1.Effects of phthalates on expressions of heme oxygenase-1(HO-1)in HepG2 cells and construction of a HO-1-based 3D-QSAR model
Huan LIU ; Kangxing LI ; Wenjie WENG ; Yujun SHI ; Chunhong LIU ; Zhenyi NONG
Chinese Journal of Pharmacology and Toxicology 2025;39(9):681-688
OBJECTIVE To evaluate the effects of phthalic acid esters(PAEs)on the expression of heme oxygenase-1(HO-1)in HepG2 cells,and to construct an HO-1-based three-dimensional quantita-tive structure-activity relationship(3D-QSAR)model.METHODS ① HepG2 cells were treated with seven types of PAEs:di-(2-ethylhexyl)phthalate(DEHP),di-n-octyl phthalate(DnOP),dimethyl phthalate(DMP),diethyl phthalate(DEP),dihexyl phthalate(DHXP),dimethylglycol phthalate(DMEP),and dibutyl phthalate(DBP),at final concentrations of 0(DMSO,solvent control),0.062 5,0.125,0.25,0.5 and 1 mmol·L-1(n=6)for 48 h at 37℃.The expression level of HO-1 was measured by Western blotting.② A 3D-QSAR model was constructed using comparative molecular similarity indices analysis(CoMSIA)based on the measured HO-1 levels.The applicability domain(AD)of the model was evaluated using the leverage method.Model fitting quality and predictive ability were evaluated via the KNIME Enalos+node to verify model stability.Additionally,molecular docking was performed to validate the binding interactions between PAEs and HO-1.RESULTS ① Compared with the solvent control group,48 h of exposure to 0.062 5 mmol·L-1 PAEs(DMP,DMEP,DEHP,DnOP and DEP)significantly increased HO-1 protein expressions,while 1 mmol·L-1 PAEs(DMP,DBP,DnOP,DEP and DHXP)significantly suppressed HO-1 expressions.② The 3D-QSAR model showed a non-cross-validated coefficient(R2)of 0.996 and a cross-validated coefficient(Q2)of 0.548.All the seven PAEs in the 3D-QSAR model were within the applicability domain(AD)and passed external validation.Molecular docking results indi-cated that DBP,DnOP,DEHP and DHXP exhibited stronger binding affinities to HO-1.CONCLUSION Forty-eight hours of exposure of HepG2 cells to 1 mmol·L-1 PAEs can significantly suppress HO-1 expres-sions.The 3D-QSAR model established in this study provides a potential tool for predicting the HO-1-related toxic effects of novel PAEs.
2.Application value of needle-knife accurate fistulotomy for difficult biliary cannulation during endoscopic retrograde cholangiopancreatography
Yijun SHU ; Hao WENG ; Mingzhe WENG ; Wenjie ZHANG ; Mingning ZHAO ; Jun GU ; Xuefeng WANG
Chinese Journal of Digestive Surgery 2025;24(7):905-911
Objective:To investigate the application value of needle-knife accurate fistulo-tomy (NKAF) for difficult biliary cannulation during endoscopic retrograde cholangiopancreato-graphy (ERCP).Methods:The retrospective and descriptive study was conducted. The clinicopatho-logical data of 137 patients with difficult biliary cannulation during ERCP at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between January 2021 and December 2022 were collected. There were 51 males and 86 females, aged (69±13)years. All 137 patients received NKAF for cannulation during ERCP. Observation indicators: (1) surgical situations; (2) complications. Measurement data with normal distribution were represented as Mean± SD. Count data were repre-sented as absolute numbers. Results:(1) Surgical situations. Of 137 patients, 136 cases had succe-ssful cannulation, 1 case had failed cannulation with NKAF following unsuccessful double-guidewire technique. In the 136 successful cases, the endoscope was straightened in 42 cases, left in a long position in 37 cases, and maintained in the standard position in 57 cases. The cannulation time was (90±8)s. (2) Complications. The serum amylase at postoperative 6 hours in the 136 successful cases was (163±23)U/L. No patient developed post-ERCP pancreatitis. Of the 136 patients with successful cannulation, one case experienced post-sphincterotomy bleeding, which was observed oozing from the papillary orifice on emergency gastroscopy. The patient was successfully controlled with endoscopic clips.Conclusion:NKAF is safe and effective for difficult biliary cannulation during ERCP.
