1.Effects of Substrate Stiffness on Epithelial-Mesenchymal Transition of Colon Cancer Cells under Simulated Hypoxia Environment
Jing ZHANG ; Jiajian ZHOU ; Qingya DANG ; Xinxin XU ; Yinghao LIN ; Xunxiao LI ; Haibin LI
Journal of Medical Biomechanics 2023;38(2):E261-E267
		                        		
		                        			
		                        			 Objective To explore the effects from the synergy of substrate stiffness and hypoxia on epithelial mesenchymal transition (EMT) of colon cancer cells SW480 by simulating the microenvironment of human colon cancer tissues. Methods Polyvinyl alcohol gels with different stiffness ( 4. 5, 20, 40 kPa) were prepared to simulate the stiffness of each part of colon cancer tissues. The morphological change of cells on substrate with different stiffness was detected under simulated hypoxia ( CoCl2 ) environment. The expression of hypoxia inducible factor (HIF-1α), and EMT markers E-cadherin, Vimentin, Snail 1 were detected by Western blot. The mRNA expression of E-cadherin, Vimentin, Snail 1, matrix metalloproteinase-2 ( MMP-2), and MMP-9 was detected by quantitative real-time PCR ( qRT-PCR). Results Under simulated hypoxia environment, with the increase of substrate stiffness, the SW480 cells spreading area increased, and transformed from round shape into irregular polygon. The EMT of SW480 could be enhanced through up-regulating expression of Vimentin, Snail 1, MMP-2, MMP-9, and down-regulating expression of E-cadherin. Conclusions This study is important for exploring the synergistic effect of substrate stiffness and hypoxia on the EMT of colon cancer cells as well as the molecular mechanism. 
		                        		
		                        		
		                        		
		                        	
2.A predictive model based on CT characteristics for predicting infected walled-off necrosis in acute pancreatitis
Tiegong WANG ; Jing LI ; Kai CAO ; Xu FANG ; Fang LIU ; Na LI ; Yinghao MENG ; Xiaochen FENG ; Chengwei SHAO ; Yun BIAN
Chinese Journal of Pancreatology 2022;22(1):39-47
		                        		
		                        			
		                        			Objective:To develop and verify a predictive model based on CT characteristics for predicting infected walled-off necrosis (IWON) in MSAP and SAP patients.Methods:The clinical and CT data of 1 322 patients diagnosed as MSAP and SAP according to the 2012 Atlanta revised diagnostic criteria in the First Affiliated Hospital of Naval Medical University from January 2015 to December 2020 were continuously collected. Finally, 126 patients who underwent enhanced CT scans within 3 days after admission and percutaneous catheter drainage of WON during hospitalization were enrolled. Among them, there were 63 MSAP and 63 SAP patients. According to the results of the culture from drainage fluid, the patients were divided into sterile walled-off necrosis group (SWON group, n=31) and infected walled-off necrosis group (IWON group, n=95). Patients were divided into training set (18 patients with SWON and 74 patients with IWON from January 2015 to December 2018) and validation set (13 patients with SWON and 21 patients with IWON from January 2019 to December 2020). Univariate and multivariate logistic regression analysis were performed to establish a model for predicting IWON. The model was visualized as a nomogram. The receiver operating characteristic curve (ROC) was drawn. The predictive efficacy of the model was evaluated by the area under the curve (AUC), sensitivity, specificity and accuracy, and the clinical application value was judged by decision curve analysis (DCA). Results:Univariate regression analysis showed that age, etiology, WON with bubble sign and the lowest CT value of WON were significantly associated with IWON. Multivariate logistic regression analysis showed that older age, biliary acute pancreatitis, WON with bubble sign, and the greater minimum CT value of WON were independent predictors for IWON. The formula for the prediction model was 0.12+ 0.01 age-0.75 hyperlipidemia-1.62 alcoholic-2.62 other causes+ 19.18 WON bubble sign+ 0.10 minimum CT value of WON. The AUC, sensitivity, specificity, and accuracy of the model were 0.85 (95% CI 0.76-0.94), 67.57%, 88.89%, and 71.74% in the training set and 0.78(95% CI0.62-0.94), 66.67%, 84.62%, and 73.53% in the validation set, respectively. The decision analysis curve showed that when the nomogram differentiated IWON from SWON at a rate greater than 0.38, using the nomogram could benefit the patients. Conclusions:The prediction model established based on CT characteristics might non-invasively and accurately predict the presence or absence of IWON in MSAP and SAP patients, and provide a basis for guiding treatment and evaluating prognosis.
		                        		
