1.PARP1 promotes the progression of hepatocellular carcinoma by regulating expression of POU2F2
Ziqiang WEN ; Junliang LAN ; Bo ZHOU ; Qiwei XU
China Oncology 2024;34(9):848-856
Background and purpose:Hepatocellular carcinoma(HCC)is a major disease seriously threatening human health.Poly(ADP-ribose)polymerase-1(PARP1)is an enzyme that catalyzes poly ADP-ribosylation.Given the role of PARP1 in DNA damage repair,it is generally considered as an oncogene.However,the expression of PARP1 and its mechanism in HCC are not yet clear.This study aimed to investigate the role of PARP1 in the occurrence and development of HCC and its potential mechanisms.Methods:First,we analyzed the expression pattern of PARP1 in The Cancer Genome Atlas(TCGA)and Clinical Proteomic Tumor Analysis Consortium(CPTAC)HCC database,and identified the expression trend of PARP1 in our HCC cohort using real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR)and Western blot.Then,the enzyme activity of PARP1 was inhibited by PJ34,an inhibitor of PARP1 and the expression of PARP1 in HCC cell lines was downregulated with small RNA interference technology.Based on these models,the following experiments were conducted:First,the effect of PARP1 on cell viability was assessed by cell counting kit-8(CCK-8)assay and flow cytometry;Second,the expression levels of stemness-related genes in HCC cells were identified using RTFQ-PCR;Third,the effect of inhibition of PARP1 on migration and invasion of HCC cells was detected by migration and invasion assay(transwell assay).Finally,bioinformatic analysis was performed to identify new target genes and the pathways regulated by PARP1 in HCC progression.Rescue experiments were performed to determine whether PARP1 target genes were involved in the malignant phenotypes of HCC cells.Results:The expression of PARP1 was significantly up-regulated in HCC tissues in both TCGA and CPTAC database.RTFQ-PCR and Western blot assays showed that PARP1 was obviously up-regulated in HCC tissues compared to paracancerous tissues.Survival analysis showed that PARP1 expression was significantly negatively correlated with the prognosis of patients.The results of CCK-8,flow cytometry,RTFQ-PCR and transwell assay indicated that inhibition of PARP1 attenuated proliferation and activity of HCC cells,as well as weakened their stemness,migration and invasion.Bioinformatics analysis suggested that PARP1-regulated genes were enriched in the nuclear factor-κB(NF-κB)and necroptosis pathways,with POU class homeobox 2(POU2F2)potentially being a target gene of PARP1.Correlation analysis,along with RTFQ-PCR and Western blot detection,confirmed that the expression of POU2F2 was regulated by PARP1,while not affected by PJ34,indicating the effect of nonenzymatic function of PARP1 on POU2F2.CCK-8,flow cytometry and RTFQ-PCR results showed that the reintroduction of POU2F2 enhanced proliferative capacity,increased activity,and promoted stemness of HCC cell lines with PARP1 knockdown.Conclusion:By positively regulating the expression of POU2F2,PARP1 promotes malignant phenotypes of HCC cells,providing new insights for clinical treatment and drug development for HCC.
