1.Current status of surgery for portal hypertension in China: a national multi-center survey analysis
Lei ZHENG ; Haiyang LI ; Jizhou WANG ; Xiao LIANG ; Jian DOU ; Jitao WANG ; Qiang FAN ; Xiong DING ; Wenlong ZHAI ; Yun JIN ; Bo LI ; Songqing HE ; Tao LI ; Jun LIU ; Kui WANG ; Zhiwei LI ; Yongyi ZENG ; Yingmei SHAO ; Yang BU ; Dong SHANG ; Yong MA ; Cheng LOU ; Xinmin YIN ; Jiefeng HE ; Haihong ZHU ; Jincai WU ; Zhidan XU ; Dunzhu BASANG ; Jianguo LU ; Liting ZHANG ; Jianguo ZHAO ; Ling LYU ; Guoyue LYU ; Nim CHOI ; To Tan CHEUNG ; Meng LUO ; Wanguang ZHANG ; Xiaolong QI ; Xiaoping CHEN
Chinese Journal of Organ Transplantation 2023;44(3):152-159
Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.
2.Clinical application of two kinds of minimally invasive methods in choledocholithiasis complicated with gallbladder stones
Shizhou LIU ; Jiefeng HE ; Yanjun LI
Chinese Journal of Pancreatology 2022;22(1):61-65
Objective:To compare the clinical effectiveness of laparoscopic cholecystectomy (LC)+ laparoscopic choledocholithotomy (LCBDE)+ one-stage suture and primary choledocholithotomy with endoscopic retrograde cholangiopancreatography (ERCP)+ endoscopic duodenal sphincterotomy (EST)+ nasobiliary drainage (ENBD)+ LC in the treatment of choledocholithiasis complicated with gallbladder stones.Methods:A total of 200 patients with choledocholithiasis complicated with gallbladder stones admitted to the General Surgery Department of Shanxi Bethune Hospital from June 2015 to February 2021 were collected, and patients were divided into LC+ LCBDE+ one-stage suture (one-stage suture group, n=130) and ERCP+ EST+ ENBD+ LC (endoscopic surgery group, n=70) according to different treatments. The amount of intraoperative blood loss, operation time, postoperative feeding time, postoperative incidence of pancreatitis, cholangitis and other complications (biliary leakage, abdominal bleeding, wound infection), hospitalization costs, postoperative hospital stay, etc were compared between two groups. Results:The postoperative incidence of pancreatitis in the one-stage suture group (0.7% vs 5.7%) and the hospitalization cost [(2.74±0.39) ten thousand yuan vs (3.86±0.63) ten thousand yuan] were significantly lower than those in the endoscopic surgery group. The operation time [(103.21±9.36) min vs (88.18±7.20)min] was significantly longer than that of the endoscopic surgery group, and postoperative feeding time [(3.3±0.3)d vs (2.2±0.8)d] were significantly later than the endoscopic surgery group ( P<0.05). The amount of intraoperative blood loss [(36.0±3.0)ml vs (37.3±2.7)ml], the incidence of postoperative cholangitis (1.5% vs 2.9%) and other complications [biliary leakage (2.3% vs 1.4%), abdominal bleeding (1.5% vs 4.3%), wound infection(0 vs 0)], postoperative hospital stay [(6.8±1.3)d vs (7.1)d] had no significant differences between the two group. Conclusions:The two minimally invasive methods for the treatment of choledocholithiasis complicated with gallbladder stones had good efficacy, but LC+ LCBDE+ one-stage suture can retain the sphincter function of Oddis, maintain the normal anatomy and physiology of the biliary tract, reduce the incidence of related complications, and contribute to the recovery of patients, with high safety, effectiveness and feasibility.
