1.Knockdown of miR-296-5p alleviates nerve function damage after cere-bral infarction by activating ACE2 signaling pathway
Jibo LI ; Duanou XIAO ; Bin HE ; Feng XU ; Yongwen FENG
Chinese Journal of Pathophysiology 2024;40(8):1455-1462
AIM:To explore the effect of microRNA-296-5p(miR-296-5p)on neurological damage after cere-bral infarction(CI)and its regulatory relationship with angiotensin-converting enzyme 2(ACE2)signaling pathway medi-ated proliferation of endothelial progenitor cell(EPC).METHODS:Serum samples from 70 patients diagnosed with CI and accompanied by neurological damage in our hospital(CI group)and 70 healthy volunteers(healthy group)were se-lected.The mRNA expression of miR-296-5p,ACE2,and Mas in the serum of both groups were detected by RT-qPCR.The rat model of CI was constructed and SD rats were randomly divided into healthy control group,model control group,sh-miR-296-5p group,and ACE2 overexpression group(OE-ACE2 group).Neurological severity scores(NSS)score was evaluated.The CI status of rats in each group was observed by TTC staining.The mRNA expression of miR-296-5p,ACE2,and Mas in serum of rat was detected by RT-qPCR.EPC were isolated and cultured routinely,and were randomly divided into control group,sh-miR-296-5p group,OE-ACE2 group,OE-miR-296-5p+OE-ACE2 group,and sh-miR-296-5p+sh-ACE2 group.The viability of EPC was detected by CCK-8.Apoptosis of EPC was detected by flow cytometry.The mRNA expression of miR-296-5p,ACE2,and Mas in EPC was detected by RT-qPCR.The relationship between miR-296-5p and ACE2 was verified by dual luciferase reporter gene assay.RESULTS:(1)Clinical trial:compared with the healthy group,the level of miR-296-5p in serum of CI patients was obviously increased(P<0.05),while the mRNA ex-pression levels of ACE2 and Mas were obviously reduced(P<0.05).(2)Animal experiments:compared with the healthy control group,the NSS score,CI area,the level of miR-296-5p in serum,and the mRNA expression level of Mas in the model control group were obviously increased(P<0.05),while the mRNA expression level of ACE2 was obviously de-creased(P<0.05).Compared with the model control group,the NSS score,CI area,the level of miR-296-5p in serum,and the mRNA expression level of Mas in the sh-miR-296-5p group and OE-ACE2 group were obviously reduced(P<0.05),while the mRNA expression level of the ACE2 was obviously increased(P<0.05).(3)Cell experiment:Com-pared with the control group,the A450 and the level of miR-296-5p of EPC cells in the sh-miR-296-5p group and OE-ACE2 group were obviously reduced(P<0.05),the apoptosis rate,the mRNA expression level of ACE2,and Mas were obvious-ly increased(P<0.05).Compared with the sh-miR-296-5p group,the A450 and the level of miR-296-5p in the sh-miR-296-5p+sh-ACE2 group were obviously increased(P<0.05),the apoptosis rate,the mRNA expression level of ACE2,and Mas were obviously reduced(P<0.05).Compared with the OE-ACE2 group,the level of A450 and miR-296-5p in OE-miR-296-5p+OE-ACE2 group were obviously increased(P<0.05),the apoptosis rate,the mRNA expression level of ACE2,and Mas were obviously reduced(P<0.05).CONCLUSION:Knockdown of miR-296-5p may inhibit EPC proliferation by mediating the ACE2 signaling pathway,and alleviate neurological damage after CI.
