1.Ⅰ-stage resection of colon cancer and synchronous liver metastasis after conversion therapy
Chinese Journal of Digestive Surgery 2016;15(2):185-190
Objective To investigate the safety and clinical effect of Ⅰ-stage resection of colon cancer and synchronous liver metastasis after conversion therapy.Methods The retrospective descriptive study was adopted.The clinical data of 1 patient with sigmoid cancer with synchronous multiple liver metastases who was admitted to the Zhongshan Hospital of Fudan University in April 2013 were collected.The patient was diagnosed as sigmoid cancer with multiple lymph nodes surrounding colon and 5 metastatic lesions found in liver by preoperative imaging examination,and the maximum diameters of 2 metastatic lesions were 4.5 cm and 3.6 cm.The pathological results of colonoscopy indicated adenocarcinoma.After discussion of the multidisciplinary team,liver metastatic lesions were significantly reduced through mFOLFOX6 chemotherapy combined with bevacizumab treatment,and then patient underwent Ⅰ-stage resection of colon cancer with synchronous liver metastasis by the surgical procedures of partial hepatectomy + 3D laparoscopy-assisted radical resection of sigmoid cancer.The patient received convention treatment of antibiotic,nutrition support therapy and mFOLFOX6 adjuvant chemotherapy.The changes of lesions in liver and tumor markers were observed by tumor marker test,abdominal/pelvic CT and MRI in the upper abdomen after conversion therapy.The operation time,volume of intraoptrative blood loss,number of lymph nodes dissected and vital sign were observed in the operation.The liver function,time for out-off-bed activity,time to anal exsufflation,time of drainage tube removal,duration of hospital stay,complications,results of pathological examination and recurrence and mnetastasis of tumor were observed after operation.After discharge from hospital,the patient underwent monthly tumor marker test,B ultrasound and chest X-ray examination till January 2014 and abdominaL/pelvic CT,magnetic resonance imaging (MRI) in the upper abdomen and colonoscopy every 6 months.The follow-up of outpatient examination and telephone interview was performed to detect the recurrence and metastasis of tumor up to September 2015.Results After preoperative 4-cycle chemotherapy,the diameters of 2 metastatic lesions in liver reduced to 3.2 cm and 2.0 cm,the levels of carcinoembryonic antigen(CEA) and CA19-9 (tumor marker) were reduced to 95.9 μg/L and 252.4 kU/L.The patient underwent successful Ⅰ-stage resection of colon cancer and synohronous liver metastasis.The operation time,volume of intraoperative blood loss,numbers of lymph nodes dissected and cancerous nodes were 208 minutes,250mL,14 and 1,respectively.The patient had no blood transfusion and metastasis,with the stable vital signs and good postoperative recovery.The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were 1 147 U/L and 2 631 U/L at postoperative day 1,101 U/L and 37 U/L at postoperative day 7,respectively.The out-off-bed activity,anal exsufflation,drainage tube removal and discharge from hospital were occurred at postoperative day 2,3,7 and 9,respectively.No anastomotic fistula,bleeding and infection were occurred aftcr operation.The patient was diagnosed as with ulcerated sigmoid adenocarcinoma in T3N1cM1 stage (combining with liver metastasis).The patient received adjuvant therapy of mFOLFOX6 and oral capecitabine at postoperative day 40,and was followed up for 30 months with a good quality of life and without metastasis and recurrence.Conclusion Ⅰ-stage resection of colon cancer with synohronous liver metastasis can be used for initial unresectable colon cancer with liver metastasis after conversion therapy,and it is safe and feasible,with a good therapeutic effect.
2.Mouse liver phosphoproteome methodology optimization and kinase analysis
Cong LIN ; Liangliang REN ; Ying JIANG ; Fuchu HE
Military Medical Sciences 2015;(6):407-412
Objective To analyze the construction of mouse liver phosphoproteome and phosphorylated kinases to provide useful information for integrating mouse kinase phosphorylation regulatory networks.Methods A new method was established to identify phosphoproteome from the mouse liver.First of all, liver protein was digested with trypsin before the resulting peptides were subjected to a two-step phosphopeptide enrichment and separation procedure consisting of TiO2 chro-maphy enrichment combined with high pHHPLC separation.Samples were injected onto aNanolC-Ultra-2Dplus system cou-pled to an AB-Sciex 5600 Triple TOF mass spectrometer instrument.Then data analysis was performed to provide information of new identified phosphorylation sites of kinase.Results and Conclusion Using our efficient and high-throughput platform, we reported the identification of 5386 phosophorylation sites and 4553 phosphopeptides from 1533 proteins of the mouse liver.126 new phosphorylation sites were identified from 116 kinases, which provides valuable infor-mation for phosphorylation networks in the mouse liver.