3.Effects of early postoperative enteral nutrition in combination of micro-ecological feed preparations on intestinal flora and immune function in elderly colorectal cancer patients after surgery
Jiefeng LIU ; Miao HE ; Xinyu ZENG ; Yujing GONG
Chinese Journal of Geriatrics 2020;39(4):435-438
Objective:To investigate effects of early postoperative enteral nutrition in combination of micro-ecological feed preparations on intestinal flora and immune function in elderly colorectal cancer patients after surgery.Methods:Eighty-eight elderly colorectal cancer patients treated at our hospital from November 2017 to August 2019 were enrolled in the study.They were randomly divided into two groups(n=44, each): the observation group receiving micro-ecological feed preparations and enteral nutrition, and the control group receiving conventional parenteral nutrition.The intestinal flora index, cellular immune function, humoral immune function and complications were compared between the two groups.Results:There was no significant difference in the indices of intestinal flora between the two groups before operation(all P>0.05). In the control group, Bifidobacteria and Lactobacillus decreased, E. coli increased, and B/E value decreased after surgery compared with before surgery( P<0.05). In the observation group, Bifidobacteria and Lactobacillus decreased, E. coli increased and B/E value decreased after surgery compared with before surgery( P<0.05). Compared with the control group, the observation group showed that Bifidobacteria and Lactobacillus increased, E. coli decreased and B/E value increased after surgery( P<0.05). Serum inflammatory factors had no statistically significance difference between the two groups before operation( P>0.05). Levels of interleukin-6, C-reactive protein and tumor necrosis factor-α were increased in the two groups after surgery compared with before surgery( P<0.05), and the indexes were lower in the observation group than in the control group( t=4.841, 7.247 and 4.231, all P=0.000). Levels of IgG, IgM, IgA, CD3 + , CD4 + , CD8 + and the ratio of CD4 + and CD8 + were higher in the observation group than in the control group[(12.53±1.84) g/L vs.(11.47±1.92)g/L, (1.45±0.22) g/L vs.(1.33±0.17) g/L, (2.28±0.24) g/L vs.(2.13±0.12) g/L, (52.84±4.12)% vs.(50.43±3.91)% , (34.53±3.51)% vs.(30.75±3.62)%, (19.09±2.41)% vs.(18.24±0.53)% and (1.68±0.22)% vs.(1.43±0.15)%, t=2.644, 2.863, 3.120, 2.814, 4.973, 2.285 and 6.228, P=0.010, 0.005, 0.003, 0.006, 0.000, 0.025 and 0.000]. Conclusions:Early micro-ecological feed preparation in combination of enteral nutrition can improve the surgical effect and quality of life and promote disease recovery with a safety in patients with colorectal cancer.
4.Application of the pathological classification of "CCCG-WT-2016" (2019 revision) for treatment of Wilms tumors
Qiao HE ; TouEn Kenneth CHANG ; Wanwan CHEN ; Jing MA ; Ping SHEN ; Jiefeng CHEN ; Xiaoting JIN ; Zhongde ZHANG ; Minzhi YIN
Chinese Journal of Pathology 2020;49(4):324-328
Objective:To describe our experiences in application of the 2019 revision of "CCCG-WT-2016" for the diagnosis of Wilms tumors.Methods:Ninety-one cases of Wilms tumor diagnosed at Shanghai Children′s Medical Center from January 2015 to December 2018 were collected. All cases were reviewed by two senior pathologists, including one from China and the other from Singapore, according to the 2019 revision of "CCCG-WT-2016."Results:The specimens were obtained by core biopsy ( n=21), primary nephrectomy ( n=41), post-chemotherapy nephrectomy/resection ( n=18), or biopsy/resection of metastatic/relapse/post-chemotherapy metastatic lesion(s) ( n=11). The specimens of core biopsy and primary nephrectomy ( n=62) all had favorable histology.Twelve post-chemotherapy nephrectomy cases were subdivided into three risk groups: low risk ( n=0), intermediate risk ( n=10) and high risk ( n=2). Six post-chemotherapy resection cases were subdivided into 3 risk groups:low risk ( n=0), intermediate risk ( n=5) and high risk ( n=1). The remaining 11 cases were comprised of metastatic, relapse, and post-chemotherapy metastatic lesions. The concordance rate of the two senior pathologists was 100%(91/91). Conclusions:The 2019 revision of "CCCG-WT-2016" is clearly written and easy to use. It can serve as the basis of accurate classification for clinical treatment.