2.Effect of atractylenolide Ⅲ on stroke in spontaneously hypertensive rats and its mechanism
Jibo LI ; Yongwen FENG ; Wenfeng WU ; Xuezheng FAN ; Haixia LI
Journal of Clinical Medicine in Practice 2023;27(22):71-76
Objective To investigate the effect of atractylenolide Ⅲ(A Ⅲ)on stroke in spon-taneously hypertensive rats by regulating microRNA-296-5p(miR-296-5p)expression.Methods The spontaneously hypertensive rats(SHR)were given 0.9%sodium chloride solution freely for 2 months,and then fed with 1%sodium chloride solution to establish the stroke model of SHR.The rat models were randomly grouped into Model group,A Ⅲ low-dose group(A Ⅲ-L group),A Ⅲ high-dose group(A Ⅲ-H group),positive drug nimodipine group(Nim group),miR-296-5p agonist group(miR-296-5p agomir group),agomir NC group,A Ⅲ-H+miR-296-5p agomir group,and A Ⅲ-H+agomir NC group,with 12 in each group.The changes in neurological symptom scores,av-erage arterial pressure,survival time,and platelet adhesion rate were detected and recorded;hema-toxylin and eosin(HE)staining was applied to detect pathological changes in the CA1 region of the rat hippocampus;quantitative reverse transcription polymerase chain reaction(qRT-PCR)was ap-plied to detect the expression of miR-296-5p in the hippocampal CA1 region.Results Compared with the NC group,the Model group showed increases in neurological symptom score,mean arterial pressure,platelet adhesion rate,miR-296-5p expression,shortened survival time,and severe pathological damage to the hippocampal CA1 area(P<0.05);compared with the Model group,the neurological symptom scores,mean arterial pressure,platelet adhesion rate,and miR-296-5p expression in the A Ⅲ-L,A Ⅲ-H,and Nim groups decreased,the survival time was prolonged,and the pathological damage in the CA1 area of the hippocampus was alleviated(P<0.05);compared with Model group and agomir NC group,neurological symptom score,mean arterial pressure,platelet adhesion rate and miR-296-5p expression of rats in the miR-296-5p agomir group were increased,survival time was shortened,and pathological damage in hippocampal CA1 region was aggravated(P<0.05).compared with the A Ⅲ-H group and the AⅢ-H+agomir NC group,the neurological symptom score,average arterial pressure,platelet adhesion rate and miR-296-5p expression of rats were in-creased,the survival time was shortened,and the pathological damage in hippocampal CA1 region was serious in the AⅢ-H+miR-296-5p agomir group(P<0.05).Conclusion A Ⅲ may treat SHR stroke by inhibiting the expression of miR-296-5p.
3.Effect of atractylenolide Ⅲ on stroke in spontaneously hypertensive rats and its mechanism
Jibo LI ; Yongwen FENG ; Wenfeng WU ; Xuezheng FAN ; Haixia LI
Journal of Clinical Medicine in Practice 2023;27(22):71-76
Objective To investigate the effect of atractylenolide Ⅲ(A Ⅲ)on stroke in spon-taneously hypertensive rats by regulating microRNA-296-5p(miR-296-5p)expression.Methods The spontaneously hypertensive rats(SHR)were given 0.9%sodium chloride solution freely for 2 months,and then fed with 1%sodium chloride solution to establish the stroke model of SHR.The rat models were randomly grouped into Model group,A Ⅲ low-dose group(A Ⅲ-L group),A Ⅲ high-dose group(A Ⅲ-H group),positive drug nimodipine group(Nim group),miR-296-5p agonist group(miR-296-5p agomir group),agomir NC group,A Ⅲ-H+miR-296-5p agomir group,and A Ⅲ-H+agomir NC group,with 12 in each group.The changes in neurological symptom scores,av-erage arterial pressure,survival time,and platelet adhesion rate were detected and recorded;hema-toxylin and eosin(HE)staining was applied to detect pathological changes in the CA1 region of the rat hippocampus;quantitative reverse transcription polymerase chain reaction(qRT-PCR)was ap-plied to detect the expression of miR-296-5p in the hippocampal CA1 region.Results Compared with the NC group,the Model group showed increases in neurological symptom score,mean arterial pressure,platelet adhesion rate,miR-296-5p expression,shortened survival time,and severe pathological damage to the hippocampal CA1 area(P<0.05);compared with the Model group,the neurological symptom scores,mean arterial pressure,platelet adhesion rate,and miR-296-5p expression in the A Ⅲ-L,A Ⅲ-H,and Nim groups decreased,the survival time was prolonged,and the pathological damage in the CA1 area of the hippocampus was alleviated(P<0.05);compared with Model group and agomir NC group,neurological symptom score,mean arterial pressure,platelet adhesion rate and miR-296-5p expression of rats in the miR-296-5p agomir group were increased,survival time was shortened,and pathological damage in hippocampal CA1 region was aggravated(P<0.05).compared with the A Ⅲ-H group and the AⅢ-H+agomir NC group,the neurological symptom score,average arterial pressure,platelet adhesion rate and miR-296-5p expression of rats were in-creased,the survival time was shortened,and the pathological damage in hippocampal CA1 region was serious in the AⅢ-H+miR-296-5p agomir group(P<0.05).Conclusion A Ⅲ may treat SHR stroke by inhibiting the expression of miR-296-5p.
