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.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.
3.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.
4.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.
5.Influencing factors analysis of textbook outcome after hepatectomy for hepatolithiasis
Zixiang CHEN ; Jiangming CHEN ; Qi GUO ; Tian PU ; Xinyuan HU ; Haonan SUN ; Xiaoping GENG ; Fubao LIU
Chinese Journal of Digestive Surgery 2023;22(S1):28-33
Objective:To investigate the influencing factors for textbook outcome (TO) after hepatectomy for hepatolithiasis.Methods:The retrospective case-control study was conducted. The clinicopathological data of 216 patients with hepatolithiasis who were admitted to The First Affi-liated Hospital of Anhui Medical University from January 2015 to March 2023 were collected. There were 69 males and 147 females, aged 61(range, 22-85)years. Observation indicators: (1) treatment situations; (2) TO after hepatectomy; (3) Influencing factors for TO after hepatectomy. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers. Logistic regression models were used for univariate and multifactorial analyses. Results:(1) Treatment situations. All the 216 patients underwent hepatectomy, including 45 cases of laparoscopic hepatectomies and 171 cases of open hepatectomies, 161 cases of anatomical hepatectomies and 55 cases of non-anatomical hepatectomies. All the 216 patients underwent intraoperative choledochoscopy exploration and lithotripsy. There were 170 patients with normal Oddi sphincter function and 46 patients with Oddi sphincter dysfunction. All the 216 patients underwent biliary drainage, including 198 cases of external T-tube drainage and 18 cases of internal bile-intestinal drainage. The operation time was (226±75)minutes and volume of intraoperative blood loss was (106±82)mL. There were 29 patients with perioperative blood transfusion and 14 patients with intraoperative severe adverse events. There were 189 patients achieved immediate stone clearance. Of 183 patients with intraoperative bile cultures, 76 cases were positive for bacteria culture. (2) TO after hepatectomy. Of 216 patients, 93 cases had postoperative complications, all of which were successfully discharged after active treatment. One patient had surgery-related death within 90 days after surgery, and the cause of death was liver failure. Five patients were readmitted within 90 days after surgery, and 18 patients had postoperative stone residual. Of 216 patients, 164 cases achieved TO postoperatively and 52 cases did not achieve TO postoperatively. (3) Influencing factors for TO after hepatectomy. Results of multivariate analysis showed that cholangitis, stone distribution, surgical approaches, anatomical hepatectomy, immediate stone removal and postoperative review of choledochoscopy were independent influencing factors for TO after hepatectomy in patients with hepatolithiasis ( P<0.05). Conclusion:Cholangitis, stone distribution, surgical approaches, anatomical hepatectomy, imme-diate stone removal and postoperative review of choledochoscopy are independent influencing factors for TO after hepatectomy in patients with hepatolithiasis.
6.Current status and progress on non-surgical treatment of hepatocellular carcinoma
Zhaowen ZHANG ; Zixiang CHEN ; Jiangming CHEN ; Fubao LIU
Chinese Journal of Digestive Surgery 2023;22(S1):106-111
Primary liver cancer (PLC) is one of the most common malignant tumors with characteristics of strong invasiveness and poor prognosis. The morbidity and mortality of PLC rank among the top malignant tumors in the world. More than half of the world′s liver cancer occurs in China, which seriously threatens the health and life of Chinese people. Due to the imperceptible initial symptoms, most patients are not diagnosed until their tumors have progressed to be in advanced stage, and lose the chance for curative hepatectomy. At present, non-surgical treatment options, including interventional embolization, ablation, radiotherapy, chemotherapy, and systemic chemotherapy, play an increasingly prominent role in the comprehensive treatment of liver cancer. The authors briefly review the current status and research progress of the non-surgical treatment for liver cancer.