2.The influence of depth of invasion on the prognosis of patients with pT1 mid-thoracic esophageal cancer undergoing left thoracotomy
Shuguang LI ; Jingyuan WEN ; Shiwang WEN ; Ziqiang TIAN ; Shuchai ZHU ; Wenbin SHEN
Chinese Journal of Thoracic and Cardiovascular Surgery 2023;39(11):653-659
Objective:To investigate the influence of the depth of invasion on the prognosis of pT1 stage mid-thoracic esophageal cancer patients undergoing left thoracotomy.Methods:Retrospectively analyze the clinicopathological data of 139 patients with pT1N0M0 stage of mid-thoracic esophageal cancer who meet the enrollment criteria. Firstly, the prognosis and influencing factors of the whole group were analyzed. The differences in prognosis, local recurrence and distant metastasis between PT1A and PT1B patients were compared, and the influence of different infiltration depth on prognosis and treatment failure of patients was analyzed. SPSS 19.0 statistical software was used for statistical analysis.Results:The 1-year, 3-year and 5-year overall survival(OS) and disease-free survival(DFS) were 95.0%, 87.8%, 82.0% and 91.4%, 84.2%, 77.0%, respectively. There were significant differences in OS( χ2=7.500, P=0.006) and DFS( χ2=7.354, P=0.007) at 1, 3 and 5 years between pT1a and pT1b patients. Cox multivariate analysis showed that pT stage and pathological type were independent prognostic factors for OS and DFS( P<0.05). There were no significant differences in OS( χ2=0.734, P=0.693) and DFS( χ2=0.7690, P=0.681) of pT1a tumors with different invasion depths. There were significant differences in OS( χ2=15.368, P<0.001) and DFS( χ2=27.470, P<0.001) at 1, 3 and 5 years of pT1b tumors with different invasion depths. The recurrence rate of pT1b(23.8%) was significantly higher than that of pT1a(5.3%)( χ2=5.274, P=0.022). The distant metastasis rate of the former(10.9%) was also significantly higher than that of the latter(0)( χ2=4.494, P=0.034). There were significant differences in local recurrence rate( χ2=17.051, P<0.001) and distant metastasis rate( χ2=15.460, P<0.001) among pT1b patients with different infiltration depths. Logistic multivariate analysis showed that the depth of infiltration was an independent factor affecting the occurrence of local recurrence in stage pT1b patients after treatment( P<0.001). Pathological type( P=0.003) and infiltration depth( P=0.027) were independent factors affecting the occurrence of distant metastasis. Conclusion:pT1a period and pT1b period after the prognosis and treatment of patients with different failure modes, and pT1b period in patients with different infiltration depth and the prognosis of patients and its failure mode after treatment significantly related, infiltration depth of pT1b period after treatment in patients with the independence of the influencing factors of failure, suggest that clinical doctors should pay attention to pT1b period in patients with postoperative adjuvant therapy. This conclusion needs to be confirmed by large prospective studies of cases.
3.Comparisons of minimally invasive esophagectomy and open esophagectomy in lymph node metastasis/dissection for thoracic esophageal cancer
Zhenhua LI ; Chunyue GAI ; Yuefeng ZHANG ; Shiwang WEN ; Huilai LV ; Yanzhao XU ; Chao HUANG ; Bo ZHAO ; Ziqiang TIAN
Chinese Medical Journal 2022;135(20):2446-2452
Background::The study aimed to clarify the characteristics of lymph node metastasis (LNM) and to compare the oncologic outcomes of minimally invasive esophagectomy (MIE) with open esophagectomy (OE) in terms of lymph node dissection (LND) in thoracic esophageal cancer patients.Methods::The data from esophageal cancer patients who underwent MIE or OE from January 2016 to January 2019 were retrospectively reviewed. The characteristics of LNM in thoracic esophageal cancer were discussed, and the differences in numbers of LND, LND rate, and LNM rate/degree of upper mediastinum between MIE and OE were compared.Results::For overall characteristics of LNM in 249 included patients, the highest rate of LNM was found in upper mediastinum, while LNM rate in middle and lower mediastinum, and abdomen increased with the tumor site moving down. The patients were divided into MIE ( n = 204) and OE groups ( n = 45). In terms of number of LND, there were significant differences in upper mediastinum between MIE and OE groups (8 [5, 11] vs. 5 [3, 8], P < 0.001). The comparative analysis of regional lymph node showed there was no significant difference except the subgroup of upper mediastinal 2L and 4L group (3 [1, 5] vs. 0 [0, 2], P < 0.001 and 0 [0, 2] vs. 0, P = 0.012, respectively). Meanwhile, there was no significant difference in terms of LND rate except 2L (89.7% [183/204] vs. 71.1% [32/45], P = 0.001) and 4L (41.2% [84/204] vs. 22.2% [10/45], P = 0.018) groups. For LNM rate of T3 stage, there was no significant difference between MIE and OE groups, and the comparative analysis of regional lymph node showed that there was no significant difference except 2L group (11.1% [5/45] vs. 38.1% [8/21], P = 0.025). The LNM degree of OE group was significantly higher than that of MIE group (27.2% [47/173] vs. 7.6% [32/419], P < 0.001), and the comparative analysis of regional LNM degree showed that there was no significant difference except 2L (34.7% [17/49] vs. 7.7% [13/169], P < 0.001) and 4L (23.8% [5/21] vs. 3.9% [2/51], P= 0.031) subgroups. Conclusion::MIE may have an advantage in LND of upper mediastinum 2L and 4L groups, while it was similar to OE in other stations of LND.