3.Effects of phthalates on expressions of heme oxygenase-1(HO-1)in HepG2 cells and construction of a HO-1-based 3D-QSAR model
Huan LIU ; Kangxing LI ; Wenjie WENG ; Yujun SHI ; Chunhong LIU ; Zhenyi NONG
Chinese Journal of Pharmacology and Toxicology 2025;39(9):681-688
OBJECTIVE To evaluate the effects of phthalic acid esters(PAEs)on the expression of heme oxygenase-1(HO-1)in HepG2 cells,and to construct an HO-1-based three-dimensional quantita-tive structure-activity relationship(3D-QSAR)model.METHODS ① HepG2 cells were treated with seven types of PAEs:di-(2-ethylhexyl)phthalate(DEHP),di-n-octyl phthalate(DnOP),dimethyl phthalate(DMP),diethyl phthalate(DEP),dihexyl phthalate(DHXP),dimethylglycol phthalate(DMEP),and dibutyl phthalate(DBP),at final concentrations of 0(DMSO,solvent control),0.062 5,0.125,0.25,0.5 and 1 mmol·L-1(n=6)for 48 h at 37℃.The expression level of HO-1 was measured by Western blotting.② A 3D-QSAR model was constructed using comparative molecular similarity indices analysis(CoMSIA)based on the measured HO-1 levels.The applicability domain(AD)of the model was evaluated using the leverage method.Model fitting quality and predictive ability were evaluated via the KNIME Enalos+node to verify model stability.Additionally,molecular docking was performed to validate the binding interactions between PAEs and HO-1.RESULTS ① Compared with the solvent control group,48 h of exposure to 0.062 5 mmol·L-1 PAEs(DMP,DMEP,DEHP,DnOP and DEP)significantly increased HO-1 protein expressions,while 1 mmol·L-1 PAEs(DMP,DBP,DnOP,DEP and DHXP)significantly suppressed HO-1 expressions.② The 3D-QSAR model showed a non-cross-validated coefficient(R2)of 0.996 and a cross-validated coefficient(Q2)of 0.548.All the seven PAEs in the 3D-QSAR model were within the applicability domain(AD)and passed external validation.Molecular docking results indi-cated that DBP,DnOP,DEHP and DHXP exhibited stronger binding affinities to HO-1.CONCLUSION Forty-eight hours of exposure of HepG2 cells to 1 mmol·L-1 PAEs can significantly suppress HO-1 expres-sions.The 3D-QSAR model established in this study provides a potential tool for predicting the HO-1-related toxic effects of novel PAEs.
4.Application value of needle-knife accurate fistulotomy for difficult biliary cannulation during endoscopic retrograde cholangiopancreatography
Yijun SHU ; Hao WENG ; Mingzhe WENG ; Wenjie ZHANG ; Mingning ZHAO ; Jun GU ; Xuefeng WANG
Chinese Journal of Digestive Surgery 2025;24(7):905-911
Objective:To investigate the application value of needle-knife accurate fistulo-tomy (NKAF) for difficult biliary cannulation during endoscopic retrograde cholangiopancreato-graphy (ERCP).Methods:The retrospective and descriptive study was conducted. The clinicopatho-logical data of 137 patients with difficult biliary cannulation during ERCP at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between January 2021 and December 2022 were collected. There were 51 males and 86 females, aged (69±13)years. All 137 patients received NKAF for cannulation during ERCP. Observation indicators: (1) surgical situations; (2) complications. Measurement data with normal distribution were represented as Mean± SD. Count data were repre-sented as absolute numbers. Results:(1) Surgical situations. Of 137 patients, 136 cases had succe-ssful cannulation, 1 case had failed cannulation with NKAF following unsuccessful double-guidewire technique. In the 136 successful cases, the endoscope was straightened in 42 cases, left in a long position in 37 cases, and maintained in the standard position in 57 cases. The cannulation time was (90±8)s. (2) Complications. The serum amylase at postoperative 6 hours in the 136 successful cases was (163±23)U/L. No patient developed post-ERCP pancreatitis. Of the 136 patients with successful cannulation, one case experienced post-sphincterotomy bleeding, which was observed oozing from the papillary orifice on emergency gastroscopy. The patient was successfully controlled with endoscopic clips.Conclusion:NKAF is safe and effective for difficult biliary cannulation during ERCP.