7.Clinical efficacy of precise hepatectomy for the treatment of recurrent unilateral hepato-lithiasis and prognostic factors analysis
Tian PU ; Jiangming CHEN ; Qi GUO ; Dong JIANG ; Zihan LI ; Fubao LIU ; Xiaoping GENG
Chinese Journal of Digestive Surgery 2022;21(2):273-280
Objective:To investigate the clinical efficacy of precise hepatectomy for the treatment of recurrent unilateral hepatolithiasis and prognostic factors.Methods:The retrospec-tive case-control study was conducted. The clinicopathological data of 166 patients with recurrent unilateral hepatolithiasis who were treated by precise hepatectomy in the First Affiliated Hospital of Anhui Medical University from January 2015 to January 2021 were collected. There were 51 males and 115 females, aged (58±12)years. Observation indicators: (1)diagnosis and classification; (2) surgical and intraoperative situations; (3) postoperative situations; (4) follow-up; (5) analysis of prognostic factors. Follow-up was conducted using the outpatient examination and telephone inter-view to detect final stone clearance or recurrence and survival of patients up to August 2021. Patients with T-tube were performed T-tube cholangiography or choledochoscopy to evaluate the final stone clearance rate at postoperative week 8. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers or percentages. Univariate and multi-variate analyses were conducted using the Logistic regression model. Results:(1) Diagnosis and classifica-tion: 166 patients were diagnosed as hepatolithiasis by preoperative imaging examination and intraoperative evaluation, including 134 cases with common bile duct stones. Of the 166 patients, 115 cases had stones located in the left lobe of liver and 51 cases had stones located in the right lobe of liver. There were 111 cases with bile pigment stones, 31 cases with cholesterol stones, 24 cases with mixed type of stones. There were 9 cases classified as Tsunoda type Ⅰ, 89 cases as Tsunoda type Ⅱ, 65 cases as Tsunoda type Ⅲ, 3 cases as Tsunoda type Ⅳ. There were 12 cases classified as type Ⅰ, 99 cases as type Ⅱ, 47 cases as type Ⅲ, 8 cases as type Ⅳ according to Japanese classification in 2001. All the 166 patients were classified as type Ⅰ based on Chinese classification. According to the classification of author team, 166 patients were classified as type Ⅱ. (2) Surgical and intra-operative situations: 119 of 166 patients had liver lobe or segment atrophy. All the 166 patients underwent precise hepatectomy combined with different methods of drainage, of which 28 cases underwent left hemihepatectomy, 11 cases underwent right hemihepatectomy, 1 case underwent liver resection of segment Ⅰ, 5 cases underwent liver resection of segment Ⅱ, 5 cases underwent liver resection of segment Ⅲ, 8 cases underwent liver resection of segment Ⅳ (left medial lobe), 3 cases underwent liver resection of segment Ⅴ, 2 cases underwent liver resection of segment Ⅵ, 2 cases underwent liver resection of segment Ⅷ, 68 cases underwent liver resection of segment Ⅱ and Ⅲ (left lateral lobe), 3 cases underwent liver resection of segment Ⅴ and Ⅵ, 6 cases underwent liver resection of segment Ⅴ and Ⅷ (right anterior lobe), 21 cases underwent liver resection of segment Ⅵ and Ⅶ (right posterior lobe), 1 case underwent liver resection of segment Ⅱ, Ⅲ and Ⅳa, 1 case underwent liver resection of segment Ⅴ, Ⅵ and Ⅶ, 1 case underwent liver resection of segment Ⅰ, Ⅱ, Ⅲ and Ⅳ. For biliary drainage methods of 166 patients, 120 patients received T-tube external drainage, 23 cases received choledochojejunostomy, 23 cases received choledochojejunostomy combined with T-tube external drainage. The original cholangiojejunal anastomotic stenosis was found and reconstructed in 10 patients. The operation time was (258±87)minutes and intraopera-tive blood transfusion rate was 16.87%(28/166) of 166 patients. All the 166 patients underwent fiber choledochoscopy, showing 77 cases with normal function of Oddi sphincter, 38 cases with disorder, 40 cases with dysfunction. There were 11 patients undergoing choledochojejunostomy who were not evaluate the function of Oddi sphincter. There were 21.69%(36/166)of patients with intra-hepatic biliary stricture. One hundred and forty-nine of 166 patients were conducted bile culture, showing the positive rate as 75.17%(112/149). There were 22 cases cultured multiple kinds of bacteria. The most common bacterium was Escherichia coli (43 cases), followed by Pseudomonas aeruginosa (12 cases), Klebsiella pneumoniae (9 cases), Klebsiella oxytoca (7 cases), Enterococcus faecium (7 cases). (3) Postoperative situations. The postoperative complication rate of 166 patients was 16.87%(28/166). In the 8 patients with serious complications of Clavien-Dindo grade Ⅲ, 6 cases were performed thoracocentesis or abdominocentesis for effusion, 1 case was stopped bleeding under gastroscopy for stress ulcerbleeding, 1 case was performed surgery for adhesive intestinal obstruction. Two patients with septic shock of Clavien-Dindo grade Ⅳ were converted to intensive care unit for treatment and discharged after recovery. There were 13 patients with biliary leakage, 10 patients with pulmonary infection, 6 cases with incision infection, which were improved after conservative treatments. There was no perioperative death. The instant stone clearance rate of 166 patients was 81.93%(136/166). The duration of postoperative hospital stay of 166 patients was (11±6)days. (4) Follow-up: 166 patients were followed up for (37±17)months. The final stone clearance rate and stone recurrence rate of 166 patients were 94.58%(157/166) and 16.87%(28/166), respectively. According to Terblanche classification of prognosis, there were 91, 36, 25, 14 cases of grade Ⅰ, Ⅱ, Ⅲ, Ⅳ in 166 patients, respectively. Five of the 166 patients underwent intrahepatic secondary malignancy in which 4 cases died. (5) Analysis of prognostic factors: results of univariate analysis showed that biliary culture, the number of previous surgeries, immediate stone clearance, final stone clearance were related factors affecting the prognosis of precise hepatectomy in patients with recurrent unilateral hepatolithiasis ( odds ratio=2.29, 7.48, 2.69, 4.52, 95% confidence interval as 1.09?4.85, 2.80?19.93, 1.16?6.25, 1.15?17.77, P<0.05). Results of multivariate analysis showed that the number of previous surgeries ≥3 was an independent risk factor affecting the prognosis of precise hepatectomy in patients with recurrent unilateral hepato-lithiasis ( odds ratio=6.05, 95% confidence interval as 2.20?16.62, P<0.05). Conclusions:Precise hepatectomy is safe and effective for the treatment of patients with recurrent unilateral hepato-lithiasis. The number of previous surgeries ≥3 is an independent risk factor affecting the prognosis of precise hepatectomy in patients with recurren t unilateral hepatolithiasis.