4.Clinical efficacy and prognostic influencing factors of radical surgery for duodenal gastro-intestinal stromal tumor: a multicenter retrospective study
Jianzhi CUI ; Xin WU ; Peng ZHANG ; Linxi YANG ; Ye ZHOU ; Yuan YIN ; Xingyu FENG ; Zaisheng YE ; Yongjian ZHOU ; Youwei KOU ; Heli LIU ; Yuping ZHU ; Yan ZHAO ; Yongwen LI ; Haibo QIU ; Hao XU ; Zhijian YE ; Guoli GU ; Ming WANG ; Hui CAO
Chinese Journal of Digestive Surgery 2022;21(8):1056-1070
Objective:To investigate the clinical efficacy and prognostic influencing factors of radical surgery for duodenal gastrointestinal stromal tumor (GIST).Methods:The retrospective cohort study was conducted. The clinicopathological data of 741 duodenal GIST patients who under-went radical surgery in 17 medical centers, including 121 cases in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 121 cases in Chinese PLA General Hospital, 116 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 77 cases in Fudan University Shanghai Cancer Center, 77 cases in West China Hospital, Sichuan University, 31 cases in Guangdong Provincial People′s Hospital, 24 cases in Fujian Cancer Hospital, 22 cases in Fujian Medical University Union Hospital, 25 cases in Shengjing Hospital of China Medical University, 19 cases in Xiangya Hospital, Central South University, 23 cases in Zhejiang Cancer Hospital, 17 cases in Liaoning Cancer Hospital&Institute, 17 cases in the First Affiliated Hospital of Xiamen University, 15 cases in Sun Yat-sen University Cancer Center, 14 cases in the First Affiliated Hospital of Nanjing Medical University, 14 cases in Zhongshan Hospital Affiliated to Xiamen University and 8 cases in General Hospital of Chinese People′s Liberation Army Air Force, from January 2010 to April 2020 were collected. There were 346 males and 395 females, aged 55(range, 17?86)years. Observation indicators: (1) neoadjuvant treatment; (2) surgical and postoperative situations; (3) follow-up; (4) stratified analysis. Follow-up was conducted using outpatient examination or telephone interview. Patients were followed up once every 3?6 months during neoadjuvant therapy and once every 6?12 months after radical surgery to detect tumor recurrence and survival of patient up to April 2022. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-rank test was used for survival analysis. The COX regression model was used for univariate and multivariate analyses. Propensity score matching was done by the 1∶1 nearest neighbor matching method, and the matching tolerance was 0.02. Results:(1) Neoadjuvant therapy. Of the 741 patients, 34 cases received neoadjuvant therapy for 8(range, 3?44)months. Cases assessed as partial response, stable disease and progressive disease before the radical surgery of the 34 cases were 21, 9, 4, respectively. The tumor diameter of the 34 patients before the neoadjuvant therapy and before the radical surgery were 8.0(range, 3.0?26.0)cm and 5.3(range, 3.0?18.0)cm, with the regression rate as 31.9%(range, ?166.7% to 58.3%). (2) Surgical and postoperative situations. Of the 741 patients, 34 cases underwent radical surgery after receiving neoadjuvant therapy, and 707 cases underwent radical surgery directly. All the 741 patients underwent radical surgery successfully, in which 633, 102 and 6 cases received open surgery, laparoscopic surgery and endoscopic treatment, respectively. Of the 633 cases receiving open surgery and the 102 cases receiving laparoscopic surgery, cases with surgical resection range as pancreatoduodenectomy (PD) was 238, and cases with surgical resection range as duodenal limited resection, including duodenal wedge resection, distal gastrectomy, segmental duodenal resection, local resection of duodenal tumor or segmental duodenum combined with subtotal gastrectomy, was 497, 226, 55, 204, 12. Of the 741 patients, 131 cases had post-operative complications including 113 cases with grade Ⅰ?Ⅱ complications and 18 cases with ≥ grade Ⅲ complications of the Clavien-Dindo classification. The duration of postoperative hospital stay of the 741 patients was 13(range, 4?120)days. Of the 707 patients receiving direct radical surgery, 371 cases were evaluated as extremely low risk, low risk, medium risk of the modified National Institutes of Health (NIH) risk classification after surgery, and 336 cases were evaluated as high risk in which 205 cases receive postoperative adjuvant imatinib therapy with the treatment time as 24(range, 6?110)months. (3) Follow-up. All the 741 patients were followed up for 58(range, 7?150)months. During the follow-up, 110 patients had tumor recurrence and metastasis. The 1-, 3-, 5-year overall survival rates and 1-, 3-, 5-year disease-free survival rates of the 741 patients