1.Knocking down HMGN2 can inhibit the proliferation, migration, and invasion of lung adenocarcinoma cells
Zhi Chen ; Xiao Zhu ; Fubao Xing ; Chao Song ; Yang Geng ; Wei Wang ; Lei Zhang
Acta Universitatis Medicinalis Anhui 2025;60(3):472-479, 487
Objective :
To investigate the effects and underlying mechanisms of high mobility group nucleosome-binding domain protein 2(HMGN2) on lung adenocarcinoma cells.
Methods :
This work first analyzed the association between HMGN2 and lung adenocarcinoma tissues using The Cancer Genome Atlas(TCGA) database. Lung adenocarcinoma tissues and adjacent normal tissues were collected to compare the differential expression levels of HMGN2. The expression of HMGN2 mRNA in lung adenocarcinoma cell lines A549 and NC-H1299 were detected by qRT-PCR and Western blot. HMGN2 expression was knocked down using si-RNA technology, with the control group transfected with an equivalent amount of NC-siRNA, and the si-RNA group transfected with si-HMGN2. Stable transfected cell lines were established based on si-RNA knockdown efficiency. The effects of HMGN2 knockdown on the growth, movement, and spread of lung adenocarcinoma cells were assessed using CCK-8, Transwell assays, scratch assays, colony formation assays, and EdU assays. Transcriptome sequencing analysis revealed pathways related to tumorigenesis associated with HMGN2. The relative expression levels of MAPK pathway proteins after HMGN2 knockdown were detected by Western blot.
Results :
HMGN2 mRNA expression was significantly elevated in lung cancer tissues and lung adenocarcinoma cell lines(P<0.05). After HMGN2 knockdown, cell proliferation, migration, and invasion were significantly reduced(P<0.05), and the phosphorylation levels of the MAPK signaling pathway markedly decreased(P<0.05).
Conclusion
HMGN2 enhances the proliferation, migration, and invasion of lung adenocarcinoma cells, and its mechanism may be closely related to the activation of the MAPK signaling pathwayviaphosphorylation.
2.Study on preoperative administration time and dose of indocyanine green for extrahepatic biliary tract imaging in the laparoscopic cholecystectomy
Jiangming CHEN ; Dong JIANG ; Kangwei FANG ; Fubao LIU
Chinese Journal of Digestive Surgery 2025;24(7):882-889
Objective:To investigate the preoperative administration time and dose of indo-cyanine green (ICG) for extrahepatic biliary tract imaging in the laparoscopic cholecystectomy (LC).Methods:The retrospective study was conducted. The clinical data of 252 patients with gallbladder diseases who were admitted to The Affiliated Hospital of Anhui Medical University from December 2022 to December 2024 were collected. There were 137 males and 115 females, aged (45±4)years. All patients underwent LC after injection of 1.25 mg or 2.50 mg ICG, with ICG fluore-scence navigation during the operation. Observation indicators: (1) effective fluorescence imaging during surgery; (2) the ratio of fluorescence intensity between gallbladder duct and liver, and the ratio of fluorescence intensity between common bile duct and liver; (3) the imaging effect of extra-hepatic biliary tract. Comparison of measurement data with skewed distribution among groups was conducted using the Kruskal-Wallis H test, and the Bonferroni method was used for pairwise com-parison. The consistency evaluation was conducted using the Kendall test. Results:(1) Effective fluorescence imaging during surgery. The Kendall coefficient index was 0.83, indicating high consis-tency in evaluation of fluorescence imaging of extrahepatic biliary tract between doctors. The effective fluorescent imaging sites during surgery were located in the liver, cystic duct, common bile duct, cystic duct-common bile duct junction, hepatic duct, and gallbladder. The intraoperative effective fluorescence imaging of patients who received intravenous injection of 1.25 mg and 2.50 mg ICG before surgery showed that as the interval between ICG injection and surgery increased, the proportion of fluorescence imaging in the liver and gallbladder gradually decreased. The proportion of fluorescence imaging in the gallbladder duct, common bile duct, cystic duct-common bile duct junction, common hepatic duct showed a trend of first increasing and then decreasing. (2) The ratio of fluorescence intensity between gallbladder duct and liver, and the ratio of fluorescence intensity between common bile duct and liver. Results of Kruskal Wallis H test showed that there were significant differences in the fluorescence intensity ratios of gallbladder duct to liver and the fluorescence intensity ratio of common bile duct to liver among patients who received intravenous injection of 1.25 mg ICG at different