3.Construction and application of cell fines screening Mycobacterium tuberculosis-specific tetramers of CD4+α/β T cell receptor
Yi CHEN ; Liangliang REN ; Tao DONG ; Yimin FANG ; Xuanjing DU ; Yan HUANG ; Ming GAO ; Na ZHANG ; Jianbo ZHANG ; Xiaomin LAI
Chinese Journal of Microbiology and Immunology 2009;29(3):271-275
Objective To construct and apply a cell line screening Mycobacterium tuberculosis (Mtb)-specific tetramers of CD4+α/β T cell receptor(TCR). Methods The β chains of HLA class Ⅱ (DR) were amplified from tuberculosis patients by PCR. The pMT-HLA-DRB expression vectors that carries the HLA-DR 13 chain and pMT-HLA-DRA-P expression vectors which carries the genes of HLA-DR α chain loaded with Mtb antigen were transfected into S2 cells with the method of calcium phosphate transfection. The expressed Mtb peptide/HLA-DR complexes were primarily identified by the method of cell immunohistochemistry. The cell lines expressing Mtb peptide/HLA-DR complexes were used to screen tetramers of CD4+ TCR by flow cytometry. Results S2 cell lines expressing Mtb peptide/HLA-DR complexes on the cell surface were obtained, two kinds of Mtb specific tetramers of CD4+α/β TCR were screened. Conclusion S2 cell lines expressing Mtb peptide/HLA-DR complexes on the cell surface provide the solid basis of the further research on the TCR tetramers and are helpful for exploring new diagnostic study methods about tuberculosis and developing new vaccines.
4.Efficacy and Safety of Combined Therapy with 89Sr in Skeletal-Related Events of Prostate Cancer:A Meta-analysis
Liangliang LI ; Xiaoqiang REN ; Ziran XU ; Shiyong XIN ; Jianguo ZHANG
Herald of Medicine 2017;36(12):1404-1410
Objective To evaluate the efficacy and safety of combined therapy with 89Sr for treating skeletal-related events of prostate cancer. Methods Databases including PubMed,MEDLINE,EMBASE,the Cochrane library,CNKI,CBM and Wanfang were systematically searched since 89Sr was first reported in 1976 to September 2015 to include the randomized controlled trials (RCTs) of the combined therapy with 89Sr for skeletal-related events of prostate cancer.The statistical analysis was performed using Review Manager Version 5.2. Results A total of 18 RCTs involving 1 280 patients were analyzed.The results of meta-analysis indicated:there were statistically significant differences in the pain relief rate [OR=4.71,95%CI(3.34, 6.62),P<0.000 1],decrement rate of bone metastasis[OR=3.63,95%CI(2.60,5.09),P<0.000 1] and improvement rate of life quality [OR=2.16,95%CI(1.16,4.02),P<0.05].Progression-free survival of patients in experimental group was significantly longer than that in control group [HR=0.84,95%CI(0.73,0.97),P=0.02].No significant difference was found in overall survival [HR=0.82,95%CI(0.65,1.02),P=0.07].There were no significant differences in the incidence of adverse events [OR=1.46,95%CI(0.98,2.17),P>0.05]. Conclusion Combined therapy with 89Sr has better efficacy and comparable safety profile compared with standard therapy.However,the quality and sample size of the included studies are limited,so more high-quality and large-sample RCTs are needed to verify the validity.