4.Reasons for Conversion to Thoracotomy in 83 Cases during Video-assisted Thoracic Surgery Lobectomy: A Summary of 1,350 Consecutive Operations by A Single Surgical Team.
Peng SU ; Shiwang WEN ; Mingbo WANG ; Yanzhao XU ; Huilai LV ; Zhenhua LI ; Ziqiang TIAN
Chinese Journal of Lung Cancer 2021;24(7):475-482
BACKGROUND:
Video assisted thoracic surgery (VATS) is the main surgical method for lung cancer. The aim of this study was to analyze the reasons for conversion to thoracotomy in 83 cases among 1,350 consecutive cases who underwent video-assisted thoracic surgery (VATS) lobectomy by a single surgical team, in order to achieve a deeper understanding of the rules and the opportunity for conversion to thoracotomy in VATS lobectomy under normal conditions.
METHODS:
The clinical data of 1,350 patients who underwent VATS lobectomy between September 21, 2009 and June 1, 2020, by a single surgical team in the Fifth Department of Thoracic Surgery of the Fourth Hospital of Hebei Medical University were retrospectively analyzed. There were 773 males and 577 females, aged 8-87 years, with a median age of 61.3 years, including 83 cases of benign diseases, 38 cases of lung metastases, and 1,229 cases of primary lung cancer. The cases with stage I, II and IIIa were 676, 323 and 230, respectively. The cases of left upper, left lower, right upper, right middle, right lower, right middle and upper and right middle and lower lobectomy were 301 (22.30%), 231 (17.11%), 378 (28.00%), 119 (8.81%), 262 (19.41%), 16 (1.19%) and 43 (3.19%), respectively.
RESULTS:
In the cohort of 1,350 consecutive patients with VATS lobectomy, 83 patients (6.15%) were converted to thoracotomy for different reasons. The conversion rate of benign lesions was significantly higher than that of malignant tumors (P<0.05). The conversion rate in stage IIIa was significantly higher than that in stage I and II (P<0.05). The conversion rate of combined lobectomy was significantly higher than that of single lobectomy (P=0.001). The conversion rate of left upper lobectomy was significantly higher than that of other single lobectomy (P<0.001). The conversion rate of right middle lobectomy was significantly lower than that of other single lobectomy (P=0.049). The main reasons for conversion were vascular injury (38.55%), lymph node interference (26.51%) and dense adhesion in thoracic cavity (16.87%). In the conversion group, the total operation time was (236.99±66.50) min and the total blood loss was (395.85±306.38) mL. The operation time in patients converted to thoracotomy due to lymph node interference was (322.50±22.68) min, which was significantly longer than that in the other groups (P<0.05). The intraoperative blood loss in patients converted to thoracotomy due to vascular injury was (560.94±361.84) mL, which was significantly higher than that in the other groups (P<0.05). With the increase in surgical experience, the number of vascular injuries gradually decreased at the early stage, mid-stage and late stage (P=0.045).
CONCLUSIONS
In VATS lobectomy, benign lung lesions and more advanced malignant tumors led to more surgical difficulties and higher conversion rate. The conversion rate was different in different lobectomy sites, with the highest in left upper lobectomy, and the lowest in right middle lobectomy. Vascular injury, lymph node interference and dense adhesion were the main reasons for conversion to thoracotomy, which led to prolonged operation time and increased blood loss. With the increasing number of surgical cases, the rate of conversion to thoracotomy in VATS lobectomy continues to decline, which may be mainly due to the more advanced treatment of pulmonary vessels.