5.Clinicopathological characteristics of NTRK-rearranged mesenchymal tumors in childhood
Minzhi YIN ; Jing MA ; Qiao HE ; Ping SHEN ; Jiefeng CHEN ; Xiaoting JIN ; Zhongde ZHANG ; Hong Chik KUICK ; Huiyi CHEN ; Ng Eileen Hui Qi ; Jet Sze AW ; Chang Kenneth Tou En
Chinese Journal of Pathology 2020;49(7):675-680
Objective:To investigate the clinical and pathological features of pediatric NTRK-rearranged tumors.Methods:Four NTRK-rearranged soft tissue tumors and one renal tumor at Shanghai Children′s Medical Center, Shanghai Jiaotong University and Singapore KK Women′s and Children′s Hospital from January 2017 to September 2019 were identified. Pan-TRK immunohistochemistry, and the ALK and ETV6 gene break-apart fluorescence in situ hybridizations (FISH) were performed. NTRK gene rearrangement was detected using sequencing-based methods.Results:There were 3 males and 2 females in this study. The patients were between 3 months and 13 years of age. Histologically, the tumors were infiltrative spindle cell tumors with variable accompanying inflammatory cells. Immunohistochemistry showed positive reactivity for pan-TRK in all tumors, with nuclear staining for NTRK3 fusion, and cytoplasmic staining for NTRK1 fusion. The molecular testing revealed NTRK gene fusions (one each of TPM3-NTRK1, ETV6-NTRK3 and DCTN1-NTRK1, and two cases of LMNA-NTRK1). Two patients were receiving larotrectinib. The others were are well without disease, with follow-up durations of 9 to 29 months.Conclusions:NTRK-rearranged mesenchymal tumors from soft tissue sites and kidney are identified. A novel DCTN1-NTRK1 fusion is described. Pan-TRK immunohistochemistry is useful for diagnosis. NTRK-targeted therapy may be an option for unresectable, recurrent or metastatic cases.
6.Application value of early and delayed laparoscopic cholecystectomy after percutaneous transhepatic gall-bladder drainage in 65 years of age or older patients with severe acute cholecystitis: a prospective analysis
Zhengzheng YAN ; Jiefeng HE ; Jun XING
Chinese Journal of Digestive Surgery 2019;18(5):447-452
Objective To investigate the application value of early and delayed laparoscopic cholecystectomy (LC) after percutaneous transhepatic gallbladder drainage (PTGD) in 65 years of age or older patients with severe acute cholecystitis.Methods The prospective study was conducted.The clinical data of 80 patients with severe acute cholecystitis who were admitted to Shanxi Dayi Hospital of Shanxi Academy of Medical Sciences from May 2016 to January 2018 were collected.All patients were divided into two groups by random number table,including patients undergoing LC 72 h later after extubation of PTGD in the PTGD + early LC group,and patients undergoing LC 5-14 days later after extubation of PTGD in the PTGD + delayed LC group.Observation indicators:(1) surgical situations;(2) analysis of liver function before and after LC in the two groups;(3) analysis of serum-related inflammatory factors before and after LC in the two groups;(4) follow-up situations.Patients were followed up by outpatient examination or telephone interview to detect the postoperative complications in the postoperative three months up to April 2018.Measurement data with normal distribution were represented as Mean ± SD,and comparison between groups was done using the paired t test.Count data were represented as absolute number,and comparison between groups was analyzed using the chi-square test or Fisher exact probability.Results Eighty patients were screened for eligibility,including 41 males and 39 females,aged from 65 to 70 years,with an average age of 67 years.There were 40 patients in the PTGD + early LC group and 40 in the PTGD + delayed LC group,respectively.