5.Experience and influencing factors of endoscopic retrograde cholangiopancreatography intubation in children
Shizhen ZHOU ; Hao WENG ; Mingzhe WENG ; Yijun SHU ; Yuanyuan YE ; Wenjie ZHANG ; Xuefeng WANG
Chinese Journal of Digestive Endoscopy 2022;39(3):203-208
Objective:To report pediatric endoscopic retrograde cholangiopancreatography (ERCP) intubation techniques and to analyze the influencing factors of pediatric ERCP in China.Methods:Retrospective analysis was performed on 90 cases of pediatric and adult ERCP operations respectively at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2016 to June 2020. The anatomic data, intubation time, and endoscopic intubation measures were reviewed. The anatomic differences in duodenal papilla between the children and adults were analyzed to find the factors affecting ERCP intubation time in children.Results:There were 88 cases of successful infantile intubation with the success rate of 97.8%, and 90 cases of successful adult intubation with the success rate of 100.0%. The intubation time in the pediatric group was 187±67 s, and that in the adult group was 247±86 s with significant difference ( t=5.220, P<0.001). The duodenal diameter of pediatric patients was 3.38±1.57 cm, and that of adult patients was 5.94±1.87 cm with significant difference ( t=9.832, P<0.001). The horizontal distance from the duodenal bulb to the papilla in pediatric patients was 2.44±1.15 cm, which was significantly shorter than 4.22±1.43 cm in adult patients ( t=9.077, P<0.001). Most duodenal papillae in children were hemispherical [flat 26.1% (23/88), hemispherical 51.1% (45/88), cylindrical 22.7% (20/88)], while most of those in the adult patients were cylindrical [flat 9.1% (8/88), hemispherical 23.9% (21/88), cylindrical 67.0% (59/88)]. The factors influencing the intubation time of ERCP in children by univariate analysis included the shape of duodenal papilla, duodenal papilla hardness, visual region, distance from junction of duodenal bulb and descending part to duodenal papilla, distance from duodenal papilla to endoscope, and degree of incising. Conclusion:Shorter and stiffer duodenal papillae in children with normal papilla orientation are associated with shorter intubation time. These indicators are favorable factors for intubation.
6.Predictive value of preoperative gastric fund volume on postoperative gastroparesis
Shizhen ZHOU ; Hao WENG ; Su LEI ; Haibin LIANG ; Lei CHEN ; Wenjie ZHANG ; Xuefeng WANG
Chinese Journal of General Surgery 2021;36(4):272-276
Objective:To study the relationship between gastric fundus size and postoperative gastroparesis and to find effective ways to prevent postoperative gastroparesis in high-risk patients.Methods:We retrospectively reviewed the clinical data of 276 gastric cancer patients undergoing radical gastrectomy from 2015 to 2016. The gastric fundus volume/total gastric volume (FV/TV) ratio was measured by computed tomography (CT) and comparative study between the gastroparesis group and the non-gastroparesis group was carried out in terms of postoperative gastroparesis. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance. Single-factor and multiple-factor analyses were performed to filter clinically significant predictive factors of gastroparesis. Then, we increased the sample size to 304 patients whose FV/TV ratio was >19.4%. The different surgical methods and perioperative management of these patients were analysed. The chi-square test and logistic regression analysis were performed to identify effective independent factors for preventing gastroparesis.Results:The FV/TV ratio in the gastroparesis group was significantly higher than that in the non-gastroparesis group ( P<0.05). A cut-off value of 19.4% was selected by ROC curve analysis, at which the FV/TV ratio had a sensitivity of 76.2% and a specificity of 53.7%. In 304 patients in the second retrospective study, the incidence of gastroparesis was 9.2%. Gastroparesis was significantly reduced in patients with residual gastric size <1/3 ( P<0.05) and early postoperative gastrointestinal decompression ( P<0.05). Conclusions:The FV/TV ratio can effectively predict the risk of postoperative gastroparesis preoperatively. Small residual stomach and early postoperative gastrointestinal decompression are effective measures to prevent gastroparesis in high-risk patients.