5.Value of dual-layer spectral detector CT in diagnosing regional lymph node metastasis of colorectal cancer
Yan CHEN ; Ziqiang WEN ; Yuru MA ; Yiyan LIU ; Yutao QUE ; Shenping YU
Chinese Journal of Radiology 2021;55(12):1253-1258
Objective:To investigate the value of quantitative parameters derived from dual-layer spectral detector CT (SDCT) in characterizing regional lymph node (LN) status of colorectal cancer.Methods:From August 2019 to May 2020, 101 patients with colorectal cancer confirmed by pathology in the First Affiliated Hospital of Sun Yat-sen University were retrospectively collected. The largest regional LNs were matched with surgical pathology one by one and divided into metastatic LNs group (42 cases) and nonmetastatic LNs group (59 cases) according to pathological results. Based on preoperative venous phase contrast enhanced SDCT images he short-axis diameter (S) and the of the largest regional LN was measured, then its border and enhancement homogeneity were evaluated. Outlining the ROI along the edge of the LN on its widest cross section, the iodine density (ID) and effective atomic number (Z eff) were measured, then the normalized ID (nID) and normalized Z eff (nZ eff) were calculated. The χ 2 test, Fisher′s exact test, independent samples t-test or Mann-Whitney U test were used to compare the differences of each parameter between pathologically metastatic and nonmetastatic LNs and a logistic regression model was constructed. The ROC curves and area under the curve (AUC) were performed to evaluate the diagnostic performance of each parameter. DeLong test was used to compare the differences of each AUC. Results:The S, border, enhancement homogeneity, ID, Z eff, nID and nZ eff of LNs all showed significant differences between metastatic and nonmetastatic LNs (all P<0.001). The regression model constructed by S and Z eff of LNs had the highest value in differentiating metastatic and nonmetastatic LNs, with an AUC of 0.935, sensitivity and specificity of 85.7% and 89.8%, respectively. Its diagnostic value was higher than that of S, border, enhancement homogeneity (AUC 0.674-0.832, all P<0.05) and SDCT quantitative parameters (AUC 0.863-0.906, all P<0.05) of LNs. Conclusion:SDCT quantitative parameters facilitate the accurate diagnosis of regional metastatic LNs in patients with colorectal cancer, among which the multi-parameter regression model has the highest diagnostic value.
6.Surgical treatment of deep brain stimulation for pediatric hereditary dystonia
Haibo YANG ; Ziqiang CAO ; Xinhua BAO ; Yongxin WEN ; Hongxin YAO
Chinese Journal of Applied Clinical Pediatrics 2020;35(9):662-666
In the past 30 years, with the advancement of functional neurosurgery, neuroelectrophysiology and neuroimaging, deep brain stimulation (DBS), as a new tool for the treatment of dyskinesia, has been considered to have underwent the fastest development in this field.Many patients with dyskinesias have significantly improved their main clinical symptoms after treatment with DBS, some of the improvement are even dramatic.Due to its minimally invasive characteristics, reversibility and adjustability, DBS therapy has been increasingly used in the treatment of dystonia in children.Hereditary dystonia is the most common type of dyskinesia in children, and there is no effective treatment yet.Recently, some dyskinesia at home and abroad centers have carried out DBS treatment for pediatric hereditary dystonia and achieved some encouraging results.Now, the effect of DBS in the treatment of hereditary dystonia in children and the main process of DBS treatment were mainly discussed, and shared the experience based on the clinical practices of Multidisciplinary Collaborative Diagnosis and Treatment Center for Children′s Motor Disorders, Peking University First Hospital.
7.A retrospective comparison of thoracoscopic and laparoscopic esophagectomy between right neck anastomosis and left neck anastomosis.
Yanzhao XU ; Xinqiang SHI ; Jingge CHENG ; Yuefeng ZHANG ; Shiwang WEN ; Zhenhua LI ; Huilai LVY ; Ziqiang TIAN
Chinese Journal of Gastrointestinal Surgery 2018;21(9):1008-1012
OBJECTIVETo evaluate the feasibility of right neck anastomosis in thoracoscopic and laparoscopic esophagectomy.