5.Simultaneous pancreas and kidney transplantation for 5 patients with diabetesplus end-stage renal disease
Shengsheng REN ; Liangliang XU ; Turun SONG ; Ming ZHANG ; Tao LIN ; Mingqing XU ; Shifeng LI
Chinese Journal of Organ Transplantation 2019;40(5):272-276
Objective To reduce the perioperative complications of simultaneous pancreas and kidney transplantation (SPK ) and boost the clinical efficacy by exploring its perioperative management in diabetics with end-stage renal disease .Methods Retrospective analysis was performed for the clinical data of 5 diabetics with end-stage renal disease undergoing SPK since 2017 .Results The cold ischemic time of all allografts was under 8 hours .No surgical complications occurred in recipients post-transplantation .Two patients were complicated with hyperkalemia and their serum potassium levels normalized after treatment .One case of bleeding in abdominal cavity was cured conservatively . Renal functions of two patients with delayed renal function post-transplantation gradually recovered after hematodialysis . One case of peritransplant fluid collection recovered after debridement and drainage .Another case of acute left heart failure and cardiac arrest at 45 days post-transplantation resumed normal heart rhythm after rescue .However ,his consciousness could not be restored and his families gave up subsequent treatments . Transplanted kidneys and pancreases of these 4 patients normalized .Follow-up was conducted until March 20 , 2019 . They became insulin and dialysis independent and serum creatinine and blood glucose normalized .Diabetic complications were relieved and their quality-of-life also improved significantly .Conclusions SPK is an effective treatment for diabetics with end-stage renal disease .While maintaining normal serum creatinine and blood glucose , it may liberate patients from insulin dosing and dialytic maintenance ,lower diabetic complications and improve quality-of-life .
6.Construction of hepatocellular carcinoma prognosis risk model and prediction of immunotherapy efficacy
Junqing LI ; Liangliang REN ; Weiran LIN ; Yiting FENG ; Chaoying LI ; Ying JIANG
Chinese Journal of Immunology 2024;40(7):1422-1430
Objective:To construct a prognostic risk model for hepatocellular carcinoma(HCC),and elucidate the immune characteristics and immunotherapy response in patients with different prognostic stratification.Methods:RNA-seq data of TCGA-LIHC and ICGC(LIRI-JP),and gene microarray data of GSE14520 and GSE54236 in hepatocellular carcinoma,as well as clinical informa-tion of the corresponding samples were downloaded.First,screening of differentially expressed genes in tumor and non-tumor tissue samples from TCGA-LIHC,GSE14520 and GSE54236.For the common differential genes,univariate cox regression analysis was per-formed using TCGA-LIHC data to obtain HCC prognosis-related genes.Five genes were randomly selected as a panel,and the optimal prognostic marker panel was screened among 10 000 panels using Lasso-cox regression analysis combined with a five-fold cross-valida-tion method.TCGA-LIHC data were used as training set to construct the prognostic risk model,and ICGC data were used as validation set to test the model performance.Tumor immune dysfunction and exclusion(TIDE)algorithm and Immunophenotypic score(IPS)were used to predict immunotherapy efficacy in patients in different prognostic groups.Results:Overall survival was significantly lon-ger in low-risk group of HCC patients compared with high-risk group.Tumor proliferation rate,Treg and Th2 cell chemotaxis,stromal remodeling,and pro-tumor cytokines were significantly increased in high-risk patients,while NK cells,Th1 cells,effector cells and endothelial cells were significantly increased in low-risk patients.Immune checkpoint analysis showed that PDCD1,CTLA4 and CD276 were up-regulated in high-risk patients,while PDCD1LG2 was upregulated in low-risk patients.TIDE score and IPS results predicted that patients in low-risk group had better efficacy to immunotherapy.Conclusion:This study constructed a prognostic risk model containing three genes,DNASE1L3,RDH16 and DLGAP5,which can effectively predict the prognosis of HCC patients and assist in clinical decision making for individualized immunotherapy.