7.Influences of gas explosion on acute blast lung injury and time phase changes of pulmonary function in rats under real roadway environment
Xinwen DONG ; Sanqiao YAO ; Weidong WU ; Jia CAO ; Xiaogang WENG ; Lei SUN ; Juan LI ; Houcheng REN ; Wenjie REN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(2):137-142
Objective:The aims of this study were to investigate the effect of gas explosion on rats and to explore the pulmonary function alterations associated with gas explosion-induced acute blast lung injury (ABLI) in real roadway environment.Methods:In April 2018, the large coal mine gas explosion test roadway and explosion test system were used to simulate the real gas explosion roadway environment, fixed the cage and set the explosion parameters. 72 SD rats, male, SPF grade, were randomly divided into nine groups by completely random grouping method according to their body weight: control group, close range group (160 m) , and long range group (240 m) . In each group, there were wound groups (24 h group and 48h group, 8/group, total 48 in six groups) and no wound groups (8/group, total 24 in three groups) . Except for the control group, the other groups were placed in cages at different distances under anesthesia, the experiment of gas explosion was carried out by placing the rats in a position that could force the lungs. The changes of respiratory function of the rats in the non-invasive group were monitored with pulmonary function instrument at 2 h, 24 h, 48 h, 72 h and 168h after the explosion, and were killed under anesthesia 7 days later; the rats in invasive groups were anesthetized and killed at 24 h, 48 h and 168 h, respectively. Gross observation, lung wet-dry ratio and lung histopathology were performed.Results:Compared with the control group, f (respiratory frequency, f) , MV (minute ventilation, MV) , PEF (peak expiratory flow rate, PEF) , PIF (peak inspiratory flow rate, PIF) and EF50 (1/2 tidal volume expiratory flow, EF50) of rats in the close and long range groups decreased significantly after gas explosion 2 h. PAU (respiration pause, PAU) , Te (expiratory time, Te) , Ti (inspiratory time, Ti) and Tr (relaxation time, Tr) were significantly increased ( P<0.05) . After 48 h, TV (tidal volume, TV) , Penh (enhanced respiration pause, Penh) , PAU, and PIF of rats in the long range group were significantly increased ( P<0.05) . After 72 h, MV in the long range group was significantly decreased ( P<0.05) . Compared with the control group, Penh, PAU, Ti and Te were significantly decreased after 168 h in the close and long range groups, with statistical significance ( P<0.05) . At the same time, the body weight of rats in different range groups was significantly decreased ( P<0.05) . In addition, both HE staining and routine observation of lung tissues of rats in different range groups showed that gas explosion caused pulmonary edema, obviously congested pulmonary capillaries, a large number of inflammatory cells and infiltrated red blood cells. Conclusion:Gas explosion in real roadway environment can cause the change of respiratory function phase and lung tissue damage in rats, suggesting that the model of gas explosion-induced ABLI has been initially established successfully, which would provide a basis for further study on the pathogenesis of ABLI.
