1.Association of single nucleotide polymorphisms of miRNA-146a, miRNA-196a2 and miRNA-499 with genetic susceptibility in hepatocellular carcinoma
Lihong ZHANG ; Guangcai XU ; Guodong ZHANG ; Peijian ZHANG ; Lide TAO
Cancer Research and Clinic 2021;33(2):93-98
Objective:To explore the association of miRNA-146a (miR-146a), miRNA-196a2 (miR-196a2), and miRNA-499 (miR-499) single nucleotide polymorphisms with genetic susceptibility in hepatocellular carcinoma.Methods:A case-control study was designed. A total of 175 patients (hepatocellular carcinoma group) in Affiliated Hospital of Yangzhou University from April 2015 to March 2019 and 302 healthy people undergoing physical examination during the same period (the control group) were selected. The genotype distribution of miR-146a, miR-196a2 and miR-499 in the peripheral blood of the two groups were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression model was used to analyze the association of 3 genotypes of miRNA, genotypes of hepatitis virus infectors with genetic susceptibility in hepatocellular carcinoma. The relationship between miR-146a gene polymorphism and demography factor as well as the clinical characteristics was also analyzed by using Spearman correlation analysis.Results:In hepatocellular carcinoma group, miR-146a single nucleotide polymorphism of CC, CG, GG site genotypes had 52 (29.7%) cases, 86 (49.1%) cases, 37 (21.1%) cases, respectively; in the control group, the corresponding genotypes had 137 (45.4%) cases, 135 (44.7%) cases and 30 (9.9%) cases, respectively, and the difference in genotype distribution of both groups was statistically significant ( χ2 = 17.23, P < 0.05). There were no statistical differences in genotype distribution of miR-196a2 and miR-499 ( χ2 = 0.51, P = 0.776; χ2 = 0.05, P = 0.976). Single factor logistic regression analysis showed that in the co-dominant model of miR-146a genotype, genotypes of CG ( OR = 1.96, 95% CI 1.13-3.41, P = 0.017) and GG ( OR = 3.30, 95% CI 1.85-5.89, P<0.01) had elevated risk of hepatocellular carcinoma compared with CC genotype. In the dominant model, the risk of hepatocellular carcinoma in CG+GG genotypes was increased compared with that in CC genotype ( OR=1.97, 95% CI 1.33-2.93, P = 0.001); in the recessive model, the risk of hepatocellular carcinoma in GG genotype was increased compared with that in CG+ GG genotype ( OR=2.43, 95% CI 1.44-4.11, P = 0.001). Single factor logistic regression analysis showed that there was no significant difference in the risk of hepatocellular carcinoma in the co-dominant, dominant and recessive models between miR-196a2 and miR-499 genotypes (all P > 0.05). For hepatocellular carcinoma patients with positive hepatitis B virus (HBV), CG genotype had a 2.02-fold (95% CI 1.06-5.07) risk of hepatocellular carcinoma compared with CC genotype, and GG genotype had a 3.12-fold (95% CI 1.66-10.07) risk of hepatocellular carcinoma compared with CC genotype; CG+GG genotype had a 1.91-fold (95% CI 1.85-3.38) compared with CC genotype, GG genotype had a 1.54-fold (95% CI 1.15-6.08) compared with CG+GG genotype. The increasing risk of hepatocellular carcinoma by miR-146a gene polymorphisms was not found in hepatocellular carcinoma patients with hepatitis C virus (HCV) infection or without HBV and HCV infection. Spearman correlation analysis showed that miR-146a gene polymorphisms was not related with age, gender, smoking, drinking, family history of cancer, alanine transaminase and aspartate aminotransferase (all P>0.05). Conclusions:GG and CG genotypes of miR-146a increase the risk of genetic susceptibility in hepatocellular carcinoma, especially for patients with HBV infection. miR-196a2 and miR-499 single nucleotide polymorphisms don't increase the risk of hepatocellular carcinoma.