were 100.0%, 98.6%, 94.5% and 98.4%, 90.9%, 84.9%, respectively. The 1-, 3-, 5-year overall survival rates and 1-, 3-, 5-year disease-free survival rates of the 707 patients receiving direct radical surgery were 100.0%, 98.5%, 94.3% and 98.4%, 91.1%, 85.4%, respectively. (4) Stratified analysis. ① Analysis of prognostic factors in patients undergoing radical surgery directly. Results of univariate analysis showed that primary tumor location, tumor diameter, mitotic count, modified NIH risk classification and tumor gene information were related factors affecting the overall survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=0.43, 0.18, 0.22, 0.06, 0.29, 95% confidence intervals as 0.20?0.93, 0.09?0.35, 0.10?0.50, 0.03?0.12, 0.09?0.95, P<0.05). The primary tumor location, tumor diameter, mitotic count, modified NIH risk classification were related factors affecting the disease-free survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=0.65, 0.25, 0.25, 0.10, 95% confidence intervals as 0.41?1.03, 0.17?0.37, 0.15?0.42, 0.07?0.15, P<0.05). Results of multivariate analysis showed that primary tumor located at the horizontal segment of duodenum, mitotic count >5/50 high power field, tumor gene KIT exon 9 mutation were independent risk factors affecting the overall survival of 365 patients with primary duodenal GIST after removing 342 patients without tumor gene information who underwent direct radical surgery ( hazard ratio=2.85, 2.73, 3.13, 95% confidence intervals as 1.12?7.20, 1.07?6.94, 1.23?7.93, P<0.05). Tumor diameter >5 cm and mitotic count >5/50 high power field were independent risk factors affecting the disease-free survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=3.19, 2.98, 95% confidence intervals as 2.05?4.97, 1.99?4.45, P<0.05). ② Effect of postoperative adjuvant therapy on prognosis of high-risk patients of modified NIH risk classification. Of the 336 patients evaluated as high risk of the modified NIH risk classification, the 5-year overall survival rate and 5-year disease-free survival rate were 94.6% and 77.3% in the 205 cases with postoperative adjuvant therapy, versus 83.2% and 64.4% in the 131 cases without postoperative adjuvant therapy, showing significant differences between them ( χ2=8.39, 4.44, P<0.05). Of the 205 patients evaluated as high risk of the modified NIH risk classification who received postoperative adjuvant therapy, there were 106 cases receiving postoperative adjuvant therapy <36 months, with the 5-year overall survival rate and 5-year disease-free survival rate were 87.1% and 58.7%, and there were 99 cases receiving post-operative adjuvant therapy ≥36 months, with the 5-year overall survival rate and 5-year disease-free survival rate were 100.0% and 91.5%. There were significant differences in the 5-year overall survival rate and 5-year disease-free survival rate between the 106 patients and the 99 patients ( χ2=13.92, 29.61, P<0.05). ③ Comparison of clinical efficacy of patients with different surgical methods. Before propensity score matching, cases with primary tumor located at bulb, descending, horizontal, ascending segment of duodenum, cases with tumor diameter ≤5 cm and >5 cm were 95, 307, 147, 34, 331, 252, in the 583 patients receiving open surgery with complete clinical data, versus 15, 46, 17, 5, 67, 16 in the 83 patients receiving laparoscopic surgery with complete clinical data, showing no significant difference in the primary tumor location ( χ2=0.94, P>0.05), and a significant difference in the tumor diameter ( χ2=17.33, P<0.05) between them. After propensity score matching, the above indicator were 16, 39, 20, 8, 67, 16 in the 83 patients receiving open surgery, versus 15, 46, 17, 5, 67, 16 in the 83 patients receiving laparoscopic surgery, showing no significant difference between them ( χ2=1.54, 0.00, P>0.05). Cases with postoperative complications, cases with grade Ⅰ?Ⅱ complica-tions and ≥grade Ⅲ complications of the Clavien-Dindo classification, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate were 17, 12, 5, 11(range, 5?120)days, 92.0%, 100.0% in the 83 patients receiving open surgery, versus 9, 7, 2, 11(range, 5?41)days, 91.6%, 97.3% in the 83 patients receiving laparoscopic surgery, showing no signi-ficant difference in postoperative complications, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate ( χ2=2.91, Z=3 365.50, χ2=3.02, 1.49, P>0.05) between them. There was no significant difference in complications of the Clavien-Dindo classification between them ( P>0.05). ④ Comparison of clinical efficacy of patients with primary tumor located at the descending segment of duodenum who underwent surgery with different surgical resection scopes. Before