8.Influences of gas explosion on acute blast lung injury and time phase changes of pulmonary function in rats under real roadway environment
Xinwen DONG ; Sanqiao YAO ; Weidong WU ; Jia CAO ; Xiaogang WENG ; Lei SUN ; Juan LI ; Houcheng REN ; Wenjie REN
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(2):137-142
Objective:The aims of this study were to investigate the effect of gas explosion on rats and to explore the pulmonary function alterations associated with gas explosion-induced acute blast lung injury (ABLI) in real roadway environment.Methods:In April 2018, the large coal mine gas explosion test roadway and explosion test system were used to simulate the real gas explosion roadway environment, fixed the cage and set the explosion parameters. 72 SD rats, male, SPF grade, were randomly divided into nine groups by completely random grouping method according to their body weight: control group, close range group (160 m) , and long range group (240 m) . In each group, there were wound groups (24 h group and 48h group, 8/group, total 48 in six groups) and no wound groups (8/group, total 24 in three groups) . Except for the control group, the other groups were placed in cages at different distances under anesthesia, the experiment of gas explosion was carried out by placing the rats in a position that could force the lungs. The changes of respiratory function of the rats in the non-invasive group were monitored with pulmonary function instrument at 2 h, 24 h, 48 h, 72 h and 168h after the explosion, and were killed under anesthesia 7 days later; the rats in invasive groups were anesthetized and killed at 24 h, 48 h and 168 h, respectively. Gross observation, lung wet-dry ratio and lung histopathology were performed.Results:Compared with the control group, f (respiratory frequency, f) , MV (minute ventilation, MV) , PEF (peak expiratory flow rate, PEF) , PIF (peak inspiratory flow rate, PIF) and EF50 (1/2 tidal volume expiratory flow, EF50) of rats in the close and long range groups decreased significantly after gas explosion 2 h. PAU (respiration pause, PAU) , Te (expiratory time, Te) , Ti (inspiratory time, Ti) and Tr (relaxation time, Tr) were significantly increased ( P<0.05) . After 48 h, TV (tidal volume, TV) , Penh (enhanced respiration pause, Penh) , PAU, and PIF of rats in the long range group were significantly increased ( P<0.05) . After 72 h, MV in the long range group was significantly decreased ( P<0.05) . Compared with the control group, Penh, PAU, Ti and Te were significantly decreased after 168 h in the close and long range groups, with statistical significance ( P<0.05) . At the same time, the body weight of rats in different range groups was significantly decreased ( P<0.05) . In addition, both HE staining and routine observation of lung tissues of rats in different range groups showed that gas explosion caused pulmonary edema, obviously congested pulmonary capillaries, a large number of inflammatory cells and infiltrated red blood cells. Conclusion:Gas explosion in real roadway environment can cause the change of respiratory function phase and lung tissue damage in rats, suggesting that the model of gas explosion-induced ABLI has been initially established successfully, which would provide a basis for further study on the pathogenesis of ABLI.
9. Endoscopicretrograde cholangio-pancreatography management of long-term complications after pancreaticoduodenectomy
Wenguang WU ; Wenjie ZHANG ; Jun GU ; Mingning ZHAO ; Hao WENG ; Mingzhe WENG ; Yi ZHANG ; Chunying QU ; Leiming XU ; Yingbin LIU ; Xuefeng WANG
Chinese Journal of Surgery 2018;56(11):833-836
Objective:
To investigate the feasibility and effectiveness of endoscopicretrograde cholangio-pancreatography(ERCP)in the management of long-term complications after pancreaticoduodenectomy.
Methods:
From January 2009 to July 2018, the clinical data of 62 patients with biliary or pancreatic long-term complications after pancreatoduodenectomy were reviewed at Department of General Surgery, and the corresponding ERCP were carried out in the multi-disciplinary cooperation.There were 39 males and 24 females.The age was 56.5 years(aging from 13 to 76 years). The time of treatment was 3 months to 20 years after pancreatoduodenectomy.The long-term biliopancreatic complications after pancreatoduodenectomy included 51 cases of biliary calculi, 42 cases of bilioenteric anastomotic stenosis with proximal bile duct dilatation, and 11 cases of pancreaticointestinal anastomosis stenosis with distal pancreatic duct dilatation.All patients received conventional duodenoscopy or single-balloon enteroscopy assisted ERCP under general anesthesia.