2.Research on the pancreatic injury after autologous liver transplantation in rats
Yong LI ; Peijian ZHANG ; Jie LANG ; Min FENG ; Cheng JIN ; Bin ZHOU ; Lide TAO ; Xinyan LIU
Chinese Journal of Digestive Surgery 2009;8(5):364-366
Objective To investigate the causes of pancreatic injury after autologous liver transplantation in rats. Methods Forty-two SD rats were randomly divided into post autologons liver transplantation 1-hour group, 6-hour group, 12-hour group, 24-hour group, 48-hour group, 72-hour group and sham group (6 rats per group). The plasma concentrations of amylase and lipase were measured to assess pancreatic exocrine function. The histomorphological changes of pancreatic tissue were studied under optical and electron microscopes. All data were analyzed via one-way ANOVA. Results The plasma concentrations of amylase and lipnse in post autologous liver transplantation 1-hour group were significantly higher than those in sham group, and they gradually increased as time passed by. The plasma concentrations of amylase and lipase reached peak at hour 48, after which they decreased gradually. There was a significant difference in the plasma concentration of amylase and lipase among the 7 groups (F = 538.622,489.417, P < 0.05). Acute edematous pancreatitis was observed 1 hour after autolognus liver transplantation, and acute hemorrhagic necrotic pancreatitis was observed 6 hours after transplantation. The degree of injury reached a peak 48 hours after transplantation. The number of mitochondria was increased, and endoplasmic reticulum and Golgi apparatus were swollen 1 hour after transplantation, and the area, perimeter, specific surface area and mean gray value of mitochondria were (312±40) mm~2, (80.3±3.8)mm, 0.332±0.039 and 113±11, respectively. As time passed by, the injury of the pancreatic cells was aggravated and autophagosomes were observed. The injury was most severe 48 hours after transplantation, and the area, perimeter, specific surface area and mean gray value of mitochondria were (466±7) mm~2, (108.8±3.7) mm, 0.298±0.009 and 195±12, respectively. There were significant differences in the specific surface area and mean gray value among all the groups (F = 9.322, 76.560, P < 0.05). Conclusion The pancreatic injury after autologous liver transplantation is related to the energy metabolism of the pancreatic cells induced by hypoxia.
3.Mechanism research of alleviating rat liver ischemia-reperfusion injury by Astilbin
Yubin XU ; Xu'nan MAO ; Guangcai XU ; Lide TAO ; Jie ZHANG ; Chaochen WANG ; Peijian ZHANG ;
International Journal of Surgery 2016;43(7):450-454,封3
Objective To explore the protective effect of astilbin in hepatic ischemia-reperfusion injury (HIRI).Methods SD rats were divided into Sham group (control group),HIRI group (ischemia-reperfusion group),astilbe (low dose group,middle dose group,high dose group),and estabilished the model of rat HIRI.After liver were reperfused with blood (in 4 h,8 h,16 h),collecting the specimens of blood and liver tissues.Detection of serum alanine aminotransferase (ALT),aspertate aminotransferase (AST);Then observed the changes of liver cell microstructure;Western blot analysised the expression of HMGB1,TLR4,NF-kB,TNF-α in liver tissue.Results The serum ALT levels of Sham group in 4 h,8 h,16 h were (58.11 ±4.81) U/L,(57.12 ± 5.33) U/L,(57.63 ±4.54) U/L,the serum ALT levels of HIRI group in 4 h,8 h,16 h were (540.38 ± 21.41) U/L,(831.21 ± 20.11) U/L,(191.95 ± 15.35) U/L.Compared with Sham group,the serum ALT levels of HIRI group were significantly increased(P < 0.01).Compared with HIRI group,The serum ALT levels of three dose groups in 4 h,8 h,16 h were significantly declined,including high dose group lower the most obvious (The serum ALT levels of high dose group in 4 h,8 h,16 h were (223.75 ± 10.53) U/L,(412.14 ±23.59) U/L,(205.25 ± 15.48) U/L (P <0.01).The results of light microscope indicated that drug groups significantly reduce the liver cell damage.The results of Western blot displayed that High dose group of HMGB1,TLR4 protein expression in 4 h,8 h,16 h drop significantly than HIRI group(P <0.05).High dose group of NFkB,TNF-α protein expression in postoperative 8 h,16 h decrease significantly than HIRI group (P < 0.05),but in postoperative 8 h,there was no statistically significant difference compared with group HIRI (P>0.05).Conclusion Astilbe pretreatment can reduce HIRI and its mechanism may be associated with downregulating the axis of HMGB1/TLR4/NF-kB/TNF-α,proceed to the next inhibiting the inflammatory response.