(1) Surgical situations:the operation time,volume of intraoperative blood loss,and duration of postoperative hospital stay were (52± 15) minutes,(29± 11) mL,(18.9± 1.6) days in the PTGD + early LC group,and (88± 13)minutes,(69± 11)mL,(27.7±4.8)days in the PTGD + delayed LC group,respectively,showing significant differences in the above indicators between the two groups (t =11.668,16.219,11.000,P<0.05).(2) Analysis of liver function before and after LC in the two groups:the levels of aspartate transaminase (AST),alanine aminotransferase (ALT),gamma glutamyl transferase (GGT),and total bilirubin (TBil) of PTGD + early LC group were (53 ± 11) U/L,(203 ±40) U/L,(128± 22) U/L,(19± 6)U/L,(86±21)μmol/L before LC,and (26±5)U/L,(83±23)U/L,(29±3)U/L,(11±5)U/L,(27± 7) μmol/L at 24 hours after LC,showing significant differences in the above indicators before and after LC (t =12.562,16.448,28.199,6.478,16.857,P<0.05).The levels of AST,ALT,GGT,and TBil of PTGD + delayed LC group were (54± 12) U/L,(203±48) U/L,(130±24) U/L,(19±6) U/L,(85±20) μmol/L before LC,and (29±5) U/L,(151±36) U/L,(53±7)U/L,(17±3)U/L,(31±8)μmol/L at 24 hours after LC,showing significant differences in the above indicators before and after LC (t =13.622,5.481,2.169,1.988,15.855,P<0.05).There was no significant difference in the levels of AST,ALT,ALP,GGT,TBil before LC between the two groups (t=0.389,0.000,0.389,0.000,0.218,P>0.05),meanwhile,there were significant differences in the levels of AST,ALT,ALP,GGT,TBil after LC between the two groups (t =2.683,10.067,19.931,6.508,2.380,P<0.05).(3) Analysis of serum-related inflammatory factors before and after LC in the two groups:the levels of interleukin-1 (IL-1),interleukin-6 (IL-6),high-sensitivity C-reactive protein (CRP),interleukin-10 (IL-10),and tumor necrosis factor-α (TNF-α) of PTGD + early LC group were (71 ±9) ng/L,(82±9)ng/L,(137±16)ng/L,(75±6)ng/L,(67±9)μg,/L before LC,and (87±13)ng/L,(97±9)ng/L,(81± 19)ng/L,(145±6)ng/L,(85±6)μg/L at 24 hours after LC,showing significant differences in the above indicators before and after LC (t ==6.400,7.454,14.259,52.175,10.525,P<0.05).The levels of IL-1,IL-6,high-sensitivity CRP,IL-10,and TNF-α of PTGD + delayed LC group were (71±9) ng/L,(82± 10) ng/L,(145±28)ng/L,(75±6)ng/L,(67±10) μg/L before LC,and (145±7)ng/L,(135±16) ng/L,(101±1S)ng/L,(146±9) ng/L,(113±10)μg/L at 24 hours after LC,showing significant differences in the above indicators before and after LC (t =41.079,17.766,8.360,41.525,27.578,P < 0.05).There was no significant difference in the levels of IL-1,IL-6,high-sensitivity CRP,IL-10,and TNF-α before LC between the two groups (t =0.000,0.000,1.569,0.000,0.000,P>0.05),meanwhile,there were significant differences in the levels of IL-1,IL-6,high-sensitivity CRP,and TNF-α after LC between the two groups (t=24.844,13.092,4.833,15.185,P<0.05).(4) Follow-up situations:80 patients were followed up for 3 months.Two patients in the PTGD + early LC group had postoperative complications,including 1 of bile duct injury and 1 of incisional infection;9 patients of PTGD + delayed LC group had postoperative complications,including 3 of bile duct injury,3 of multiple organ failure,2 of incisional infection,1 of death.There was a significant difference in the postoperative complication between the two groups (x2 =5.165,P<0.05).Conclusion Early LC after PTGD can effectively shorten operation time,reduce volume of intraoperative blood loss,shorten duration of postoperative hospital stay,protect liver function,reduce the expression of serum inflammatory factors at 24 hours after surgery,and reduce postoperative complications.