propensity score matching, cases with tumor diameter ≤5 cm and >5 cm, cases with tumor located at opposite side of mesangium and mesangium were 71, 85, 28, 128 in the 156 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 92, 41, 120, 13 in the 133 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing significant differences between them ( χ2=16.34, 150.10, P<0.05). After propensity score matching, the above indicator were 28, 13, 16, 25 in the 41 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 28, 13, 16, 25 in the 41 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing no significant difference between them ( χ2=0.00, 0.00, P>0.05). Cases with postopera-tive complications, cases with grade Ⅰ?Ⅱ complications and ≥grade Ⅲ compli-cations of the Clavien-Dindo classification, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate were 13, 11, 2, 15(range, 9?62)days, 94.2%, 64.3% in the 41 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 9, 8, 0, 15(range, 7?40)days, 100.0%, 78.8% in the 41 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing no significant difference in post-operative complica-tions, the 5-year overall survival rate and 5-year disease-free survival rate ( χ2=0.99, 0.34, 1.86, P>0.05) between them. There was no significant difference in complications of the Clavien-Dindo classification ( P>0.05) and there was a significant difference in duration of postopera-tive hospital stay ( Z=614.50, P<0.05) between them. Conclusions:The clinical efficacy of radical surgery for duodenal GIST are ideal. Primary tumor located at the horizontal segment of duodenum, mitotic count >5/50 high power field, tumor gene KIT exon 9 mutation are independent risk factors affec-ting the overall survival of patients undergoing direct radical surgery and tumor diameter >5 cm and mitotic count >5/50 high power field are independent risk factors affecting the disease-free survival of patients. There is no significant difference in the short-term efficacy and long-term prognosis between patients undergoing open surgery and laparoscopic surgery. For patients with primary tumor located at the descending segment of duodenum, the duration of postoperative hospital stay is longer in patients undergoing PD compared with patients undergoing duodenal limited resection. For patients evaluated as high risk of the modified NIH risk classification, posto-perative adjuvant therapy and treatment time ≥36 months are conducive to improving the prognosis of patients.
5.Comparison of the performance of two methods to determine set-up errors for DIBH patients with left sided breast cancer in radiotherapy
Tantan LI ; Jianghu ZHANG ; Yongwen SONG ; Yu TANG ; Shunan QI ; Fengyu LU ; Wei ZHANG ; Zengzhou WANG ; Xin FENG ; Shirui QIN ; Bin CHENG ; Bofei LIU ; Guishan FU ; Shulian WANG ; Jianrong DAI
Chinese Journal of Radiation Oncology 2020;29(4):278-282
Objective:To establish the basic procedures of the application of optical surface monitoring system (OSMS) in the deep inspiration breath hold (DIBH) radiotherapy for patients with left sided breast cancer and compare the performance of OSMS and cone-beam CT (CBCT) in the determination of the set-up errors of DIBH radiotherapy for patients with left sided breast cancer.Methods:Twenty patients with left sided breast cancer received DIBH radiotherapy. Through the registration of CBCT images with the planning CT images, and the registration of OSMS radiography images with the outer contour of the body surface, translational set-up errors and rotational errors were determined along the lateral-medial ( Rx), superior-inferior ( Ry) and anterior-posterior ( Rz) directions. Pearson correlation analysis was performed to evaluate the correlation of the set-up errors determined by two methods, and Bland- Altman plot analysis was used to assess the coincidence of these two methods. Results:Two methods were positively correlated. The Rz volume was 0.84, 0.74 and 0.84 in the x, y and z directions, and 0.65, 0.41 and 0.54 in the Rx, Ry and Rz directions, respectively (all P<0.01). The 95% CI of agreement were within preset 5 mm tolerance (-0.37-0.42cm, -0.39-0.41cm, -0.29-0.49cm ) in x, y and z directions for two methods. The 95% CI of agreement were within preset 3 ° tolerance -2.9°-1.4°, -2.6°-1.4°, -2.4°-2.5°in Rx, Ry and Rz directions for two methods. The system errors of 20 patients with left sided breast cancer receiving DIBH radiotherapy were <0.18cm and the random errors were <0.24cm. Conclusions:OSMS is equivalent to CBCT in the determination and stimulation of set-up errors for patients with left sided breast cancer receiving DIBH radiotherapy. The combination of CBCT and OSMS is a safe and reliable method.