4.Research status and prospect of pancreatic fistula after laparoscopic pancreaticoduodenectomy
International Journal of Surgery 2024;51(2):123-129
With the rapid development of laparoscopic techniques, the safety of laparoscopic surgery has gradually been recognized. Its advantages, including clear visualization, minimal trauma and faster recovery, are increasingly favored by surgeons and patients. Common postoperative complications of laparoscopic pancreaticoduodenectomy include pancreatic fistula, bleeding, gastric paresis, pancreatic insufficiency, and wound infection. Among them, postoperative pancreatic fistula and its related complications are the leading causes of mortality after laparoscopic pancreaticoduodenectomy. This article present an overview of the understanding of postoperative pancreatic fistula, combined with recent research progress in this field, to explore the potential mechanisms of pancreatic fistula occurrence and development, and also summarize the predictive models for postoperative pancreatic fistula and discuss the future trends in laparoscopic pancreaticoduodenectomy.
5.Relationship between CD36 and cell proliferation and migration in hepatocellular carcinoma and its effect on human hepatocellular carcinoma cell xenograft models in nude mice
Lihong ZHANG ; Wei WU ; Guangcai XU ; Peijian ZHANG ; Lide TAO
Cancer Research and Clinic 2024;36(2):98-104
Objective:To observe the expression of CD36 in hepatocellular carcinoma tissues and cell lines, and to investigate the effects of CD36 on the proliferation and migration abilities of human hepatocellular carcinoma cell lines and human hepatocellular carcinoma cell xenograft models in nude mice.Methods:Differences in the expression levels of CD36 transcripts in 371 hepatocellular carcinoma and paracancerous tissues were analyzed based on information from The Cancer Genome Atlas (TCGA) database. Cancer tissues and corresponding paracancerous tissues of 48 hepatocellular carcinoma patients who were diagnosed and underwent surgical treatment at the Affiliated Hospital of Yangzhou University from January 2019 to February 2021 were prospectively collected, and the levels of CD36 mRNA in the tissues were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) method. Western blotting was used to detect CD36 protein levels in human hepatocellular carcinoma cell lines Huh7 and HCCLM3 and human normal liver cell line LO2. Plasmids containing CD36 interfering sequences and empty plasmids were transfected into Huh7 cells or HCCLM3 cells for sh-CD36 group and control group, respectively. The CCK-8 assay was used to detect the proliferation ability (expressed as absorbance value) of cells in each group at 0, 12, 24, 36, 48 and 60 h of culture, and the scratch healing assay and Transwell assay were used to detect the migration ability of cells in each group. The Huh7 cells of sh-CD36 group or control group were injected into the axillary subcutis of BALB/c nude mice, with 4 mice in each group, to construct nude mice models of human hepatocellular carcinoma xenografts; the long and short diameters of tumor were measured weekly after 1 week of inoculation, and the tumor volume was calculated. The nude mice were put to death after 5 weeks of inoculation, and the tumor specimens were collected and weighed; the tumor cell morphology was observed under the microscope, and the expressions of CD36 and Ki-67 proteins in the tumor tissues was detected by immunohistochemistry (IHC).Results:Analysis of the data from the TCGA database showed that the level of CD36 transcripts was higher in hepatocellular carcinoma tissues compared with that in paracancerous tissues (4.2±1.8 vs. 3.2±1.5, t = 2.28, P = 0.035). Tissues detection using qRT-PCR in 48 patients with hepatocellular carcinoma showed that the relative expression of CD36 mRNA in hepatocellular carcinoma tissues was higher than that in paracancerous tissues (0.76±0.26 vs. 0.48±0.23, t = 3.52, P < 0.001). Western blotting assay showed that CD36 protein level in Huh7 and HCCLM3 cells was higher than that in LO2 cells, which were (1.42±0.11) times and (1.68±0.16) times higher than LO2 cells, respectively (both P < 0.001). At the mRNA and protein levels, the CD36 of Huh7 and HCCLM3 cells in the sh-CD36 group was lower than that in the corresponding control group (both P < 0.001). CCK-8 assay showed that the proliferative ability