8.Surgical diagnosis and treatment of adult huge undifferentiated embryonal sarcoma of the liver
Tian PU ; Jiangming CHEN ; Qi GUO ; Lijie YANG ; Xiaoping GENG ; Fubao LIU
Chinese Journal of Surgery 2021;59(10):848-853
Objective:To investigate the clinical characteristics of adult undifferentiated embryonal sarcoma of the liver (UESL).Methods:A retrospective analysis was performed on the clinical data of 5 patients with UESL who underwent surgical resection and were pathologically confirmed from January 2005 to December 2020 at the First and the Second Affiliated Hospital of Anhui Medical University. All the patients were female aged from 49 to 77 years old. Preoperative CT showed a solid cystic mass with low density and a slight density of cord like septum. Imaging findings were misdiagnosed as hepatocellular carcinoma or cystadenocarcinoma. CA125 was higher in 3 patients,and AFP in all patients was normal.Results:All patients were treated by surgery. The mean diameter of tumor was 20.2 cm (range:15.0 to 30.0 cm). All five patients had vimentin expression in immunohistochemistry. Three cases underwent complete resection of the tumor and achieved R0 resection,2 of them had tumor free survival until the end of the follow-up (89 and 55 months),the other 1 case died from renal cell carcinoma 158 months later. The remaining 2 cases were radically resected,but the tumors were ruptured during operation,and relapsed after 2 months and 19 months respectively. The overall survival was 3 and 26 months respectively.Conclusions:Radical hepatectomy is the first choice for treatment of UESL. Intraoperative tumor rupture should be avoided and implant metastasis is a major factor affecting the prognosis of UESL.
9.Surgical diagnosis and treatment of adult huge undifferentiated embryonal sarcoma of the liver
Tian PU ; Jiangming CHEN ; Qi GUO ; Lijie YANG ; Xiaoping GENG ; Fubao LIU
Chinese Journal of Surgery 2021;59(10):848-853
Objective:To investigate the clinical characteristics of adult undifferentiated embryonal sarcoma of the liver (UESL).Methods:A retrospective analysis was performed on the clinical data of 5 patients with UESL who underwent surgical resection and were pathologically confirmed from January 2005 to December 2020 at the First and the Second Affiliated Hospital of Anhui Medical University. All the patients were female aged from 49 to 77 years old. Preoperative CT showed a solid cystic mass with low density and a slight density of cord like septum. Imaging findings were misdiagnosed as hepatocellular carcinoma or cystadenocarcinoma. CA125 was higher in 3 patients,and AFP in all patients was normal.Results:All patients were treated by surgery. The mean diameter of tumor was 20.2 cm (range:15.0 to 30.0 cm). All five patients had vimentin expression in immunohistochemistry. Three cases underwent complete resection of the tumor and achieved R0 resection,2 of them had tumor free survival until the end of the follow-up (89 and 55 months),the other 1 case died from renal cell carcinoma 158 months later. The remaining 2 cases were radically resected,but the tumors were ruptured during operation,and relapsed after 2 months and 19 months respectively. The overall survival was 3 and 26 months respectively.Conclusions:Radical hepatectomy is the first choice for treatment of UESL. Intraoperative tumor rupture should be avoided and implant metastasis is a major factor affecting the prognosis of UESL.


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