METHODSThis study used a retrospective cohort study method. Clinical data of 169 patients with stage I-III esophageal squamous cell carcinoma undergoing neck anastomosis in thoracoscopic and laparoscopic esophagectomy at the Department 5 of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from November 2013 to October 2016 were retrospectively analyzed. Eighty-two cases underwent right neck anastomosis (right neck anastomosis group) and 87 cases underwent left neck anastomosis(left neck anastomosis group). Both groups underwent routine thoracoscopic and laparoscopic radical resection of esophageal cancer. The entry of right and left neck anastomosis group was at the anterior edge of the right and left sternocleidomastoid muscle respectively. Anastomosis of the esophagogastric junction was performed and the drainage tube was placed in the neck incision. The operation time, intraoperative blood loss, lymph node dissection and morbidity of postoperative complications were compared between the two groups.
RESULTSThere were 101 males and 68 females among 169 patients with esophageal cancer. There were no significant differences in age, gender, tumor location, clinical stage between two groups(all P>0.05). The total operation time of left and right neck anastomosis groups was (278.3±39.4) minutes and (287.8±39.4) minutes, respectively (t=1.563, P=0.120). The intraoperative blood loss was (134.9±71.5) ml and(147.9±85.5) ml, respectively (t=1.074, P=0.284). The number of lymph node dissections was (17.45±5.68) and (16.47±4.98), respectively (t=1.190, P=0.236). Seventeen cases(20.7%) in the right neck anastomosis group developed postoperative complications, while 31 cases (35.6%) in the left neck anastomosis group developed postoperative complications (χ²=4.609,P=0.032). Compared with left neck anastomosis group, right neck anastomosis group had lower rate of gastric emptying disorder (0% vs. 6.9%, P=0.029), anastomotic fistula (7.3% vs. 18.4%, χ²=4.572, P=0.033), pneumonia (18.3% vs. 32.2%, χ²=4.294, P=0.038) and ICU management (4.9% vs. 16.1%, χ²=4.726, P=0.030).
CONCLUSIONThoracoscopic and laparoscopic esophagectomy with right neck anastomosis is safe and effective, can completely remove the tumor, at the same time, has less complications than left neck anastomosis, and improve the quality of life.
Anastomosis, Surgical ; Esophageal Neoplasms ; surgery ; Esophagectomy ; Female ; Humans ; Laparoscopy ; Lymph Node Excision ; Male ; Postoperative Complications ; Quality of Life ; Retrospective Studies ; Thoracoscopy
8.Effects of early enteral immunonutrition on short-term quality of life and clinical outcome in patients with totally endoscopic esophagectomy
Yanzhao XU ; Ruixia GUO ; Yuefeng ZHANG ; Shiwang WEN ; Huilai LV ; Yonggang ZHU ; Peng SU ; Ziqiang TIAN
Chongqing Medicine 2018;47(11):1465-1469,1474
Objective To analysis the short-term quality of life and clinical outcome of early enteral immunonutrition(EIN)used after operation in patients with totally endoscopic esophagectomy.Methods This randomized controlled trial enrolled 110 patients receiving totally endoscopic esophagectomy in department of thoracic surgery of the fourth hospital of Hebei medical university between May 2015 and November 2016.The patients were randomly divided into enteral immunonutrition group (EIN group,n =56) and parenteral nutrition group (PN group,n=54).The scale scores of quality of life,the time of first postoperative anal exhaust,the time of removal of drainage tube,the number of postoperative infections and the length of hospitalization were compared between the two groups before operation and after operation.Results (1) There were no significant differences in age,gender,education,marital status,tumor location,clinical stage,intraoperative bleeding between the two groups (P>0.05).(2) There were no significant differences in the quality of life before operation (P>0.05);All functional scale scores of EIN group were significantly higher than PN group (P<0.05),while the symptom scale score were significantly lower than PN group(P<0.05).(3) There were significant differences in the time of first postoperative anal exhaust,the time of removal of drainage tube,the number of postoperative pneumonia compliCations and the length ofhospitalization in the two groups (P< 0.05).There was no significant difference in the incidence of anastomotic fistula between the two groups(x2=0.621,P=0.431 4) The scale scores of quality of life (the overall health status as the representative) had a negatively linear relationship with the clinical outcome(P =0.000),the absolute value of correlation coefficient in EIN group was higher than that in PN group.The higher score of the quality of life,the shorter time of the postoperative anal exhaust,removal of drainage tube and the length of hospitalization.Conclusion Enteral immunonutrition can improve the quality of life,improve the prognosis and promote the rapid recovery of patients with totally endoscopic esophagectomy.