of Huh7 cells and HCCLM3 cells in the sh-CD36 group was lower than that in the corresponding control group after 36 and 24 h of culture (both P < 0.01). Scratch healing assay showed that the scratch healing rates of Huh7 cells [(12±3)% vs. (30±5)%, t = 4.01, P < 0.001] and HCCLM3 cells [(15±4)% vs. (29±5)%, t = 4.16, P < 0.001] in the sh-CD36 group were lower than those in the corresponding control group at 48 h of culture; Transwell assay showed that the number of Huh7 cells [(46±6) cells/field of view vs. (88± 6) cells/field of view, t = 5.56, P < 0.001] and HCCLM3 cells [(42±5) cells/field of view vs. (82±7) cells/field of view, t = 5.34, P < 0.001] penetrating into the membrane in 24 h in the sh-CD36 group was less than that in the corresponding control group. Five weeks after subcutaneous injection, the tumor volume [(682±268) mm 3vs. (1 375±512) mm 3, t = 4.73, P = 0.006] and tumor mass [(432±95) mg/mouse vs. (871±109) mg/mouse, t = 6.57, P < 0.001] of nude mice injected with Huh7 cells of the sh-CD36 group were lower than those of nude mice injected with Huh7 cells of the control group; under the microscope, the density of tumor cells in transplanted tumor specimens of nude mice injected with Huh7 cells of the sh-CD36 group was lower than that in nude mice injected with Huh7 cells of the control group, and the expression levels of both CD36 and Ki-67 proteins were also low. Conclusions:CD36 expression is up-regulated in cancer tissues of hepatocellular carcinoma patients and human hepatocellular carcinoma cell lines Huh7 and HCCLM3, and it may associate with cell proliferation and migration of hepatocellular carcinoma. Knockdown of CD36 expression significantly inhibits the proliferation and migration abilities of hepatocellular carcinoma cells in vitro, and inhibits the tumors of human hepatocellular carcinoma cell xenograft models in nude mice.
6.Analysis and prospect of microwave ablation for hepatocellular carcinoma
Zeyu WANG ; Shihua HAO ; Lide TAO
International Journal of Surgery 2022;49(12):853-859
The global incidence of liver cancer has remained elevated for a long time. As a high-risk country for hepatitis B, China has one of the highest rates of liver cancer in the world. Historically, surgical excision has been the recommended method of treatment for early-stage liver cancer. With the advancement of imaging technology and the growing use of physical treatment in clinics in recent years, microwave ablation has emerged as a new treatment option for patients with small hepatocellular carcinoma and those who have missed the chance for surgery. It is less traumatic, requires less time in the hospital, and is less expensive than the traditional surgery. However, due to several current indication limits and the inability to totally avoid postoperative sequelae, microwave ablation is not appropriate for all patients with liver cancer. This article examines the use, combined therapy, and postoperative consequences of microwave ablation in the treatment of hepatocellular carcinoma, as well as the potential future direction of development in the treatment of hepatocellular carcinoma.
7.Application of 3D printing in surgical treatment of hepatobiliary malignancies
Shihua HAO ; Zeyu WANG ; Lide TAO
International Journal of Surgery 2023;50(4):285-288,F4
At present, surgical treatment is the most effective method for the treatment of hepatobiliary malignant tumor. However, due to the complex anatomical structure of hepatobiliary region, accompanied by vascular variation, and with the continuous update of medical concepts, the requirements for surgery are more strict. Traditional imaging examination has reached a bottleneck in the support of surgical treatment, while 3D printing technology is compared with the former. It showed strong advantages in preoperative program planning and improving the effect of intraoperative precise resection. At the same time, it also shows great potential for medical assistance and disease treatment in the production of bioactive models, and 3D printing technology has obviously enhanced the understanding of surgery for young doctors, and medical staff can create a variety of highly practical 3D printing models under the existing conditions. In the future, it is expected to overcome the limitations of materials and technology and bring higher therapeutic benefits for the majority of patients.