		                        		
		                        		
		                        	
3.Role of HCO3- umbrella in the pathogenesis of primary biliary cholangitis
Yinghao CHANG ; Dan JING ; Wenjiao XU ; Xiaolei ZHOU ; Xiaoping WANG ; Shanhong TANG
Journal of Clinical Hepatology 2021;37(3):714-717
		                        		
		                        			
		                        			 Primary biliary cholangitis (PBC) is an autoimmune disease. Although PBC has the features of autoimmune disease, it has poor response to immunosuppressants and good response to the drugs participating in bile acid metabolism, such as ursodeoxycholic acid. Studies have shown that the bicarbonate secretion of biliary epithelial cells is impaired in PBC patients, and bile acid not blocked by HCO3- umbrella enters biliary epithelial cells and mediates their damage and apoptosis, leading to the expression of autoantibodies in apoptotic cells and immunologic injury. In order to explore the role of HCO3- umbrella secreted by biliary epithelial cells in the pathogenesis of PBC, this article briefly introduces the physiological function and production mechanism of HCO3- umbrella and the influencing factors for HCO3- secretion, and it is pointed out that reduced HCO3- secretion may be a key link in the pathogenesis of PBC and a potential therapeutic target. 
		                        		
		                        		
		                        		
		                        	
4.MRI characteristics and malignancy risk prediction model for intraductal papillary mucinous neoplasm of the pancreas
Xu FANG ; Jing LI ; Tiegong WANG ; Na LI ; Yinghao MENG ; Xiaochen FENG ; Yun BIAN ; Chengwei SHAO ; Jianping LU ; Li WANG
Chinese Journal of Pancreatology 2021;21(6):426-432
		                        		
		                        			
		                        			Objective:To investigate the MRI features of intraductal papillary mucinous tumor (IPMN) of the pancreas and establish a prediction model for predicting the malignancy risk.Methods:The clinical data of 260 IPMN patients who underwent MRI and pathological confirmed in the First Affiliated Hospital of Naval Medical University from October 2012 to April 2020 were retrospectively analyzed. According to the pathological results, all patients were divided into benign group (including IPMN with low-grade dysplasia) and malignant group (including IPMN with high grade dysplasia and invasive carcinoma). According to international consensus of prediction model modeling, patients were divided into training set and validation set in chronological order. A prediction model was developed based on a training set consisting of 193 patients (including 117 patients with benign IPMN and 76 patients with malignant IPMN) between October 2012 and April 2019, and the model was validated in 67 patients (including 40 patients with benign IPMN and 27 patients with malignant IPMN) between May 2019 and April 2020. The multivariable logistic regression model was adopted to identify the independent predictive factors for IPMN malignancy and establish and visualized a nomogram. The ROC was drawn and AUC was calculated. The decision curve analysis was used to evaluate its clinical usefulness.Results:The IPMN type, cyst size, thickened cyst wall, mural nodule size, diameter of main pancreatic duct (MPD) and the abrupt change in the caliber of the MPD with distal pancreatic atrophy in the training set and validation set, and jaundice and lymphadenopathy in the training set were significantly different between benign group and malignant group ( P<0.05). The multivariable logistic regression model of characteristics included the jaundice, cyst size, mural nodule size ≥5 mm, the abrupt change in caliber of the MPD with distal pancreatic atrophy were independent risk factors for IPMN maligancy. The model for predicting IPMN malignancy was -0.35+ 2.28×(jaundice)+ 1.57×(mural nodule size ≥5 mm)+ 2.92×(the abrupt change in caliber of the MPD with distal pancreatic atrophy)-1.95×(cyst <3 cm)-1.05×(cyst≥3 cm). The individualized prediction nomogram using these predictors of the malignant IPMN achieved an AUC of 0.85 (95% CI 0.79-0.91) in the training set and 0.84 (95% CI 0.74-0.94) in the validation set. The sensitivity, specificity and accuracy of the training set were 72.37%, 85.47% and 80.31%, respectively. The sensitivity, specificity and accuracy of the validation set were 81.48%, 75.00% and 77.61%, respectively. The decision curve analysis demonstrated that when the IPMN malignancy rate was >0.16, the nomogram diagnosing IPMN could benefit patients more than the strategy of considering all the patients as malignancy or non-malignancy. Conclusions:The nomogram based on MRI features can accurately predict the risk of malignant IPMN, and can be used as an effective predictive tool to provide more accurate information for personalized diagnosis and treatment of patients.
		                        		
