1.Analysis of red blood cell transfusion reactions in China from 2018 to 2023
Bo PAN ; Xiaoyu GUAN ; Jue WANG ; Yunlong PAN ; Liu HE ; Haixia XU ; Xin JI ; Li TIAN ; Ling LI ; Zhong LIU
Chinese Journal of Blood Transfusion 2025;38(5):704-710
Objective: To analyze the demographic characteristics of patients with red blood cell transfusion reactions, the usage of red blood cell preparations, and the differences in the composition ratio of adverse reactions based on multi-center data from the Haemovigilance Network, in order to reveal the clinical characteristics of red blood cell transfusion and its underlying issues. Methods: Clinical data of patients who experienced transfusion reactions after red blood cell transfusion in the Haemovigilance Network from 2018 to 2023 were collected. The demographic characteristics of patients who experienced transfusion reactions with different types of red blood cell preparations, the utilization of these preparations, and the differences of the composition ratios of transfusion reactions were analyzed. Count data were expressed as numbers (n) or percentages (%), and comparisons between groups were performed using the Chi-square test. Results: Red blood cell transfusion reactions were more common in females (53.56%), with the majority of patients aged 50-69 years (35.54%). The Han polulation accounted for the vast majority of patients (92.77%), and patients in the hematology and obstetrics/gynecology departments had a relatively high proportion of transfusion reactions (13.26% and 14.26%, respectively). Leukocyte-reduced red blood cells and suspended red blood cells were the most common types of transfusion reactions reported among red blood cell preparations. Allergic reactions and non-hemolytic febrile reactions were the most common transfusion reactions, and there were significant differences in the composition ratios of allergic reactions (χ
=869.89, P<0.05) and non-hemolytic febrile reactions (χ
=812.75, P<0.05) across various types of red blood cell preparations. Conclusion: There are differences in the demographic characteristics and composition ratio of transfusion reactions among different red blood cell preparations. The management of red blood cell transfusion reactions should be tailored to patient characteristics and conditions, and the selection and use of blood products should be optimized to reduce or avoid the occurrence of transfusion reactions, such as considering the use of washed red blood cells for patients with a history of transfusion allergies or those prone to allergies.
2.Strategy to Guide Revascularization of Non-culprit Lesions in Patients With STEMI:State of Art and Future Prospects
Yingyang GENG ; Yin ZHANG ; Chujie ZHANG ; Han ZHANG ; Jingjing XU ; Ying SONG ; Cheng CUI ; Pei ZHU ; Lijian GAO ; Zhan GAO ; Jue CHEN ; Lei SONG
Chinese Circulation Journal 2024;39(3):301-305
Acute ST-segment elevation myocardial infarction with multivessel disease is one of the high-risk types of coronary heart disease.Early opening of infarct-related artery and reperfusion of myocardium could significantly reduce the mortality in acute phase.However,the presence of non-culprit lesions in non-infarct-related arteries is still at risk and has an important impact on the long-term prognosis of patients.It remains controversial on how to precisely evaluate the clinical significance and revascularization value of non-culprit lesions.This article aims to review the research status and progress of guidance strategies of non-culprit lesion revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease.
3. Effects of the proliferation, migration and apoptosis of AHVAC - on gastric cancer MKN-28 cells
Xiaomei HUANG ; Hui ZHI ; Hao CHEN ; Linming LU ; Xiaoqun ZHU ; Lizhen WANG ; Jue ZHOU ; Jinjin PANG ; Jinliang XU
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(3):270-276
AIM: To investigate the effects of agkis-trodon halys venom anti-tumor component (AHVAC-) on the biological behavior of gastric cancer MKN-28 cells. METHODS: Gastric cancer MKN-28 cells were treated with the experimental concentrations (5, 10, 15 μg/mL) of AHAVC- for 24 h. Cell proliferation and toxicity assay (cell counting kit-8, CCK-8) was used to detect the inhibition rates of the cells in different concentrations of AHVAC-. The migration ability of the cells was evaluated by wound-healing and Transwell assay. The apoptosis were observed by laser confocal microscopy with annexin V-mCherry/DAPI double staining, and the apoptosis rates were analyzed by flow cytometry with annexin V-FITC/PI double fluorescence staining. The protein level of Caspease-3 was determined by Western blot. RESULTS: Compared with normal control group, the results of AHVAC- concentration groups showed that with the increase of AHVAC- concentration, the proliferative activity of MN-28 cells decreased gradually (P<0.01), the cell migration ability decreased gradually (P<0.01), and the cell apoptosis rate increased (P<0.05). The expression of apoptosis-related protein Caspease-3 was up-regulated (P<0.01). CONCLUSION: AHVAC- inhibits proliferation and migration of gastric cancer MSN-28 cells and induces apoptosis.