8.Therapeutic effect of anterior approach combined with liver hanging maneuver for right hepatectomy in patients with large hepatocellular carcinoma
Jun WU ; Kai YIN ; Jianwei XU ; Lide TAO ; Lihong ZHANG
Chinese Journal of General Surgery 2019;34(9):787-790
Objective To evaluate hepatectomy by anterior approach combined with liver hanging maneuver against conventional right hepatectomy in patients with large hepatocellular carcinoma (HCC).Methods Of the 62 cases,29 patients underwent anterior approach hepatectomy and 33 did conventional hepatectomy.Results The overall operative time (t =1.815,P =0.037) and parenchymal transsection time (t =4.591,P=0.000) were longer in the anterior approach group than in the conventional group.More cases got radical resection in the anterior group (x2 =7.280,P =0.007).Log-rank test showed that 1,3 and 5-year overall survival rate (OS) in the anterior approach group and the conventional group was 86.1%,50.1%,32.6% vs 75.8%,30.3%,18.9%,respectively (x2 =5.24,P=0.022),1,3 and 5-year disease free survival rate (DFS) were 75.3%,42.1%,31.0% vs 66.1%,24.4%,10.1%,respectively (x2 =4.38,P =0.037),and recurrence rate were 23.6%,49.5%,64.8% vs 36.7%,63.7%,82.5%,respectively (x2 =5.61,P =0.018).Conclusion Long term survival of patients with large sized HCC undergoing hepatectomy through the anterior approach combined with liver hanging maneuver is better than that of conventional approach.
9.Clinical application of 3D printing technique in treatment of intracranial aneurysms
Xiying QIAN ; Lide JIN ; Weihua TAO ; Jianhua ZHAO ; Sunquan HONG
Chinese Journal of Neuromedicine 2016;15(5):483-485
Objective To investigate the clinical application value of 3D printing technique in the treatment ofintracranial aneurysms.Methods Eight patients with intracranial aneurysms,admitted to our hospital from May 2014 to June 2015,were chosen in our study;three dimensional reconstructions of anatomical models were accomplished by computer aided technology.By rapid prototyping,the intracranial aneurysm models were manufactured,operation project were formulated and preoperative sham-operation was enforced to supervise the intracranial aneurysm clipping.The clinical data and clipping efficacy were retrospectively analyzed.Results Eight patients with 11 intracranial aneurysms at stage Ⅰ were treated successfully with aneurysm clipping via unilateral craniotomy without rupture of aneurysms.Preoperative sham operation shortened the time of operation and reduced the postoperative complications.Glasgow outcome scale scores at hospital discharge indicated that good recovery was noted in 7 patients and mild disability in one.Postoperative CTA or DSA did not show residual aneurysms.Conclusions Three-dimensional printing technology can overall,intuitively,exactly display three-dimensional shape of intracranial aneurysms and spatial relation of anatomic structure.It has important role of supervising treatment of intracranial aneurysms and broad application perspective,thus deserves generalization.
10.Design and application of a retractable scalpel handle
Guodong ZHANG ; Qingbo FENG ; Yuan GAO ; Xinyu YU ; Hexing MA ; Lide TAO
Chinese Critical Care Medicine 2020;32(7):869-870
The scalpel is the most practical tool for surgeons. The traditional scalpel is a blade with a split handle, but the length of the blade cannot be adjusted, and it is easy to scratch medical staff. In order to solve the above problems, a retractable scalpel handle was designed by the medical staffs of department of general surgery, Affiliated Hospital of Yangzhou University (Clinical Teaching Hospital of Dalian Medical University), and obtained the National Utility Model Patent of China (ZL 2019 2 0203154.9). The telescopic scalpel adopted the design of rotary telescopic sleeve and threaded column handle to achieve the purpose of built-in blade. By rotating the handle at one end of the handle, the length of the surgical blade extending out of the sleeve could be adjusted according to the actual needs. The structure of the device is simple and easy to operate. The adjustable blade length could also achieve the purpose of accurate operation while effectively avoiding the injury of medical personnel during the operation.