6.Prediction of deep learning-based radiomic features for neoadjuvant radiochemotherapy response in locally advanced rectal cancer
Ning LI ; Qi SHARON ; Lingling FENG ; Yuan TANG ; Yexiong LI ; Ye REN ; Hui FANG ; Yu TANG ; Bo CHEN ; Ningning LU ; Hao JING ; Shunan QI ; Shulian WANG ; Yueping LIU ; Yongwen SONG ; Jing JIN
Chinese Journal of Radiation Oncology 2020;29(6):441-445
Objective:To evaluate the effectiveness of deep learning (DL)-based radiomic features extracted from pre-treatment diffusion-weighted magnetic resonance images (DWI) for predicting neoadjuvant chemoradiation treatment (nCRT) response in patients with locally advanced rectal cancer (LARC).Methods:Forty-three patients receiving nCRT from 2016 to 2017 were included. All patients received DWI before nCRT and total mesorectal excision surgery 6-12 weeks after completion of nCRT. The patient-cohort was split into the responder group ( n=22) and the non-responder group ( n=21) based on the post-nCRT response assessed by postoperative pathology, MRI or colonoscopy. DL-based radiomic features were extracted from the apparent diffusion coefficient map of the DWI using a pre-trained convolution neural network, respectively. Least absolute shrinkage and selection operator-Logistic regression models were constructed using extracted radiomic features for predicting treatment response. The model performance was evaluated with repeated 20 times stratified 4-fold cross-validation using receiver operating characteristic (ROC) curves. Results:The model established with DL-based radiomic features achieved the mean area under the ROC curve of 0.73(SE, 0.58-0.80).Conclusion:DL-based radiomic features extracted from pre-treatment DWI achieve high accuracy for predicting nCRT response in patients with LARC.
7.Associations of Genetic Variations in Mismatch Repair Genes MSH3 and PMS1 with Acute Adverse Events and Survival in Patients with Rectal Cancer Receiving Postoperative Chemoradiotherapy
Jie YANG ; Ying HUANG ; Yanru FENG ; Hongmin LI ; Ting FENG ; Jinna CHEN ; Luxi YIN ; Weihu WANG ; Shulian WANG ; Yueping LIU ; Yongwen SONG ; Yexiong LI ; Jing JIN ; Wen TAN ; Dongxin LIN
Cancer Research and Treatment 2019;51(3):1198-1206
PURPOSE: Mismatch repair (MMR) deficiency plays a critical role in rectal cancer. This study aimed to explore the associations between genetic variations in seven MMR genes and adverse events (AEs) and survival of patients with rectal cancer treated with postoperative chemoradiotherapy (CRT). MATERIALS AND METHODS: Fifty single nucleotide polymorphisms in seven MMR (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) genes were genotyped by Sequenom MassARRAY method in 365 patients with locally advanced rectal cancer receiving postoperative CRT. The associations between genotypes and AEs were measured by odds ratios and 95% confidence intervals (CIs) by unconditional logistic regression model. The associations between genetic variations and survival were computed by the hazard ratios and 95% CIs by Cox proportional regression model. RESULTS: The most common grade ≥ 2 AEs in those 365 patients, in decreasing order, were diarrhea (44.1%), leukopenia (29.6%), and dermatitis (18.9%). Except 38 cases missing, 61 patients (18.7%) died during the follow-up period. We found MSH3 rs12513549, rs33013 and rs6151627 significantly associated with the risk of grade ≥ 2 diarrhea. PMS1 rs1233255 had an impact on the occurrence of grade ≥2 dermatitis. Meanwhile, PMS1 rs4920657, rs5743030, and rs5743100 were associated with overall survival (OS) time of rectal cancer. CONCLUSION: These results suggest that MSH3 and PMS1 polymorphisms may play important roles in AEs prediction and prognosis of rectal cancer patients receiving postoperative CRT, which can be potential genetic biomarkers for rectal cancer personalized treatment.