9.Repeatability and consistency of intravoxel incoherent motion parameters of rectal cancers
Baolan LU ; Xiaojuan XIAO ; Xinyue YANG ; Yan CHEN ; Ziqiang WEN ; Shenping YU
Chinese Journal of Medical Imaging Technology 2018;34(4):568-572
Objective To explore the repeatability and consistency of MR intravoxel incoherent motion (IVIM) parameters of rectal cancers.Methods Routine high resolution rectal MR and IVIM sequence were performed on 128 patients with pathologically proved rectal cancers before treatment.IVIM maps were generated from two sets of b-values (group A:0,5,10,20,30,40,60,80,100,150,200,400,600 and 1000 s/mm2;group B:0,5,10,20,30,40,60,80,100,150,200,400,600,1000,1500 and 2000 s/mm2),and IVIM parameters (D,D* and f) were measured.Then IVIM parameters were measured again by the same observer three months later.The intra-class correlation coefficient (ICC) and Bland-Altman graph analysis were performed to explore the repeatability and consistency of IVIM parameters.Results The differences of IVIM parameters (D,D* and f) derived from the two sets of b-values were statistically different (all P<0.001).ICC and 95% confidence interval (CI) of D,D* and f was 0.968 (0.955,0.977),0.780 (0.688,0.845) and 0.957 (0.934,0.970),respectively.Bland-Altman analysis showed that the 95 % limits of agreement of D,D* and f was (10.8%,22.4%),(14.8%,61.9%) and (-45.3%,-10.2%),respectively.There was significant difference of D* between twice measurement by the same observer (P=0.001);ICC and 95%CI of D,D* and f was 0.826(0.670,0.908),0.678 (0.392,0.830) and 0.910 (0.830,0.952),respectively.Furthermore,Bland-Altman analysis showed that the 95% limits of agreement of D,D* and f were (-15.3%,12.4%),(-39.6%,61.2%) and (-22.6%,22.9%),respectively.Conclusion Under the two different sets of b-values,all IVIM parameters of rectal cancers demonstrate good consistency.In addition,D and f value show good repeatability.
10.Clinical Observation of Taxol Combined with Cisplatin Neoadjuvant Chemotherapy in the Treatment of Esophageal Cancer
Huilai LYU ; Li ZHANG ; Shiwang WEN ; Yuefeng ZHANG ; Yong LI ; Ziqiang TIAN
China Pharmacy 2016;27(18):2500-2502
OBJECTIVE:To observe the clinical efficacy of taxol combined with cisplatin neoadjuvant chemotherapy in the treatment of esophageal cancer and effects on serum tumor markers in patients with esophageal cancer. METHODS:100 patients with esophageal cancer were randomly divided into control group(50 cases) and observation group(50 cases). Observation group was given taxol+Cisplatin injection(TP)neoadjuvant chemotherapy,given 175 mg/m2 taxol by intravenous infusion,d1-5. And ev-ery 5 d was a treatment course,the regimen was adjusted based on patients’efficacy;control group was given conventional sur-gery and TP after surgery,the same usage and dosage as observation group,it lasted for 4 courses. Clinical efficacy,high mobility protein B1(HMGB1),carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) level in 2 groups before and after treatment were observed,objective response rate,disease control rate,the incidence of toxicity and severe toxicity,inci-dence of postoperative complications and survival rate of postoperative 1,3 and 5 years were recorded. RESULTS:After treatment, objective response rate in observation group was significantly higher than control group,HMGB1,CEA and SCC-Ag levels were significantly lower than before and control group,HMGB1 and CEA levels in control group were significantly lower than before, the differences were statistically significant(P<0.05);there were no significant differences in the disease control rate,chemothera-py-related toxicity,severe toxicity,incidence of postoperative complications,survival rate of postoperative 1,3 and 5 years and the median survival time between 2 groups(P>0.05). CONCLUSIONS:Taxol combined with cisplatin neoadjuvant chemotherapy can significantly improve the efficacy of patients with esophageal cancer and reduce the levels of cancer-related indicators,with good safety.

Result Analysis
Print
Save
E-mail