Results:
A total of 95 ERCP were performed in 62 patients, averaging 1.5 times per case.The long-term complications of cholangiopancreatic after pancreatoduodenectomy(ERCP indications) included 56 times of bile duct stones(58.9%), 45 times of bilioenteric anastomatic stricture(47.4%), 11 times of recurrent pancreatitis(11.6%), 6 cases(6.3%) of bilioenteric anastomatic foreign body, 3 times of intrahepatic bile duct stenosis(3.2%). Among the 95 times, 82 times(86.3%) achieved endoscopic endoscopy, 76 times(80.0%) were diagnosed successfully, and 72 times(75.8%) were successfully treated with ERCP.Small intestinal perforation occurred in 1 patient undergoing duodenoscopy, and then healed by surgical repair.
Conclusion
Multi-disciplinary collaboration of ERCP is safe and effective in the treatment of long-term complications after pancreaticoduodenectomy, but the long-term effect still needs further clinical follow-up.
10.Neuroendocrine differentiation and Wilms' tumor protein-1 expression in breast mucinous carcinoma and their significance.
Jiaochen WANG ; Shouxiang WENG ; Xiaofen JIN ; Wenjie YU ; Tao ZHOU ; Meifu GAN
Journal of Zhejiang University. Medical sciences 2016;45(1):45-50
OBJECTIVETo investigate neuroendocrine differentiation and Wilms' tumor protein-1 (WT-1) expression in breast mucinous carcinoma and their clinicopathological significance.
METHODSThe clinicopathological data of 65 patients with breast mucinous carcinoma, including 31 cases of mixed mucinous carcinoma, 23 cases of hypocellular pure mucinous carcinoma and 11 cases of hypercellular pure mucinous carcinoma, admitted in Taizhou Hospital from January 2010 to June 2015 were retrospectively reviewed. The expression of neuroendocrine markers and WT-1 was detected by immunohistochemistry staining in all cases.
RESULTSThe mixed mucinous carcinomas and hypercelluar pure mucinous carcinomas had higher incidence of axillary lymph node metastasis and human epidermal recepter 2 (HER-2) positive than hypocellular pure mucinous carcinoma (all (P<0.01). However, the difference was not significant between mixed mucinous carcinomas and hypercellular pure mucinous carcinomas (all P>0.05). The expression of neuroendocrine marker was stronger in hypercellular mucinous carcinoma than that in mixed mucinous carcinoma and hypocellular mucinous carcinoma (all (P<0.05), but the difference was not statistically significant between mixed mucinous carcinoma and hypocellular pure mucinous carcinoma (P>0.05). The expression of WT-1 was weaker in mixed mucinous carcinoma than that in hypercellular and hypocellular pure mucinous carcinoma(all (P<0.05), but the difference was not statistically significant between hypercellular and hypocellular pure mucinous carcinoma (P>0.05). The mucinous carcinomas with lymph node metastasis had lower expression of neuroendocrine markers than those without lymph node metastasis ((P<0.01). The expression of WT-1 in breast mucinous carcinoma with lymph node metastasis trended lower than that in those without lymph node metastasis, but the difference was not statistically significant (P>0.05).
CONCLUSIONHypercellular pure mucinous breast carcinoma has higher rates of lymph node metastasis and HER-2 amplification than hypocellular pure mucinous carcinoma, the sub-classification of breast pure mucinous carcinoma should be considered. Neuroendocrine differentiation and WT-1 expression may be helpful in distinguishing the subtypes of breast mucinous carcinoma. Breast mucinous carcinoma with neuroendocrine differentiation trends to have less lymph node metastasis.
Adenocarcinoma, Mucinous ; classification ; diagnosis ; pathology ; Axilla ; Breast Neoplasms ; classification ; diagnosis ; pathology ; Female ; Humans ; Immunohistochemistry ; Incidence ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Neuroendocrine Tumors ; diagnosis ; pathology ; Receptor, ErbB-2 ; metabolism ; Retrospective Studies ; WT1 Proteins ; metabolism

Result Analysis
Print
Save
E-mail