1.Clinical characteristics and treatment progress of adolescent and young adult with colorectal cancer
Hongkai YAN ; Chaoxu LIU ; Ning SONG ; Liubin SHI
Journal of International Oncology 2017;44(4):307-309
Colorectal cancer is one of the most common malignant tumors of digestive system.There are significant differences between young patients and other ages in aspects of the disease features, biological characteristics, risk factors, clinical treatment and prognosis, etc.And the analysis of young colorectal cancer patients′ characteristics can provide new ideas for clinical treatment.
2. Application of intravoxel incoherent motion sequence in evaluating and predicting response to neoadjuvant chemotherapy in esophageal squamous cell carcinoma
Tao SONG ; Hongkai ZHANG ; Hailiang LI ; Jianjun QIN ; Wen FENG ; Yan ZHAO ; Jinrong QU
Chinese Journal of Radiology 2018;52(8):581-586
Objective:
To assess intravoxel incoherent motion(IVIM) in evaluating and predicting response to neoadjuvant chemotherapy(NAC) in esophageal squamous cell carcinoma(ESCC).
Methods:
Forty-seven patients with ESCC diagnosed by pathological findings on biopsy from September 2015 to March 2017 were prospectively collected. All patients were examined before and after NAC using routine MRI scan and IVIM. The standard apparent diffusion coefficient (ADCstandard), diffusion coefficient (D), perfusion coefficient (D*) and perfusion score (f) were measured. The patients were divided into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) according to the 1.1 version of the response evaluation criteria in solid tumors (RECIST). Thirty-one patients underwent surgery after NAC, and the patients were divided into TRG 0-3 according to tumor regression grade (TRG). The differences of parameter values before and after NAC between different groups were analyzed using Student's
3.Predictive value of intravoxel incoherent motion imaging for pathologic response to neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma
Tao SONG ; Jinrong QU ; Hongkai ZHANG ; Jianjun QIN ; Wen FENG ; Yan ZHAO ; Hailiang LI
Chinese Journal of Digestive Surgery 2019;18(6):594-600
Objective To explore the predictive value of intravoxel incoherent motion (IVIM) imaging for the pathologic response to neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma (ESCC).Methods The prospective study was conducted.The clinicopathological data of 33 patients with locally advanced ESCC who were admitted to Affiliated Hospital of Zhengzhou University from September 2015 to October 2017 were collected.Patients received magnetic resonance imaging (MRI) and IVIM imaging examination before and after neoadjuvant chemotherapy.Two radiologists read the imaging together,manually delineated the region of interest in the diffusion-weighted imaging,and the apparent diffusion coefficient (ADC),diffusion coefficient (D),perfusion coefficient (D*),and perfusion score of the tumor (f) were automatically measured.Patients underwent neoadjuvant chemotherapy with paclitaxel plus cisplatin,and underwent radical surgery for esophageal cancer after 2 cycles of chemotherapy.Observation indicators:(1) comparison of IVIM imaging parameters before and after neoadjuvant chemotherapy in patients with ESCC;(2) comparison of change value and change rate of IVIM imaging parameters before and after neoadjuvant chemotherapy in patients with different tumor regression grade (TRG);(3) predictive efficacy of change value and change rate of IVIM imaging parameters before and after neoadjuvant chemotherapy for TRG.Measurement data with normal distribution were presented as Mean±SD,and comparison before and after neoadjuvant chemotherapy was done using the paired t test,and comparison between different TRG patients was done using the t test.Measurement data with skewed distribution were presented as M(P25,P75),and comparison before and after neoadjuvant chemotherapy and between different TRG patients were done using the Wilcoxon rank sum test.The receiver operating characteristic (ROC) curve was used to evaluate predictive value of IVIM imaging parameters.Results Thirty-three patients were screened for eligibility,including 26 males and 7 females,aged from 44 to 74 years,with an average age of 60 years.All the 33 patients were diagnosed as ESCC by pathological examination.