rabbit model. Materials and Methods: Sixty-two rabbits were randomized into 2 groups: diabetic rabbits with the contrast agent (DCA) and healthy rabbits with the contrast agent (NCA). In each group, 6 rabbits underwent IVIM and BOLD imaging at 1 hour, 1 day, 2 days, 3 days, and 4 days after an iohexol injection while 5 rabbits were selected to undergo blood and histological examinations at these specific time points. Iohexol was administrated at a dose of 2.5 g I/kg of body weight. Further, the apparent transverse relaxation rate (R2*), average pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were calculated. Results: The D and f values of the renal cortex (CO) and outer medulla (OM) were significantly decreased compared to baseline values in the 2 groups 1 day after the iohexol injection (p < 0.05). A marked reduction in the D* values for both the CO and OM was also observed after 1 hour in each group (p < 0.05). In the OM, a persistent elevation of the R2* was detected for 4 days in the DCA group (p < 0.05). Histopathological changes were prominent, and the pathological features of CI-AKI aggravated in the DCA group until day 4. The D, f, and R2* values significantly correlated with the histological damage scores, hypoxiainducible transcription factor-1α expression scores, and serum creatinine levels. Conclusion: A combination of IVIM and BOLD imaging may serve as a noninvasive method for detecting and monitoring CIAKI in the early stages in the diabetic kidney.

Relationships of Low Serum Levels of Interleukin-10 With Poststroke Anxiety and Cognitive Impairment in Patients With Clinical Acute Stroke

Zhao-jian Ying,Yuan-Yuan Huang,Meng-Meng Shao,Chu-Huai Chi,Ming-Xia Jiang,Yi-Hui Chen,Yu-Chen,Miao-Xuan Sun,Yan-Yan Zhu,Xianmei Li 대한신경과학회 2023 Journal of Clinical Neurology Vol.19 No.3

Background and Purpose The relationships among interleukin (IL)-10 levels, anxiety, and cognitive status after stroke remain controversial. We aimed to determine the associations of serum IL-10 levels with poststroke anxiety (PSA) and poststroke cognitive impairment (PSCI). Methods We recruited 350 patients with stroke, of whom only 151 completed a 1-month follow- up assessment. The Mini Mental State Examination (MMSE) and Hamilton Anxiety Scale (HAMA) were used to assess the cognitive status and anxiety, respectively. Serum IL-10 levels were measured within 24 hours of admission. Results IL-10 levels were significantly lower in the PSA group than in the non-PSA group, and they were negatively associated with HAMA scores (r=-0.371, p<0.001). After adjusting for all potential confounders, IL-10 levels remained an independent predictor of PSA (odds ratio=0.471, 95% confidence interval=0.237–0.936, p=0.032). IL-10 levels were strongly correlated with behavior during interviews, psychic anxiety, and somatic anxiety. Patients without PSCI had higher IL-10 levels were higher in non-PSCI patients than in PSCI patients, and they were positively associated with MMSE scores in the bivariate correlation analysis (r=0.169, p=0.038), and also with memory capacity, naming ability, and copying capacity. However, IL-10 did not predict PSCI in the univariable or multivariable logistic regression. Conclusions Low IL-10 levels were associated with increased risks of PSA and PSCI at a 1-month follow-up after stroke. Serum IL-10 levels may therefore be helpful in predicting PSA.