time intervals to surgery ( H=73.22, 77.17, P<0.05). Results of pairwise comparison showed that there were significant differences in the fluorescence intensity ratio of gallbladder duct to liver and the fluorescence intensity ratio of common bile duct to liver between patients who received intravenous ICG injection 4.0-<6.0 hours before surgery and those who received ICG injection <0.5 hours, 0.5-<2.0 hours, 2.0-<4.0 hours, 6.0-<8.0 hours, 8.0-<10.0 hours, and 10.0-<12.0 hours before surgery, respectively ( P<0.002). There were significant differences in the fluorescence intensity ratio of gallbladder duct to liver and the fluorescence intensity ratio of common bile duct to liver among patients who received intravenous injection of 2.50 mg ICG at different time intervals to surgery ( H=127.06, 126.39, P<0.05). Results of pairwise comparison showed there were significant differences in the fluorescence intensity ratio of gall-bladder duct to liver and the fluorescence intensity ratio of common bile duct to liver between patients who received ICG injection 8.0-<10.0 hours before surgery and those who received ICG injection <0.5 hours, 0.5-<2.0 hours, 2.0-<4.0 hours, 4.0-<6.0 hours, 6.0-<8.0 hours, 12.0-<14.0 hours, and 14.0-<16.0 hours before surgery ( P<0.001). (3) The imaging effect of extrahepatic biliary tract. Among 102 patients who received preoperative intravenous injection of 1.25 mg ICG, the number of patients with grade A extrahepatic biliary system imaging increased and then decreased as the interval time extending, reaching a peak at 4.0-<6.0 hours. Among 150 patients who received preoperative intravenous injection of 2.50 mg ICG, the number of patients with grade A extrahepatic biliary tract imaging increased and then decreased as the interval time extending, reaching a peak at 8.0-<10.0 hours. Conclusion:Prolonging the time interval between ICG administration and surgery can effectively reduce the fluorescence intensity of the liver background, thereby increasing the fluorescence intensity ratio of gallbladder duct to liver and common bile duct to liver to obtain the best development effect. Intravenous injection of 1.25 mg ICG 4.0-<6.0 hours before surgery or 2.50 mg ICG 8.0-<10.0 hours before surgery provide better results for intraoperative extrahepatic biliary tract imaging.
3.Construction of a preoperative prediction model for post-hepatectomy liver failure in patients with large hepatocellular carcinoma
Zhaowen ZHANG ; Xinyuan HU ; Zixiang CHEN ; Jiangming CHEN ; Xiaoping GENG ; Fubao LIU
Chinese Journal of General Surgery 2025;34(7):1390-1400
Background and Aims:Hepatocellular carcinoma(HCC)is the most prevalent type of liver malignancy,accounting for 80%of all primary liver cancer cases.Partial hepatectomy is widely considered to be the treatment of choice for HCC.However,post-hepatectomy liver failure(PHLF)is the most serious complication and the leading cause of perioperative death.Therefore,an accurate assessment of the risk of PHLF is particularly critical.Patients with large hepatocellular carcinoma have larger tumors(tumor diameter≥5 cm)and more resected liver tissue,and are more likely to develop PHLF.Previous studies have used various methods to assess the risk of PHLF,including liver function,Child-Pugh classification,model for end-stage liver disease,albumin-bilirubin(ALBI),and aspartate aminotransferase-to-platelet ratio index score.However,no model has been developed for data on hepatectomy for large HCC.Therefore,this study aims to analyze the risk factors of PHLF in HCC patients with large tumor and to construct a preoperative nomogram prediction model to guide and optimize clinical decision-making.Methods:The clinical data of 927 patients with large liver cancer who underwent radical hepatectomy in the First Affiliated Hospital of Anhui Medical University(721 cases,training cohort)and the Second Affiliated Hospital of Anhui Medical University(206 cases,validation cohort)from January 2018 to June 2023 were retrospectively collected.The patients'baseline data,laboratory examination,imaging data,and surgical information were collected.Univariate analysis combined with multivariate analysis was used to screen out the independent risk factors for inducing PHLF,and binary Logistic regression was used to construct a prediction model for PHLF.ROC,calibration,and clinical decision curves verified the model's performance.Results:There were no significant differences in all preoperative data between the training and validation cohorts(P>0.05).Grade B or C PHLF occurred in 192 of 927 patients(20.7%),including 8 patients with grade C PHLF.Univariate and multivariate Logistic regression analyses were used