(1) Comparison of IVIM parameters before and after neoadjuvant chemotherapy in patients with ESCC:33 patients with ESCC showed a significant difference in the ADC,D,and f value after neoadjuvant chemotherapy [ADC:(1.95±0.56) × 10-3 mm2/s vs.(2.54±0.50) × 10-3 mm2/s,t=-6.98;D:(1.26×10-3 mm2/s (0.81×10-3 mm2/s,2.44×10-3 mm2/s) vs.1.68×10-3 mm2/s (0.83×10-3 mm2/s,2.27×10-3 mm2/s),Z=-3.96;f:0.33%±0.14% vs.0.42%±0.15%,t=-3.13,P< 0.05].(2) Comparison of change value and change rate of IVIM imaging parameters before and after neoadjuvant chemotherapy in different TRG patients:of 33 patients,15 were in TRG 2 and 18 were in TRG 3.The ADC change value,ADC change rate,D change value,D change rate were (0.85±0.52)× 10-3 mm2/s,52.91%± 32.51%,0.64× 10-3 mm2/s (0.05× 10-3 mm2/s,1.41 × 10-3 mm2/s),48.20% (3.03%,16.95%) of TRG 2 patients,and (0.38±0.35)×10-3 mm2/s,21.94%±19.08%,0.26×10-3 mm2/s (-1.43×10-3 mm2/s,0.81× 10-3 mm2/s),20.18% (-58.61%,77.14%) of TRG 3 patients,respectively,with significant differences between two groups (t=3.09,3.41,Z=-3.04,-2.93,P<0.05).(3) Predictive efficacy of change value and change rate of IVIM imaging parameters before and after neoadjuvant chemotherapy for TRG:ROC curve analysis showed that ADC change value exhibited an area under curve (AUC) of 0.798,a sensitivity of 66.7% and a specificity of 94.4% in predicting TRG,when 0.86× 10-3 mm2/s was used as the cut-off value.With 43.3% as the cut-off value,ADC change rate had an AUC of 0.793,a sensitivity of 66.7% and a specificity of 88.9% in predicting TRG.With 0.35× 10-3 mm2/s as the cut-off value,D change value had an AUC of 0.809,a sensitivity of 73.3% and a specificity of 77.8% in predicting TRG.With 25.9% as the cut-off value,D change rate had an AUC of 0.800,a sensitivity of 80.0% and a specificity of 72.2% in predicting TRG.Conclusions The change value and change rate of ADC and D values before and after neoadjuvant chemotherapy are potential predictors of pathologic response in ESCC.The significantly increased ADC and D values after neoadjuvant chemotherapy are prone to good pathologic response.The change value and change rate of D values show a better predictive value for pathologic response to neoadjuvant chemotherapy in ESCC compared with those of ADC values.
4.Comparison of efficacy and safety of direct thrombectomy and bridging thrombectomy in the treat-ment of acute anterior circulation large vessel occlusion stroke under different collateral circulation statuses
Yu GAO ; Zi'ang LI ; Jian ZHANG ; Hanpeng LIU ; Ping ZHANG ; Ruifang YAN ; Junyan YUE ; Hongkai CUI
Journal of Xinxiang Medical College 2024;41(2):169-174,179
Objective To compare the safety and efficacy of direct thrombectomy versus bridging thrombectomy in the treatment of acute anterior circulation large vessel occlusion stroke under different collateral circulation statuses.Methods Totally 93 patients with acute anterior circulation ischemic stroke admitted to the First Affiliated Hospital of Xinxiang Medical University from September 2020 to March 2023 were selected as the research subjects.Patients were divided into direct throm-bectomy group(n=47)and bridging thrombectomy group(n=46)based on the type of thrombectomy.Patients in the direct thrombectomy group received direct intravascular thrombectomy,while patients in the bridging thrombectomy group received intravenous thrombolysis with alteplase combined with mechanical thrombectomy.According computed tomography angiography,the collateral circulation Tan classification was applied to divide the patients into good collateral circulation sub-group and poor collateral circulation sub-group.The modified thrombolysis in cerebral infarction grading(mTICI)was used to evaluate vessel recanalization.Head computed tomography plain scan was performed at 24-48 hours postoperatively to assess if there was hemorrhagic transformation,and modified Rankin Scale score was performed at 90 days postoperatively.Information such as imaging examination time,femoral artery puncture time,vessel recanalization time after thrombectomy,prognosis and spontaneous non-traumatic symptomatic intracerebral hemorrhage(SICH)were collected.Results The age,gender,baseline Alberta stroke program early computed tomography