		                        		
		                        		
		                        	
5.Development of a computed tomography nomogram for differentiating focal-type autoimmune pancreatitis from pancreatic ductal adenocarcinoma
Jing LI ; Mengmeng ZHU ; Jian ZHOU ; Yinghao MENG ; Xiaochen FENG ; Li WANG ; Chengwei SHAO ; Jianping LU ; Yun BIAN ; Jing SHENG
Chinese Journal of Pancreatology 2021;21(6):448-454
		                        		
		                        			
		                        			Objective:To develop and validate a visualized computed tomography nomogram for differentiating focal-type autoimmune pancreatitis (fAIP) from pancreatic ductal adenocarcinoma (PDAC).Methods:This retrospective review included 42 consecutive patients with fAIP diagnosed according to the International Consensus Diagnostic Criteria and 242 consecutive patients with PDAC confirmed by pathology between January 2011 and December 2018 in the First Affiliated Hospital of Naval Medical University. Among them, 209 consecutive patients (25 fAIP and 184 PDAC) were enrolled in the development cohort; Seventy-five consecutive patients (17 fAIP and 58 PDAC) were enrolled in the validation cohort. CT image characteristics, including lesion location, size, enhancement mode and degree of mass enhancement in portal vein phase, pancreatic parenchymal atrophy, main pancreatic duct dilation, common bile duct dilation, cyst, acute obstructive pancreatitis, and vascular invasion were compared. Univariate and multivariate analysis were used to screen the independent predictive factors for fAIP and PDAC, based on which the nomogram was constructed and visualized. The receiver operating characteristic curve (ROC) was drawn and area under the curve (AUC) was calculated to evaluate the differential efficacy of the nomogram. The clinical usefulness of the nomogram was evaluated by decision curve analysis.Results:There were statistically significant differences on common bile duct dilation and the mode and degree of enhancement in portal phase between fAIP group and PDAC group in training set and validation set ( P<0.05). Univariate regression analysis showed that common bile duct dilation and degree of mass enhancement in portal vein were closely correlated with fAIP and PDAC phase between the two groups in training set and validation set; mass enhancement mode in portal vein phase and main pancreatic duct dilation were closely correlated with fAIP and PDAC in training set. Multivariate logistic regression analysis showed that common biliary duct dilatation ( OR=0.26, 95% CI 0.06-1.10, P=0.07), main pancreatic duct dilation ( OR=9.46, 95% CI 1.60-56.04, P<0.01) and mass mild hyper-enhancing in portal vein phase ( OR=0.003, 95% CI 0.0003-0.0278, P<0.0001) were the three independent predictors for fAIP and PDAC. Thus, the equation for predicting the probability of PDAC was 4.51-1.33× no dilatation of the common bile duct+ 2.25× the main pancreatic duct dilated-5.84× mass mild hyper-enhancing during the portal phase. The individualized prediction nomogram using these predictors of the fAIP achieved an AUC of 0.97 (95% CI 0.95-0.99) in the development set and 0.97(95% CI0.94-1.00) in the validation set. The sensitivity, specificity and accuracy of the model were 87.5%, 100% and 89% in the training set; and 94.83%, 94.12% and 94.67% in the validation set, respectively. The decision curve analysis demonstrated that the nomogram was clinically useful when the nomogram differentiated fAIP and PDAC at a rate of >0.2. Conclusions:The nomogram based on common bile duct dilation, main pancreatic duct dilation and mass enhancement in portal vein phase can be used as a useful tool for predicting fAIP and PDAC and provide valuable evidence for clinical decision.
		                        		
		                        		
		                        		
		                        	
6.Correlation between HLA-DQB1 and HLA-DRB1 gene polymorphisms and caries: a systematic review and Meta-analysis
CHEN Yue ; WU Zeyu ; MO Yanli ; JING Yinghao ; LIU Yishan
Journal of Prevention and Treatment for Stomatological Diseases 2021;29(12):820-827
		                        		
		                        			Objective:
		                        			Systematic evaluation of the correlation of HLA-DQB1 and HLA-DRB1 allele polymorphisms with caries, to provide reference for caries prevention and treatment. 
		                        		