to determine the independent risk factors of PHLF,including tumor diameter,ALBI score,liver cirrhosis,vascular tumor thrombus,and intraoperative blood loss.These factors were included in the Logistic regression analysis,and a nomogram model was constructed to predict PHLF.The nomogram model was validated,and the C-index of the nomogram was 0.757.The ROC curve analysis of the prediction probability of the model showed that the AUC of the training set was 0.757(95%CI=0.703-0.811),and the AUC of the validation set was 0.779(95%CI=0.702-0.863).The validation showed that the model had good predictive ability.Conclusions:Tumor diameter,ALBI score,liver cirrhosis,vascular tumor thrombus,and intraoperative blood loss are independent risk factors for PHLF.The nomogram prediction model constructed in this study can accurately assess the risk of preoperative PHLF,which is helpful for better clinical management,reducing the occurrence of PHLF,and improving the postoperative prognosis of patients.
4.Study on preoperative administration time and dose of indocyanine green for extrahepatic biliary tract imaging in the laparoscopic cholecystectomy
Jiangming CHEN ; Dong JIANG ; Kangwei FANG ; Fubao LIU
Chinese Journal of Digestive Surgery 2025;24(7):882-889
Objective:To investigate the preoperative administration time and dose of indo-cyanine green (ICG) for extrahepatic biliary tract imaging in the laparoscopic cholecystectomy (LC).Methods:The retrospective study was conducted. The clinical data of 252 patients with gallbladder diseases who were admitted to The Affiliated Hospital of Anhui Medical University from December 2022 to December 2024 were collected. There were 137 males and 115 females, aged (45±4)years. All patients underwent LC after injection of 1.25 mg or 2.50 mg ICG, with ICG fluore-scence navigation during the operation. Observation indicators: (1) effective fluorescence imaging during surgery; (2) the ratio of fluorescence intensity between gallbladder duct and liver, and the ratio of fluorescence intensity between common bile duct and liver; (3) the imaging effect of extra-hepatic biliary tract. Comparison of measurement data with skewed distribution among groups was conducted using the Kruskal-Wallis H test, and the Bonferroni method was used for pairwise com-parison. The consistency evaluation was conducted using the Kendall test. Results:(1) Effective fluorescence imaging during surgery. The Kendall coefficient index was 0.83, indicating high consis-tency in evaluation of fluorescence imaging of extrahepatic biliary tract between doctors. The effective fluorescent imaging sites during surgery were located in the liver, cystic duct, common bile duct, cystic duct-common bile duct junction, hepatic duct, and gallbladder. The intraoperative effective fluorescence imaging of patients who received intravenous injection of 1.25 mg and 2.50 mg ICG before surgery showed that as the interval between ICG injection and surgery increased, the proportion of fluorescence imaging in the liver and gallbladder gradually decreased. The proportion of fluorescence imaging in the gallbladder duct, common bile duct, cystic duct-common bile duct junction, common hepatic duct showed a trend of first increasing and then decreasing. (2) The ratio of fluorescence intensity between gallbladder duct and liver, and the ratio of fluorescence intensity between common bile duct and liver. Results of Kruskal Wallis H test showed that there were significant differences in the fluorescence intensity ratios of gallbladder duct to liver and the fluorescence intensity ratio of common bile duct to liver among patients who received intravenous injection of 1.25 mg ICG at different time intervals to surgery ( H=73.22, 77.17, P<0.05). Results of pairwise comparison showed that there were significant differences in the fluorescence intensity ratio of gallbladder duct to liver and the fluorescence intensity ratio of common bile duct to liver between patients who received intravenous ICG injection 4.0-<6.0 hours before surgery and those who received ICG injection <0.5 hours, 0.5-<2.0 hours, 2.0-<4.0 hours, 6.0-<8.0 hours, 8.0-<10.0 hours, and 10.0-<12.0 hours before surgery, respectively ( P<0.002). There were significant differences in the fluorescence intensity ratio of gallbladder duct to liver and the fluorescence intensity ratio of common bile duct to liver among patients who received intravenous injection of 2.50 mg ICG at different time intervals to surgery ( H=127.06, 126.39, P<0.05). Results of pairwise comparison showed there were significant differences in the fluorescence intensity ratio of gall-bladder duct to liver and the fluorescence intensity ratio of