7.Interventional therapy on hemobilia induced by hepatic artery pseudoaneurysm
Zhen LI ; Liangliang BAI ; Xin LI ; Pengchao ZHAN ; Kun JI ; Kewei REN ; Jianzhuang REN ; Xinwei HAN
Journal of Practical Radiology 2018;34(12):1929-1932
Objective To investigate the safety and feasibility of the interventional therapy on hemobilia induced by hepatic artery pseudoaneurysm(PsAn).Methods The clinical data of 28 patients with hemobilia in our department was analyzed retrospectively.All the patients were firstly treated with internal medicine,and then treated by interventional therapy.The angiography clearly displayed the shape,size and location of the PsAn,and superselective embolism was performed during the operation.The symptomatic treatment and the bile duct drainage were performed after operation.Postoperative follow-up time was 1-3 6 months,and the follow-up endpoint was the death of patient.Results 28 patients were diagnosed as hepatic artery PsAn.The interventional embolization therapy on hemobilia was completely effective.A total of 110 spring coils were applicated in the study,there was no complication related to interventional therapy.One patient with hilar cholangiocarcinoma was dead due to infection and liver failure after four weeks of operation.Two patients with choledochal carcinoma died of tumor progression after 11.5 and 14.2 months of interventional therapy,respectively.In addition,2 patients with gastric carcinoma died of tumor progression after 4 and 6.5 months of operation,respectively,and 1 patient with common bile duct stones who underwent laparoscopic surgery died of complications of coronary heart disease after 5 months of interventional therapy. The other patients all had satisfactory therapeutic effect and recovered well.Conclusion The interventional therapy has definite therapeutic effect on hemobilia induced by hepatic artery PsAn.The technique is worthy of popularized clinically due to its features of simplicity,safety and reliablity.
8.Pharmacokinetics of drug?eluting beads loading arsenic trioxide in the treatment of rabbit VX2 liver tumour
Hao LI ; Xuhua DUAN ; Xinwei HAN ; Jianzhuang REN ; Pengfei CHEN ; Fengyao LI ; Liangliang BAI ; Manzhou WANG
Chinese Journal of Radiology 2019;53(7):615-620
Objective To study pharmacokinetics and tissue distribution of CalliSpheres Beads (CB) loaded Arsenic trioxide (ATO) on rabbit VX2 liver tumor by transcatheter arterial chemoembolization (TACE). Method Sixty four rabbits with VX2 liver tumors were randomly divided into 4 groups: control group, CB group, CBATO group and cTACE group. Blood samples were taken at specific time points after TACE.The blood concentration of ATO,liver and kidney functions were examined respectively. In each group, every 4 rabbits were sacrificed on 1 days,3 days,7 days and 14 days after operation. The tumor,liver,kidney, lung,heart and muscle were taken to detect the drug concentration. Bilateral t?test was used to compare the drug concentration in blood and tissue between CBATO group and cTACE group. Results Statistically,The levels of ALT and AST in group CBATO and cTACE on 1st,3rd and 7th days after TACE were significantly higher than those in CB group(ALT: F=25.872, 17.69, 7.016, AST: F=46.365, 32.385, 12.548, P<0.05) respectively. The ALT and AST levels in CBATO group were statistically lower than those in cTACE group (ALT: t=0.369, 0.432, 0.169, 0.353, AST: t=0.488, 0.593, P>0.05). There were no statistically significant differences in the levels of BUN and Scr between the four experimental groups at each observation time point. Statistically, 10 minutes and 20 minutes after TACE, the blood drug concentration inCBATO was significantly lower than that in cTACE (t=7.675, 6.461, P<0.001). while 12 hours after operation,blood drug concentration in CBATO group was higher than that in cTACE group. In tumor tissue,the concentration of ATO in CBATO was higher than that in cTACE,and there was no statistical differences on the 1st day after TACE(t=2.155, P=0.068), but there was a statistical differences between 3rd, 7th and 14th days (t=11.462, 7.624, 2.649, P<0.05). Conclusion CBATO could prolong the time of drug metabolism,increase the drug concentration in tumor tissue,and didn′t aggravate the damage of liver and kidney function.