		                        			Methods:
		                        			 Relevant literature published before December 2020 was searched in the Cochrane Library, PubMed, Embase, Web of Science, Scopus, CNKI, Wanfang, VIP, and CBM databases. Meta-analysis was performed using the R4.0.2 software to test for heterogeneity and evaluate the publication bias.
		                        		
		                        			Results :
		                        			 In total,10 case-control studies were included with 564 people in the case group and 676 people in the control group. The results of the Meta-analysis show that: ① HLA-DQB1*02 (OR=0.52, 95%CI=0.29-0.93, P < 0.05) and HLA-DRB1*09 (OR=0.34, 95%CI=0.21-0.58, P < 0.05) are protective factors of dental caries; ② HLA-DRB1*13 (OR=2.96, 95%CI=2.03-4.33, P < 0.05) and HLA-DRB1*14 (OR=1.95, 95%CI=1.26-3.02, P < 0.05) alleles are risk factors for the development of dental caries. The results of the subgroup analysis are: HLA-DRB1*07 is a caries susceptibility factor in the Chinese population (OR=0.48, 95% CI=0.24-0.97, P < 0.05), while it is not statistically significant in the Brazilian and Turkish populations; HLA-DRB1*11 is a caries protective factor in the saliva group (OR=2.26, 95% CI=1.46-3.52, P < 0.05). 3.52, P < 0.001), while it is a caries susceptibility factor in the blood group (OR=0.09, 95% CI=0.12-0.34, P < 0.001). 
		                        		
		                        			Conclusion 
		                        			HLA-DRB1*13 and HLA-DRB1*14 alleles are caries susceptibility genes, and HLA-DQB1*02 and HLA-DRB1*09 have protective effects on the caries development. HLA-DRB1*07 is a caries susceptibility gene in the Chinese population; HLA-DRB1*11 is a caries protective gene in the saliva group. Due to the limited sample size and quality of the included studies, more high-quality studies will be included later for verification.
		                        		
		                        		
		                        		
		                        	
7.Influences of gender, age, and body mass index on the arterial stiffness in hypertensive patients
Yinghao SHEN ; Junfeng ZHANG ; Jing ZHOU ; Xin RONG ; Hua GUO ; Qing GU ; Cailan ZHANG
Journal of Chinese Physician 2013;(4):465-468
		                        		
		                        			
		                        			Objective To investigate the influences of gender,age,and body mass index (BMI)on the arterial stiffness in hypertensive patients.Methods A total of 1026 hypertensive patients were enrolled in this study from 6 community health centers in Baoshan District and Shanghai Third People's Hospital.The Related medical histories and carotid-femoral(C-F) pulse wave velocity (PWV) were recorded and PWV were re-tested in 672 patients after 1 year's follow-up.The C-F PWV was analyzed from different group of Gender,age and BMI at baseline and after follow up.Results (1)C-F PWV of the male hypertensive patients were higher than that of female's and the corresponding figures were (13.63 ±3.07)m/s and (12.59±2.85)m/s(P <0.01).After one year's follow up,C-F PWV was increased in both male and female with corresponding figures of (14.11 ± 3.58) m/s and (13.51 ± 3.56) m/s (P < 0.05).(2) The C-F PWV was increased with age.The corresponding figures were [(11.11 ± 2.00) m/s for age group 30 ~ 50 years old,(12.73 ± 2.77) m/s for age group > 50 ~ 70 years old,and (14.74 ± 3.29) m/s for age group > 70 years old,all P <0.01].After one year's follow-up,C-F PWV of three age groups was increased and the corresponding figures were [(11.36±1.78)m/s(P >0.05),(13.39±3.33)m/s(P <0.01),and (15.68 ±3.94)m/s(P <0.05)].The increased range of C-F PWV (from high to low) was age group > 70,age group > 50 ~70 and age group 30 ~50.(3) C-F PWV of patients with BMI ≥ 24 kg/m2 was significantly lower than that of patients with BMI <24 kg/m2 and the corresponding figures were [(12.93 ±2.89)m/s and (13.39 ±3.18)m/s,P <0.05].After one year's follow up,C-F PWV was increased and the figures were [(13.54 ± 3.54) rn/s and (14.27±3.61) m/s,respectively(P <0.01)].Conclusions Except BMI,gender and age were the important influence factors on arterial stiffness.
		                        		