score,baseline national institutes of health stroke scale score,proportions of hypertension,diabetes and atrial fibrillation,baseline systolic pressure,creatinine,baseline blood glucose,platelet count,occlusion site,stroke etiologies and collateral circulation status of patients in the two groups were not statistically significantly different(P>0.05).There were no significant differences in the post-admission imaging examination time,femoral artery puncture time,vessel recanalization time after thrombectomy,successful vascular reperfusion rate,good prognosis rate,mortality rate,and SICH incidence between the two groups(P>0.05).The hemorrhagic transformation rate of patients in the direct thrombectomy group was significantly lower than that in the bridging thrombectomy group(P<0.05).There were no significant differences in the post-admission imaging examination time,femoral artery puncture time,vessel recanalization time after thrombectomy,successful vascular reperfusion rate,good prognosis rate,mortality rate,and SICH incidence between patients with good collateral circulation and patients with poor collateral circulation in the two groups(P>0.05).The hemorrhagic transformation rate of patients with good and poor collateral circulation in the direct thrombectomy group was significantly lower than that in the bridging thrombectomy group(P<0.05).Conclusion Under different collateral circulation conditions,the safety and efficacy of direct thrombectomy and bridging thrombectomy in the treatment of acute anterior circulation large vessel occlusion stroke are similar,but bridging thrombectomy is more likely to result in cerebral hemorrhage transformation compared with direct thrombectomy.
5.The value of 3 T MR in preoperative T staging of potentially resectable esophageal cancer compared withendoscopicultrasonography
Jia GUO ; Zhaoqi WANG ; Fengguang ZHANG ; Hongkai ZHANG ; Yanan LU ; Jianjun QIN ; Zhongxian ZHANG ; Ting ZHANG ; Shouning ZHANG ; Yafeng DONG ; Yin LI ; Yan ZHAO ; Hui LIU ; Xu YAN ; Nickel DOMINIK ; Hailiang LI ; Jinrong QU
Chinese Journal of Radiology 2018;52(3):199-203
Objective To evaluate the value of 3T magnetic resonance imaging (MRI) in the preoperative T staging of potentially resectable esophageal cancer(EC), compared with endoscopic ultrasonography (EUS). Methods Patients with resectable EC pathologically confirmed by biopsy from March 2015 to September 2016 were prospectively enrolled. All patients underwent MRI (including T2-TSE-BLADE,DWI and radial-VIBE)and EUS one week after the biopsy,and MRI were performed prior to EUS, both MRI and EUS were acquired within one week before surgery. Two readers with more than 5 years experiences in the MRI diagnosis evaluated the MR image quality using a 5-point score independently. T staging was assigned on MRI and EUS by the two MRI readers using double-blind method and one endoscopist in accordance with the 7th edition of AJCC TNM Classification for EC, and any disagreement between two MRI readers was resolved by consensus with discussion to the third senior MRI doctor. The inter-observer agreement between two MRI readers were calculated using Kappa test for image quality scores and T staging results. Considering postoperative pathological T staging results as the gold standard, the performances of MRI and EUS were evaluated based on the accuracy rate and analyzed by χ2 test. Results A total of 70 patients were enrolled in the study, the good image quality cases (≥ 3 scores) were 66 in reader 1 and 68 in reader 2. The inter-observer agreement of the image quality scores by two readers was excellent (Kappa=0.824, P<0.05). The pathological results revealed 16 cases of T1 stage, 18 cases of T2 stage, 30 cases of T3 stage, and 6 cases of T4a stage. The inter-observer agreement of the preoperative T staging of EC by two readers was excellent (Kappa=0.809, P<0.05). The accuracy rates of MRI and EUS for preoperative T staging of EC were 92.9% (65/70) and 67.1% (47/70), respectively, and the difference in accuracy rates of two techniques was statistically significant (χ2=14.5, P<0.05). Conclusions The accuracy rate of MRI for preoperative T staging of EC is significantly higher than that of EUS. MRI can be used as a noninvasive method for preoperative T staging of EC.