common bile duct to liver between patients who received ICG injection 8.0-<10.0 hours before surgery and those who received ICG injection <0.5 hours, 0.5-<2.0 hours, 2.0-<4.0 hours, 4.0-<6.0 hours, 6.0-<8.0 hours, 12.0-<14.0 hours, and 14.0-<16.0 hours before surgery ( P<0.001). (3) The imaging effect of extrahepatic biliary tract. Among 102 patients who received preoperative intravenous injection of 1.25 mg ICG, the number of patients with grade A extrahepatic biliary system imaging increased and then decreased as the interval time extending, reaching a peak at 4.0-<6.0 hours. Among 150 patients who received preoperative intravenous injection of 2.50 mg ICG, the number of patients with grade A extrahepatic biliary tract imaging increased and then decreased as the interval time extending, reaching a peak at 8.0-<10.0 hours. Conclusion:Prolonging the time interval between ICG administration and surgery can effectively reduce the fluorescence intensity of the liver background, thereby increasing the fluorescence intensity ratio of gallbladder duct to liver and common bile duct to liver to obtain the best development effect. Intravenous injection of 1.25 mg ICG 4.0-<6.0 hours before surgery or 2.50 mg ICG 8.0-<10.0 hours before surgery provide better results for intraoperative extrahepatic biliary tract imaging.
5.Construction of a preoperative prediction model for post-hepatectomy liver failure in patients with large hepatocellular carcinoma
Zhaowen ZHANG ; Xinyuan HU ; Zixiang CHEN ; Jiangming CHEN ; Xiaoping GENG ; Fubao LIU
Chinese Journal of General Surgery 2025;34(7):1390-1400
Background and Aims:Hepatocellular carcinoma(HCC)is the most prevalent type of liver malignancy,accounting for 80%of all primary liver cancer cases.Partial hepatectomy is widely considered to be the treatment of choice for HCC.However,post-hepatectomy liver failure(PHLF)is the most serious complication and the leading cause of perioperative death.Therefore,an accurate assessment of the risk of PHLF is particularly critical.Patients with large hepatocellular carcinoma have larger tumors(tumor diameter≥5 cm)and more resected liver tissue,and are more likely to develop PHLF.Previous studies have used various methods to assess the risk of PHLF,including liver function,Child-Pugh classification,model for end-stage liver disease,albumin-bilirubin(ALBI),and aspartate aminotransferase-to-platelet ratio index score.However,no model has been developed for data on hepatectomy for large HCC.Therefore,this study aims to analyze the risk factors of PHLF in HCC patients with large tumor and to construct a preoperative nomogram prediction model to guide and optimize clinical decision-making.Methods:The clinical data of 927 patients with large liver cancer who underwent radical hepatectomy in the First Affiliated Hospital of Anhui Medical University(721 cases,training cohort)and the Second Affiliated Hospital of Anhui Medical University(206 cases,validation cohort)from January 2018 to June 2023 were retrospectively collected.The patients'baseline data,laboratory examination,imaging data,and surgical information were collected.Univariate analysis combined with multivariate analysis was used to screen out the independent risk factors for inducing PHLF,and binary Logistic regression was used to construct a prediction model for PHLF.ROC,calibration,and clinical decision curves verified the model's performance.Results:There were no significant differences in all preoperative data between the training and validation cohorts(P>0.05).Grade B or C PHLF occurred in 192 of 927 patients(20.7%),including 8 patients with grade C PHLF.Univariate and multivariate Logistic regression analyses were used to determine the independent risk factors of PHLF,including tumor diameter,ALBI score,liver cirrhosis,vascular tumor thrombus,and intraoperative blood loss.These factors were included in the Logistic regression analysis,and a nomogram model was constructed to predict PHLF.The nomogram model was validated,and the C-index of the nomogram was 0.757.The ROC curve analysis of the prediction probability of the model showed that the AUC of the training set was 0.757(95%CI=0.703-0.811),and the AUC of the validation set was 0.779(95%CI=0.702-0.863).The validation showed that the model had good predictive ability.Conclusions:Tumor diameter,ALBI score,liver cirrhosis,vascular tumor thrombus,and intraoperative blood loss are independent risk factors for PHLF.The nomogram prediction model constructed in this study can accurately assess the risk of preoperative PHLF,which is helpful for better clinical management,reducing the occurrence of PHLF,and improving the postoperative prognosis of patients.