7.Effect of CNOT7 Gene Knockdown on the Immune Microenvironment of HepG2 Cells by Reduced TGF-β1 Secretion
Shun GUO ; Haichao ZHAO ; Xiaojing REN ; Chongren REN ; Jiefeng HE ; Haoliang ZHAO
Journal of China Medical University 2019;48(3):225-229
Objective To study the effect of human CCR4-NOT transcription complex subunit 7 (CNOT7) gene knockdown on the immune microenvironment of HepG2 cells and explore its significance. Methods We designed a cell transfection protocol and performed the experiment with three groups:CNOT7-targeted knockdown group, control group, and CNOT7 overexpression group. The transfection efficiency was assessed using inverted fluorescence microscopy, and the expression level of CNOT7, transforming growth factor-β1 (TGF-β1), and nuclear factor-kappa B (NF-κB) p65 proteins was determined by Western blotting. The concentration of TGF-β1 secreted in the cell culture supernatant was measured by ELISA. The sensitivity of tumor cells to the killing function of natural killer (NK) cells was detected by flow cytometry. Results Compared with the control group, the expression level of TGF-β1 and NF-κB p65 proteins was significantly decreased in the CNOT7-targeted knockdown group, and the TGF-β1 concentration in the culture supernatant was also significantly reduced. However, in the CNOT7 overexpression group, the expression level of the two proteins and TGF-β1 concentration were significantly increased. NK cells were co-cultured with tumor cells, and the apoptosis rate of HepG2 cells transfected with CNOT7-specific shRNA was significantly increased. However, in the CNOT7 overexpression group, the apoptosis rate was significantly decreased. Conclusion CNOT7 forms the immune microenvironment of hepatocellular carcinoma. Targeted knockdown of CNOT7 can reduce TGF-β1 secretion and enhance the killing function of NK cells toward HepG2 cells.
8.The immune microenvironment in hepatocellular carcinoma and the potential mechanism
Haichao ZHAO ; Shun GUO ; Chongren REN ; Xiaojing REN ; Xidong CHEN ; Changzhou CHEN ; Jian LI ; Jiefeng HE ; Haoliang ZHAO
Chinese Journal of Hepatobiliary Surgery 2019;25(4):259-263
Objective To analyze tumor immune microenvironment and related mechanisms in liver cancer.Methods We included 10 cases of hepatocellular carcinoma,hepatitis B patients and healthy volunteers from January 2015 to December 2017 in Shanxi Grand Hospital.We first detected the peripheral and local GM-CSF level in each group,detected myeloid-derived suppressor cells (MDSCs) GM-CSF and pathway-related protein expression.from liver cancer,tumor margin and normal liver tissue through flow cytometry and immunohistochemistry,Finally,we transfected the CCR4-NOT transcriptional complex subunit 7 (CNOT7) recombinant plasmid in the hepatoma cell line,and then detected the related protein expression.Results There was no significant difference for peripheral blood GM-CSF level between liver cancer group,hepatitis group and control group (P>0.05).The level of local GM-CSF was (32.2±8.9) ng/L,which was higher than that of hepatocellular carcinoma (9.7±2.7) ng/L and normal liver tissue (11.6±2.9) ng/L.The difference was statistically significant (P<0.05).The proportion of MDSCs at the edge of the tumor was (9.9 ±3.6) %,which was higher than that of liver cancer (4.0± 1.5) % and normal liver tissue (6.3±2.3) %,and the difference was statistically significant (P<0.05).Immunohistochemistrydata was consistent with previous data.Compared with normal liver tissue,CNOT7 and STAT3 were highly expressed in liver cancer tissues,while STAT1 was lowly expressed.HepG2 human hepatoma cells were selected for transfection.Compared with the empty plasmid group,CNOT7 expression was decreased in the knocking out group at the same time STAT1 expression was increased,STAT3 and GM-CSF expression was decreased.Conclusion In hepatocellular carcinoma,the secretion of GM-CSF increased and the number of MDSCs increased.Knocking out CNOT7 reduced GM-CSF secretion and activate the JAK/STAT signaling pathway.