Biomarkers
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Chemoradiotherapy
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Dermatitis
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Diarrhea
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DNA Mismatch Repair
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Follow-Up Studies
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Genetic Variation
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Genotype
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Humans
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Leukopenia
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Logistic Models
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Methods
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Odds Ratio
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Polymorphism, Single Nucleotide
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Prognosis
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Rectal Neoplasms
8.Radical surgery combined with adjuvant radiotherapy for elderly patients aged over 75 years with stage II( or III( rectal cancer: a retrospective study from a single center.
Wenyang LIU ; Jing JIN ; Yexiong LI ; Shulian WANG ; Yongwen SONG ; Yueping LIU ; Weihu WANG ; Hua REN ; Hui FANG ; Ning LI ; Yuan TANG ; Xin WANG ; Yu TANG ; Ningning LU ; Qin XIAO ; Yanru FENG ; Jianyang WANG ; Lei DENG ; Hao JING ; Xinfan LIU ; Zihao YU
Chinese Journal of Gastrointestinal Surgery 2018;21(6):654-659
OBJECTIVETo evaluate the outcome of radical surgery combined with adjuvant radiotherapy for patients aged over 75 years with stage II( or III( rectal cancer.
METHODSFrom 2000 to 2010, 178 patients aged over 75 years at diagnosis who underwent radical surgery in National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, were selected from 3995 patients with stage II( or III( rectal cancer in the database of the above center and enrolled into this retrospective cohort study, which was approved by ethics committee of the above hospital (ClinicalTrials.gov number, NCT02312284).
RESULTSMedian age of patients was 77 years (range 75-87). There were 37 (20.8%), 69 (38.8%), and 72 (40.4%) patients with tumors locating in the high, middle and low rectum respectively; 89(50%) patients of pathological stages II( and III( respectively; 21(11.8%), 137(77%), 19(10.7%), and 1(0.6%) patients with poorly, moderately, well differentiated adenocarcinoma, and mucinous adenocarcinoma respectively. The Charlson/Deyo comorbidity index (CCI) score was 0 in the majority (73.6%) of patients. Fifty-three patients underwent abdominoperineal resection, 116 underwent low anterior resection and 9 underwent Hartmann resection. All the patients received computed tomography-based simulation and treatment planning using an anal marker in a prone or supine position. Patients were treated with linear accelerator by megavoltage photons (6MV), with 2D technique in early years and 3D conformal or simplified intensity-modulated radiotherapy technique later, at a dose of 50 Gy in 25 fractions to the pelvis within an overall treatment time of 35 days. Sixty-one patients (34.3%) received surgery combined with radiation (ART group), in whom 16 received radiation alone 117 patients did not receive radiation(NORT group). The baseline data between ART and NORT group were not significantly different(all P>0.05). There was no significant difference in 5-year overall survival between ART and NORT groups (61.0% vs. 63.0%, P=0.586). The cumulative local relapse was 10.9% and 25.4% in ART and NORT group respectively (P=0.032). Cox multivariate analysis revealed that surgery combined with radiation improved local control significantly(HR=0.27, 95%CI:0.11-0.68, P=0.005).
CONCLUSIONSFor elderly patients aged over 75 years with stage II( or III( rectal cancer, radical surgery combined with radiation does not increase the overall survival, but can improve local control rate. It is reasonable to selectively apply adjuvant radiotherapy to the elderly patients in the setting of radical surgery.