6.Mechanisms underlying internal heat-type acupuncture in the treatment of steroid-induced osteonecrosis of the femoral head in rabbits
Liangchen MA ; Fubao TIAN ; Yujuan XU ; Xinbao TIAN ; Ying TAO ; Mengying CHEN ; Jiawei LIAN ; Ruizhu LIN ; Ning ZHU
Chinese Journal of Tissue Engineering Research 2024;28(27):4353-4359
BACKGROUND:Internal heat-type acupuncture therapy is a new treatment technique that combines acupuncture therapy with hyperthermia.It has good clinical effects on steroid-induced osteonecrosis of the femoral head,but the mechanism of action is still not fully clear. OBJECTIVE:To explore the possible mechanism of internal heat-type acupuncture therapy in treating steroid-induced osteonecrosis of the femoral head in rabbits. METHODS:Thirty-two New Zealand rabbits were randomly divided into blank group,model group,internal heat-type acupuncture group and shock wave group using a random number table method,with 8 rabbits in each group.The model group,internal heat-type acupuncture group and shock wave group were modeled using methylprednisolone sodium succinate combined with Escherichia coli endotoxin.The internal heat-type acupuncture group received an internal heat-type acupuncture intervention on the buttocks of rabbits,once a week,for 20 minutes each time.The shock wave group received shock wave intervention on the buttocks of rabbits,once a week,with 2 000 beats per session.The blank group and model group were not given any treatment.After 4 weeks of intervention,blood samples and bilateral femoral head samples were collected from experimental rabbits.The levels of tumor necrosis factor-α and interleukin-6 in serum were detected by ELISA;the histomorphology of the femoral head was observed using hematoxylin-eosin staining and the rate of empty lacunae was calculated;the protein expressions of matrix metalloproteinase 2,matrix metalloproteinase 9,matrix metalloproteinase tissue inhibitor 1,and matrix metalloproteinase tissue inhibitor 2 were detected by immunohistochemistry and western blot. RESULTS AND CONCLUSION:Compared with the blank group,the model rabbits showed reduced food intake,mental fatigue,and decreased activity;compared with the model group,the above performance of the experimental rabbits was significantly improved after internal heat-type acupuncture and shock wave treatment.Compared with the blank group,the histomorphology of the femoral head in the model group deteriorated significantly and the rate of empty bone lacuna increased(P<0.001),while the histomorphology of the femoral head in the internal heat-type acupuncture group and shock wave group was significantly improved compared with the model group,and the rate of empty bone lacuna was reduced(P<0.001).The serum levels of tumor necrosis factor-α and interleukin-6 in the model group were significantly higher than those in the blank group(P<0.05),while the serum levels of tumor necrosis factor-α and interleukin-6 in the internal heat-type acupuncture group and the shock wave group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 in the femoral head of the model group were significantly increased,while the expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly decreased(P<0.001);compared with the model group,the protein expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 were significantly decreased,while the protein expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly increased in the internal heat-type acupuncture group and the shock wave group(P<0.001).Overall,these findings indicate that internal heat-type acupuncture may promote the repair of the necrotic femoral head by regulating the levels of matrix metalloproteinases/matrix metalloproteinase tissue inhibitors and serum inflammatory factors,thus treating early steroid-induced osteonecrosis of the femoral head.