9.Expression of miR-103a-3p in breast cancer tissues and its suppression on glycolysis and proliferation of breast cancer cells via down-regulating PDK4
ZHANG Yazhen ; HE Guisheng ; WU Xiaoming ; SONG Jiefeng ; WU Huangfu
Chinese Journal of Cancer Biotherapy 2018;25(5):490-496
[Abstract] Objective: : To explore miR-103a-3p expression in the tumor tissues and the serum of breast cancer patients, and its role and mechanism in breast cancer development. Methods: Pathologically confirmed 31 cases of tumor tissues and 21 cases of para-cancerous tissues resected at Department of Oncological Surgery of the Second Affiliated Hospital of Hainan Medical University (Haikou, China) from March 1, 2017 to August 31,2017 were collected for this study; in addition, serum samples from 38 breast cancer patients and 22 healthy subjects as well as the breast cancer cell lines MCF-7 and MDA-MB-231 were used in this study. pHBLV-U6-Luc-T2A-Puro and PLL3.7 lentivirus were applied to knock down miR-103a-3p and PDK4 in MCF-7 and MDA-MB-231 cells, respectively. qPCR and Western blotting were performed to examine the mRNA and protein expressions of miR-103a-3p and PDK4 in tissues and serums of breast cancer patients as well as the in cell lines, respectively; CCK-8 assay was applied to detect the proliferation of MCF-7 and MDAMB-231 cells; Olympus AU5400 was applied to detect the glucose consumption and lactate production in indicated cell line. Results: : miR-103a-3p was significantly decreased in tumor tissues compared with the paracancerous tissues (P<0.01). miR-103a-3p knockdown activated the glucos consumption and lactate production (all P<0.01), increased the PKD4 expression (P<0.01) in MCF-7 and MDAMD-231 cells, and promoted the proliferation of MCF-7 and MDA-MB-231 cells (P<0.01). Furthermore, knockdown of PDK4 suppressed the glucose consumption, lactate production and proliferation in MCF-7 and MDA-MB-231 cells with miR-103a-3p silencing (all P<0.01). Conclusion: :In the breast cancer, miR-103a-3p inhibited the proliferation of breast cancer cells through down-regulation of PDK4 and PDK4-mediated aerobic glycolysis.
10.The effect of glycated polylysine-coupled MIP-3α-FL on the immune microenvironment of mouse liver cancer
Haichao ZHAO ; Shun GUO ; Chongren REN ; Jiefeng HE ; Haoliang ZHAO
Chinese Journal of General Surgery 2018;33(7):596-600
Objective To study the regulation of dendritic cells by recombinant glycated polylysine-coupled MIP-3α-FL double-gene targeting expression vector in liver cancer immune microenvironment.Methods H22 hepatocarcinoma cells were transfected with recombinant plasmid of MIP-3α-FL (shMIP-3α-FL) and injected into hepatoma model mice.The survival time,tumor size were compared.Flow cytometry was used to measure the number and phenotype of tumor infiltrating DCs.Results Western blot and ELISA demonstrated that the secretion of MIP-3α and FL in H22 cells was significantly increased after transfection with MIP-3α-FL.The survival time of the mice in the experimental group was significantly prolonged,the tumor size decreased.Flow cytometry showed that the number of tumor-infiltrating DCs in the experimental group was significantly higher than that in the control group;the expression of CD80 and CD86 in the infiltrating dendritic cells (TIDCs) was significantly higher than that of the control group.Conclusions The co-action of MIP-3α and FL can significantly promote DC accumulation,maturation,and conjugate glycosylated polylysine carriers increase the precision of targeting and enhance the antigenpresentation of the DCs.

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