Adenocarcinoma ; radiotherapy ; surgery ; Aged ; Aged, 80 and over ; Humans ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Radiotherapy, Adjuvant ; Rectal Neoplasms ; radiotherapy ; surgery ; Retrospective Studies
9.Neoadjuvant rectal score in prognostic prediction of clinical stage Ⅲ middle-low rectal cancer
Shuai LI ; Jing JIN ; Feng YE ; Yuan TANG ; Ning LI ; Jing YU ; Hua REN ; Xin WANG ; Yang Wen LIU ; Shulian WANG ; Yongwen SONG ; Weihu WANG ; Yueping LIU ; Hui FANG ; Ning Ning LU ; Yu TANG ; Shunan QI ; Bo CHEN ; Yexiong LI
Chinese Journal of Radiation Oncology 2018;27(5):467-472
Objective To investigate the effects of downstaging and neoadjuvant reetal(NAR) score on the prognosis of patients with clinical stage Ⅲ middle-low rectal cancer undergoing preoperative concurrent chemoradiotherapy.Methods From 2006 to 2014,195 patients who were admitted to our hospital and diagnosed with clinical stage Ⅲ middle-low rectal cancer by pelvic magnetic resonance imaging or computed tomography were enrolled.All patients received preoperative radiotherapy with doses of 42-50.4 Gy (median:50 Gy,93.8% of patients received doses of ≥ 50 Gy) and concurrent chemotherapy with capecitabine ± oxaliplatin.Total mesorectal (R0) excision surgery was performed at 4-15 weeks (median:7 weeks) after concurrent chemoradiotherapy.The effects of downstaging (stage yp0-Ⅱ) and NAR score (calculated based on cT staging and ypT/N staging) on the prognosis were evaluated.The 3-year disease-free survival (DFS) rate was calculated using the Kaplan-Meier method and analyzed by log-rank test.Results In all the patients,the median follow-up time was 44 months (6.7-125.5 months);the 3-year DFS rate was 76.8%.Downstaging after preoperative chemoradiotherapy was a significant prognostic factor for the 3-year DFS (92.2% vs.56.8%,P=0.000).The median NAR score was 15.0(0-65.0) in all the patients.Patients with NAR scores of ≤ 15.0 had significantly improved 3-year DFS than those with NAR scores of>15.0(90.1% vs.57.0%,P=0.001).In patients with downstaging,those with NAR scores of ≤8.4 had significantly improved prognosis compared with those with NAR scores of> 8.4(95.1% vs.87.5%,P=0.022).Conclusions Patients with downstaging after preoperative concurrent chemoradiotherapy for stage c Ⅲ middle-low rectal cancer have satisfactory prognosis.The NAR score is an effective prognostic predictor.
10.Preliminary clinical application of transcatheter closure of ventricular septal defect via radial approach
Wendong TANG ; Xudong XU ; Yuan BAI ; Jian SHEN ; Feng CHEN ; Ni ZHU ; Yongwen QIN ; Xianxian ZHAO
Journal of Interventional Radiology 2018;27(2):114-117
Objective To explore the feasibility and efficacy of transcatheter closure of ventricular septal defect (VSD) through radial artery combined femoral vein approach. Methods A total of 11 patients with congenital VSD, who were admitted to authors' hospital during the period from June 2017 to November2017, were enrolled in this study. The patterns of lesion included intracristal type (n=3) and perimembranous type (n=8), and in 3 patients the VSD was associated with concant ventricular septal aneurysm. Transcatheter closure of VSD via radial approach was carried out in all patients. The mean age of the patients was (37.82±12.44) years old, and the average body weight was (62.79±14.95) kg. The transthoracic echocardiography (TTE) showed that the mean diameter of VSD was (5.87±1.91)mm. The effect of transcatheter closure therapy was assessed by intraoperative TTE and left ventriculography. All patients were followed up with electrocardiogram and TTE at 24 hours and one, 3, 6 months after transcatheter closure therapy. Results Successful closure was achieved in 10 patients, and one patient had to be transferred to surgery because the catheter could not pass through the defect. The mean diameter of the implanted occluders was (7.50±3.60)mm, the average procedural time and fluoroscopy time were (47.20±5.45) min and (13.00±3.65) min respectively. The postoperative average in-bed time was (99.00±11.97) min. Two patients developed radial artery spasm during the operation. During the follow-up period lasting for a mean of (3.50±1.90) months, no serious complications, such as dropping of occluder, residual shunt, atrioventricular block, aortic regurgitation, radial artery occlusion, etc. occurred in the 10 patients. Conclusion For the treatment of VSD, transcatheter closure through radial artery combined with femoral vein approach is safe and effective. Therefore, this technique is worthy of clinical application.

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