7.Applications and challenges of pathomics technique in the management of hepatocellular carcinoma
Zixiang CHEN ; Jiangming CHEN ; Xiaoping GENG ; Fubao LIU
Chinese Journal of Surgery 2024;62(7):665-670
The incidence and mortality rate of hepatocellular carcinoma rank among the top of all cancer types,seriously threatening the life and health of human beings. In recent years,the rapid development of artificial intelligence and the deepening of the concept of precision medicine have led to a boom in interdisciplinary research. Pathomics,as an emerging omics technology driven by artificial intelligence,can mine massive information from high-resolution whole slide images,and shows broad application prospects in the diagnosis,treatment and prognosis assessment of hepatocellular carcinoma. However, pathomics research in hepatocellular carcinoma is still in its infancy, and its research patterns and clinical applications still face several controversies and challenges, including data security, ethics, and “black box” issues. Future research should focus on conducting prospective studies, integrating multimodal data, improving computational technologies, and establishing professional standards to promote the high-quality development of pathomics technology in both clinical and basic research of hepatocellular carcinoma.
8.Applications and challenges of pathomics technique in the management of hepatocellular carcinoma
Zixiang CHEN ; Jiangming CHEN ; Xiaoping GENG ; Fubao LIU
Chinese Journal of Surgery 2024;62(7):665-670
The incidence and mortality rate of hepatocellular carcinoma rank among the top of all cancer types,seriously threatening the life and health of human beings. In recent years,the rapid development of artificial intelligence and the deepening of the concept of precision medicine have led to a boom in interdisciplinary research. Pathomics,as an emerging omics technology driven by artificial intelligence,can mine massive information from high-resolution whole slide images,and shows broad application prospects in the diagnosis,treatment and prognosis assessment of hepatocellular carcinoma. However, pathomics research in hepatocellular carcinoma is still in its infancy, and its research patterns and clinical applications still face several controversies and challenges, including data security, ethics, and “black box” issues. Future research should focus on conducting prospective studies, integrating multimodal data, improving computational technologies, and establishing professional standards to promote the high-quality development of pathomics technology in both clinical and basic research of hepatocellular carcinoma.
9.Application and prospect of artificial intelligence in the whole-process management of pancreatic cancer
Tan LIANG ; Zixiang CHEN ; Jiangming CHEN ; Xiaoping GENG ; Fubao LIU
Chinese Journal of Digestive Surgery 2024;23(11):1459-1464
Pancreatic cancer is a highly malignant cancer with low survival rate. Early diagnosis, early treatment and early recurrence intervention are the most important keys to improve overall prognosis of pancreatic cancer. With the rapid development of artificial intelligence, it is an inevitable trend to apply it to the diagnosis and treatment of pancreatic cancer to achieve precision medicine for patients. By combining with clinical data, medical images and molecular biology, artifi-cial intelligence has shown broad application prospects in the whole-process management of pancreatic cancer. The authors briefly review the application status and problems of artificial intelligence in the diagnosis and treatment of pancreatic cancer, and discuss its future development direction.
10.Application and prospect of artificial intelligence in the whole-process management of pancreatic cancer
Tan LIANG ; Zixiang CHEN ; Jiangming CHEN ; Xiaoping GENG ; Fubao LIU
Chinese Journal of Digestive Surgery 2024;23(11):1459-1464
Pancreatic cancer is a highly malignant cancer with low survival rate. Early diagnosis, early treatment and early recurrence intervention are the most important keys to improve overall prognosis of pancreatic cancer. With the rapid development of artificial intelligence, it is an inevitable trend to apply it to the diagnosis and treatment of pancreatic cancer to achieve precision medicine for patients. By combining with clinical data, medical images and molecular biology, artifi-cial intelligence has shown broad application prospects in the whole-process management of pancreatic cancer. The authors briefly review the application status and problems of artificial intelligence in the diagnosis and treatment of pancreatic cancer, and discuss its future development direction.


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