6.Correlation between quantitative parameters of dynamic contrast?enhanced MRI after neoadjuvant chemotherapy and pathological grades in esophageal squamous cell carcinoma
Yanan LU ; Hongkai ZHANG ; Zhaoqi WANG ; Ling MA ; Yan ZHAO ; Pengrui GAO ; Yingshu WANG ; Zhengyan JIA ; Shuang LU ; Hailiang LI ; Jianjun QIN ; Jinrong QU
Chinese Journal of Radiology 2019;53(7):573-578
Objective To investigate the correlation between quantitative parameters of dynamic contrast?enhanced MRI (DCE?MRI) after neoadjuvant chemotherapy and pathological grades in esophageal squamous cell carcinoma. Methods Fifty?six patients with esophageal squamous cell carcinoma who were confirmed by esophagoscope and received neoadjuvant chemotherapy before operation between September 2015 and December 2017 in the Affiliated Cancer Hospital of Zhengzhou University were prospectively analyzed, and MRI examination was performed within one week before operation. All patients underwent routine chest MRI and DCE?MRI scanning, and quantitative parameters of DCE?MRI, including volume transfer constant (Ktrans),exchange rate constant (Kep) and extravascular extracellular volume fraction (Ve) were measured. Pathological grading was assessed as highly differentiated, moderately differentiated, poorly differentiated,and undifferentiated. Intraclass correlation coefficient (ICC) was calculated from the results of two radiologists. Kruskal?Wallis H test was used to compare the differences of quantitative parameters between different pathological grade groups of DCE?MRI,and Mann?Whitney U test was utilized to compare the intraclass differences among pathological grades. Spearman rank correlation analysis was performed for evaluating the correlation between DCE?MRI parameters and pathological grade of esophageal squamous cell carcinoma. The receiver operating characteristic (ROC) curves were used to evaluate the diagnosis accuracy of different DCE?MRI parameters in pathological grade of esophageal squamous cell carcinoma after neoadjuvant chemotherapy. Results The 56 patients were divided into four groups according to pathological findings: well differentiated group (n=8), moderately differentiated group (n=39), poorly differentiated group (n=9) and undifferentiated group (n=0). The differences of Ktransmean,Ktrans75%,Kepmax, Kepmean,Kep75% between different pathological grading groups were statistically significant (all P<0.05),and these parameters showed positive correlation significantly with pathological grading (r values were 0.778, 0.632, 0.594, 0.725, 0.489 respectively, all P<0.05). The ROC curve area of Ktransmean, Ktrans75% in the diagnosis of pathological grade for esophageal squamous cell carcinoma was 0.750,0.856,respectively. The diagnostic efficiency of Ktrans75% was the best with the diagnostic threshold of 0.693/min,sensitivity of 87.5%, specificity of 78.5%, respectively. Conclusion The quantitative parameters of DCE?MRI after neoadjuvant chemotherapy in esophageal squamous cell carcinoma have the potential value for predicting pathological grade.