		                        		
		                        		
		                        	
8.Anti-allergic effects of xuebijing and potential role of heme oxygenase-1 against ovalbumin-induced murine allergic rhinitis model.
Dongmei SONG ; Yinghao NIU ; Jiantao WANG ; Jing XUE ; Xin LV ; Jianwang YANG ; Baoshan WANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2013;27(16):899-904
		                        		
		                        			OBJECTIVE:
		                        			In this study, we investigated the anti-inflammation effects of Xuebijing in OVA-induced murine allergic rhinitis model. Furthermore, we determined whether heme oxygenase (HO)-1 is required for the protective activity of Xuebijing.
		                        		
		                        			METHOD:
		                        			Airways of OVA-sensitized mice exposed to OVA challenge developed eosinophilia, mucus hypersecretion and increased cytokine levels. Levels of interleukin IL-4, IL-5, IL-13, and tumor necrosis factor (TNF)-alpha in nasal lavage fluid were measured using enzyme-linked immunosorbent assays (ELISAs). Lung tissue and nasal mucosa sections were stained with Mayer's hematoxylin and eosin for assessment of cell infiltration and mucus production, Immunohistochemistry, Real-time PCR and Western Blot analyses for HO-1 protein expression.
		                        		
		                        			RESULT:
		                        			Orally administered Xuebijing significantly inhibited the number of OVA-induced inflammatory cells and IgE production, along with reduced T-helper (Th) 2 cytokine levels, such as IL-4, IL-5 and IL-13, improved the level of IFN-gamma, in nasal lavage fluid. In addition, Xuebijing induced a marked decrease in OVA-induced inflammatory cell infiltration and mucus production in nasal and lung tissues. These effects were correlated with HO-1 mRNA and protein induction.
		                        		
		                        			CONCLUSION
		                        			Our results indicate that Xuebijing protects against OVA-induced airway inflammation, at least in part, via HO-1 upregulation.
		                        		
		                        		
		                        		
		                        			Animals
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		                        			Drugs, Chinese Herbal
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		                        			pharmacology
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		                        			therapeutic use
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		                        			Eosinophilia
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		                        			metabolism
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		                        			Heme Oxygenase-1
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		                        			metabolism
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		                        			Immunoglobulin E
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		                        			immunology
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		                        			Inflammation
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		                        			drug therapy
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		                        			metabolism
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		                        			Interleukin-13
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		                        			metabolism
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		                        			Interleukin-4
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		                        			metabolism
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		                        			Interleukin-5
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		                        			metabolism
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		                        			Membrane Proteins
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		                        			metabolism
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		                        			Mice
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		                        			Nasal Mucosa
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		                        			metabolism
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		                        			Rhinitis, Allergic
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		                        			Rhinitis, Allergic, Perennial
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		                        			chemically induced
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		                        			drug therapy
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		                        			metabolism
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		                        			Tumor Necrosis Factor-alpha
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		                        			metabolism
		                        			
		                        		
		                        	
9.Hypertension intervention program organized by tertiary hospitals with community health centers
Jing ZHOU ; Junfeng ZHANG ; Yinghao SHEN ; Jincheng HUANG ; Haihong TANG ; Meijuan YUAN ; Ping WANG ; Jiewen XIAO ; Deying ZHANG
Chinese Journal of General Practitioners 2012;11(9):689-691
		                        		
		                        			
		                        			Five hundred and nineteen patients with essential hypertension from 6 community health centers in Baoshan Distract of Shanghai were enrolled in the program,all patients received direct or indirect comprehensive interventions.These interventions were conducted by doctors from tertiary hospitals and community health serwice centers.Among these hyperpietic,462 patients were followed-up for 1 year.After interventions,the awareness rate of hypertension was significantly increased,unhealthy life styles were changed; blood pressure control rate and risk factors control rate were also increased; carotid-femoral artery pulse wave velocity and carotid-radial artery pulse wave velocity were decreased (P < 0.01 or P < 0.05).The results indicate that comprehensive interventions organized by tertiary hospitals with community health centers are effectivc in managcmcnt of hypcrtension.
		                        		
		                        		
		                        		
		                        	
            

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