4.Mechanism of action of cinobufotalin in inhibiting lung metastasis of hepatocellular carcinoma by regulating AKT-mediated epithelial-mesenchymal transition in a nude mouse model
Yue YANG ; Siyu XU ; Jue WANG ; Shilin DU ; Chunlei ZHANG ; Haiyan SONG
Journal of Clinical Hepatology 2024;40(9):1840-1847
Objective To investigate the effect and mechanism of cinobufotalin in inhibiting hepatocellular carcinoma(HCC)metastasis by regulating epithelial-mesenchymal transition(EMT).Methods A total of 36 male BALB/c nude mice,aged 6 weeks,were given injection of MHCC97H cells via the caudal vein to establish a model of HCC lung metastasis,and then the mice were randomly divided into high-and low-dose cinobufotalin groups and control group.Since the day of modeling,the mice in the high-and low-dose cinobufotalin groups were given intraperitoneal injection of cinobufotalin at a dose of 120 μL/kg and 60 μL/kg,respectively,and those in the control group were given intraperitoneal injection of normal saline,twice a week.After 8 weeks,HE staining was performed for lung tissue to measure the lung metastasis rate of HCC.MHCC97H cells were treated with high-dose(2.5 μL/mL)or low-dose(5 μL/mL)cinobufotalin for 24 hours,and wound healing assay,RT-PCR,and Western blot were used to measure cell migration ability and the expression of EMT-related molecules.MHCC97H cells were induced in a simulated hypoxic environment with CoCl2 incubation,with high-and low-dose cinobufotalin added for intervention,and wound healing assay and Western blot were used to investigate the effect of cinobufotalin on cell migration ability and EMT induced by hypoxia.Transcriptome analysis was used to investigate the effect mechanism of cinobufotalin on MHCC97H cells,and Western blot was used to observe the effect of cinobufotalin on the expression levels of protein kinase B(AKT)and phosphorylated AKT(P-AKT)in MHCC97H cells.A one-way analysis of variance was used for comparison of continuous data between multiple groups,and the least significant difference t-test was used for further comparison between two groups;the independent-samples t test was used for comparison of categorical data between two groups.Results Compared with the control group,the cinobufotalin group had a significant reduction in the lung metastasis rate of HCC.Compared with the control group,cinobufotalin intervention reduced the wound healing rate of MHCC97H cells,upregulated the expression of epithelial-type molecules(t=2.860,P<0.05),and downregulated the expression of EMT transcription factors(EMT-TFs)and mesenchymal molecules(t=3.545,2.022,2.852,and 2.341,all P<0.05).Hypoxia induction upregulated the wound healing rate of MHCC97H cells and the expression levels of mesenchymal molecules and EMT-TFs(P<0.05),and cinobufotalin intervention reversed EMT change and inhibited wound healing(P<0.05).The transcriptome analysis of MHCC97H cells showed significant gene differences between the cinobufotalin group and the control group,and cinobufotalin mainly affected the expression of genes associated with tumor,metabolism,immunity,and signal transduction,with the largest number of differentially expressed genes in the AKT signal transduction pathway.Further measurement showed that cinobufotalin intervention downregulated the expression levels of AKT,P-AKT,and P-AKT/AKT in MHCC97H cells(t=2.434,3.401,and 2.258,all P<0.05).Conclusion Cinobufotalin can inhibit the metastasis of HCC,especially hypoxia-induced HCC metastasis,and regulation of EMT mediated by the AKT signal transduction pathway in HCC cells might be one of its mechanisms of action.
5.Heterogeneity of Wnt1-Cre-marked and Pax2-Cre-marked first branchial arch cranial neural crest cells in mice
Jue XU ; Shuang LIU ; Honggao FU ; Meiying SHAO ; Meiling CHEN ; Zhen HUANG
West China Journal of Stomatology 2024;42(4):435-443
Objective This study aimed to explore the heterogeneity and gene ontology of Wnt1-Cre-marked and Pax2-Cre-marked first branchial arch cranial neural crest cells(CNCs)in mice.Methods The embryos of Wnt1-Cre;R26RmTmG and Pax2-Cre;R26RmTmG at embryonic day(E)8.0-E9.25 were collected for histological observation.We per-formed immunostaining to compare green fluorescent pro-tein(GFP)-positive CNCs in Pax2-Cre;R26RAi9 and Wnt1-Cre;R26RAi9 mice at E15.5.Single-cell RNA sequencing(scRNA-seq)was used to analyze the first branchial arch GFP-positive CNCs from Wnt1-Cre;R26RmTmG and Pax2-cre;R26RmTmGmice at E10.5.Real time fluorescence quantitative polymerase chain reaction(q-PCR)was performed to val-idate the differential genes.Results Wnt1-Cre-marked and Pax2-Cre-marked CNCs migrated from the neural plateto first and second branchial arches and to the first branchial arch,respectively,at E8.0.Although Wnt1-Cre-marked and Pax2-Cre-marked CNCs were found mostly in cranial-facial tissues,the former had higher expression in palate and tongue.The results of scRNA-seq showed that Pax2-Cre-marked CNCs specifically contributed to osteoblast differentia-tion and ossification,while Wnt1-Cre-marked CNCs participated in limb development,cell migration,and ossification.The q-PCR data also confirmed the results of gene ontology analysis.Conclusion Pax2-Cre mice are perfect experimen-tal animal models for research on first branchial arch CNCs and derivatives in osteoblast differentiation and ossification.