7.Mechanism of Yitangkang in Improving Apoptosis of Skeletal Muscle Cells by Inhibiting AGE/RAGE Signaling Pathway
Jiaxiang YU ; Hanwen ZHANG ; Lie WANG ; Yan SHI ; Rui YU ; Jianyu DAI ; Chao QU ; Xiande MA ; Xueying HAN ; Zhimin WANG ; Jiren AN ; Yuefeng CHENG ; Hongkai JI ; Wenshun ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(13):54-64
ObjectiveTo determine the mechanism of Yitangkang in correcting excessive apoptosis of skeletal muscle cells to improve insulin resistance (IR) by inhibiting the advanced glycation end product (AGE)/receptor for the advanced glycation end product (RAGE) signaling pathway. Method① In vitro experiments. Yitangkang-medicated serum was prepared. C2C12 cells were divided into a blank group, a model group, high-, medium-, and low-dose Yitangkang-medicated serum groups (40, 20, and 10 g·kg-1), and a RAGE inhibitor group. The IR model was induced by palmitic acid in C2C12 cells except for those in the blank group. After the corresponding intervention methods were conducted,the cell viability and glucose consumption level of each group were determined. In addition,the apoptosis rate was determined using flow cytometry. The mRNA and protein expression levels of the important apoptotic proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), p53, cysteinyl aspartate-specific protease-3 (Caspase-3), and cysteinyl aspartate-specific protease-9 (Caspase-9)] were determined using Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot. ② In vivo experiments. Ninety-six eligible Wistar rats were divided into a blank group, a model group, high-,medium-,and low-dose Yitangkang groups (40, 20, and 10 g·kg-1), and a western medicine group (pioglitazone hydrochloride,1.35 mg·kg-1). The IR model was induced using high-glucose and high-fat feed for diabetes combined with intraperitoneal injection of low-dose streptozotocin (STZ) in animals and verified by the hyperinsulinemic-euglycemic clamp (HEC) test. After the model was determined successfully, the rats in each group were given intragastric administration of drugs as required. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to determine the number of positive apoptotic cells in the skeletal muscle tissues of rats in each group,while Real-time polymerase chain reaction(Real-time PCR) and Western blot were performed to determine the mRNA and protein expression levels of the important apoptotic proteins Bcl-2, Bax, p53, Caspase-3, and Caspase-9. Result① In vitro experiments. compared with the blank group, the model groups showed increased apoptosis rate of C2C12 cells and decreased cell viability and glucose consumption (P<0.01). Compared with the model group, the Yitangkang-medicated serum groups and the RAGE inhibitor group showed decreased apoptosis rate of C2C12 cells and increased cell viability and glucose consumption (P<0.01). Compared with the blank group, the model group showed decreased expression levels of Bcl-2 mRNA and protein in C2C12 cells and increased mRNA and protein expression levels of Bax, p53, Caspase-3, and Caspase-9 (P<0.01). Compared with the model group, the Yitangkang-medicated serum groups and the RAGE inhibitor group showed increased expression levels of Bcl-2 mRNA and protein in C2C12 cells (P<0.01) and decreased mRNA and protein expression levels of Bax, p53, Caspase-3, and Caspase-9 (P<0.05, P<0.01). ② In vivo experiments. The number of positive apoptotic cells in the skeletal muscle tissues of rats in the model group significantly increased as compared with that in the blank group (P<0.01). The number of positive apoptotic cells in the skeletal muscle tissues of rats in the Yitangkang groups and the western medicine group decreased as compared with that in the model group (P<0.01). Compared with the blank group, the model group showed decreased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats and increased mRNA and protein expression levels of Bax, p53, Caspase-3, and Caspase-9 (P<0.01). Compared with the model group, the Yitangkang groups and the western medicine group showed increased expression levels of Bcl-2 mRNA and protein in skeletal muscle tissues of rats (P<0.01) and decreased mRNA and protein expression levels of Bax, p53, Caspase-3, and Caspase-9 (P<0.05, P<0.01). The medium-dose Yitangkang showed a similar effect as RAGE inhibitor, and the effect was equivalent to that of pioglitazone hydrochloride. ConclusionYitangkang can inhibit skeletal muscle cell apoptosis by inhibiting the AGE/RAGE signaling pathway.
8.PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism.
Mingming SUN ; Leilei LI ; Yujia NIU ; Yingzhi WANG ; Qi YAN ; Fei XIE ; Yaya QIAO ; Jiaqi SONG ; Huanran SUN ; Zhen LI ; Sizhen LAI ; Hongkai CHANG ; Han ZHANG ; Jiyan WANG ; Chenxin YANG ; Huifang ZHAO ; Junzhen TAN ; Yanping LI ; Shuangping LIU ; Bin LU ; Min LIU ; Guangyao KONG ; Yujun ZHAO ; Chunze ZHANG ; Shu-Hai LIN ; Cheng LUO ; Shuai ZHANG ; Changliang SHAN
Acta Pharmaceutica Sinica B 2023;13(1):157-173
Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.