9.Clinical value of deubiquitination modification in evaluating the prognosis of patients with diffuse large B-cell lymphoma
Haiqin XU ; Zhihong REN ; Weili XIAO ; Yan YAN ; Liangliang SUN ; Haitao DING
Chinese Journal of Postgraduates of Medicine 2021;44(11):994-998
Objective:To observe the expression levels of small ubiquitinated protein specific protease (SENP) 1 and small ubiquitin-related modifier protein (SUMO) 1 in patients with diffuse large B-cell lymphoma (DLBCL), and analyze the clinical value of evaluating prognosis.Methods:The clinical data of 66 patients with DLBCL (DLBCL group) in Inner Mongolia People′s Hospital from February 2017 to October 2020 were retrospectively analyzed, and 60 cases of healthy people in the same period were selected as the healthy control group. The expression levels of SENP1 and SUMO1 were detected by enzyme linked immunosorbent assay (ELISA). The correlation between the expression levels of SENP1, SUMO1 and clinical characteristics was analyzed. The independent risk factors affecting the prognosis were analyzed by Cox multivariate analysis.Results:The SENP1 in DLBCL group was significantly higher than that in healthy control group (50.39 ± 6.86 vs. 7.47 ± 1.32), the SUMO1 in DLBCL group was significantly lower than that in healthy control group (8.84 ± 2.13 vs. 31.49 ± 5.89), and there were statistical differences ( t = 47.640 and 29.210, P<0.01). There were statistical differences in SENP1 and SUMO1 among patients with different clinical stages ( P<0.01). The expression levels of SENP1 and SUMO1 were correlated with clinical stage and international prognostic index (IPI) ( P<0.05), and were not correlated with age, gender, disease site and clinical symptoms ( P>0.05). The 3-year survival rate in patients with high SENP1 expression (30 cases) was significantly lower than that in patients with low SENP1 expression (36 cases), the 3-year survival rate in patients with high SUMO1 expression (38 cases) was significantly higher than that in patients with low SUMO1 expression (28 cases), and there were statistical differences (26.67% vs. 75.00% and 73.68% vs. 39.29%, P<0.05). Cox multivariate regression analysis result showed that clinical stage, IPI, SENP1 and SUMO1 were independent risk factors affecting the prognosis in patients with DLBCL ( HR = 1.352, 1.487, 2.048 and 3.295; 95% CI 1.180 to 1.691, 1.187 to 1.602, 2.536 to 4.023 and 2.752 to 5.325; P<0.05 or <0.01). Conclusions:In patients with DLBCL, SENP1 is highly expressed and SUMO1 is lowly expressed. The expression levels of SENP1 and SUMO1 are closely related to clinical stage and IPI in patients with DLBCL, and they are independent risk factors of the prognosis.
10.The predictive value of crescents in adult Henoch-Sch(o)lein purpura nephritis
Lili MA ; Xiaohan HUANG ; Pingping REN ; Liangliang CHEN ; Hongya WANG ; Haidongqin HAN ; Jianghua CHEN ; Fei HAN
Chinese Journal of Nephrology 2019;35(5):367-372
Objective To study the renal prognosis with the type and proportion of crescentic in adult Henoch Schonlein purpura nephritis (HSPN).Methods A total of 275 HSPN cases diagnosed in the First Affiliated Hospital of Zhejiang University were retrospectively analyzed.According to the pathological results,they were divided into four groups:99 patients in none crescent group (NC),35 patients in segmental crescents group (SC),122 patients with circumferential crescent <25% (C1),and 19 patients with circumferential crescent≥25% (C2).Renal prognostic events were defined as estimated glomerular filtration rate (eGFR) decreased by 30% over baseline within 2 years,doubling of serum creatinine or end-stage renal disease during follow-up.Kaplan-Meier survival analysis was used to compare the renal survival rate of each group.Univariate and multivariate Cox regression model was used to recognize the risk factor of poor renal outcome.Results There was no significant difference in age,extra renal organ performance and mean arterial pressure among groups.Among NC group,SC group,C1 group and C2 group,difference in serum creatinine (P=0.001),eGFR (P=0.003) and proteinuria levels (P < 0.001) were statistically significant.There was no significant difference in the ratio of global sclerosis,mesangial hypercellularity and interstitial inflammation/fibrosis among the groups.The patients were followed up for 86(58,116) months.The renal survival rates of NC group,SC group,C1 group and C2 group were 96%,100%,83.6% and 68.4% respectively.Kaplan-meier survival analysis showed significant differences (Log Rank=23.24,P< 0.001).Cox multivariate regression analysis indicated that presence of circumferential crescent (HR=3.59,95%CI 1.34-9.62,P=0.008) and low eGFR (HR=0.979,95% CI 0.968-0.989,P < 0.001) were independent prognostic factors.Conclusion The presence of circumferential crescent and low eGFR level are independent risk factors for poor renal prognosis in HSPN patients.