6.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
7.Effect of proprotein convertase subtilisin/kexin type 9 inhibitor combined with rosuvastatin on lipid levels and short-term prognosis in patients with acute ischemic stroke
Xiaoya ZHOU ; Guofang CHEN ; Wenli ZHANG ; Hui NI ; Weiwei LIU ; Hui XU ; Chen WANG ; Yinsheng CHEN ; Jue WANG
Chinese Journal of Neurology 2024;57(6):625-633
Objective:To observe the effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor combined with rosuvastatin on lipid levels and short-term prognosis in patients with acute ischemic stroke, and to explore the optimal therapeutic regimen in terms of efficacy and safety, so as to provide a basis for clinical practice.Methods:Consecutive patients with acute cerebral infarction within 72 hours of onset and lipids≥2.6 mmol/L admitted to Xuzhou Central Hospital from April 2022 to March 2023 were included in the study, and the randomized numeric table method was used to divide them into 3 groups of different treatment regimens, group A (rosuvastatin 20 mg, once a day), group B (rosuvastatin 10 mg, once a day+alirocumab 75 mg, once 2 weeks) and group C (rosuvastatin 20 mg, once a day+alirocumab 75 mg, once 2 weeks). General baseline data, National Institutes of Health Stroke Scale score, modified Rankin Scale score on day 90 and the occurrence of adverse events and serious adverse events were collected from the 3 groups. The primary efficacy outcome was the degree of reduction in low density lipoprotein-cholesterol (LDL-C) from baseline on day 90. The secondary efficacy outcomes were recurrence rate and time to recurrence in stroke patients within 90 days,etc. The primary safety outcome was hepatic insufficiency (transaminase elevation≥3 times normal) within 90 days. The secondary safety outcomes were death due to stroke within 90 days and fatal and nonfatal myocardial infarction.Results:A total of 501 patients were included, 166 patients in group A, 167 patients in group B, and 168 patients in group C. The differences in the baseline data of the 3 groups were not statistically significant (all P>0.05). LDL-C was reduced from baseline on day 90 in groups A, B, and C, with the differences of -1.5 (-1.7, -1.4) mmol/L, -2.2 (-2.5, -2.1) mmol/L and -2.2 (-2.6, -2.1) mmol/L, respectively, with statistically significant differences among the 3 groups ( H=1.497, P<0.001); the differences between the group A and group B, and between the group A and group C, were statistically significant ( Z=-11.125, P=0.006; Z=-9.475, P=0.012), while the difference between the group B and group C was not statistically significant ( Z=1.650, P=0.946). The numbers of 90-day stroke recurrence cases (recurrence rate) in patients in the groups A, B, and C were 12 (7.2%), 4 (2.4%), and 5 (3.0%), respectively, without statistically significant difference among the 3 groups ( χ 2=5.773, P>0.05); the recurrence time of patients in the groups A, B and C was (43.0±7.4) d, (66.0±8.3) d and (62.2±5.6) d, respectively, and the differences among the 3 groups were statistically significant ( F=14.096, P=0.001). Compared with the group A, patients in the groups B and C had a prolonged time to stroke recurrence within 90 days ( Z=-3.108, P=0.002; Z=-2.871, P=0.004), whereas the difference in the time to stroke recurrence within 90 days between patients in the groups B and C was not statistically significant ( Z=0.397, P=0.692). The time to stroke recurrence within 90 days was positively correlated with the level of LDL-C on day 90 ( β=0.850, P=0.031). Ten patients (6.0%) in the group A developed hepatic insufficiency, 1 patient (0.6%) in the group B, and 9 patients (5.4%) in the group C. The differences among the 3 groups were statistically significant (χ 2=7.622, P=0.022); and the difference between the group B and group C was statistically significant ( P=0.011). The differences of secondary safety endpoints, death due to stroke within 90 days [1 case (0.6%) in the group A, 0 case (0) in the group B, and 1 case (0.6%) in the group C], fatal and nonfatal myocardial infarction within 90 days [3 cases (1.8%) in the group A, 1 case (0.6%) in the group B, and 1 case (0.6%) in the group C], were not statistically significant among the 3 groups (all P>0.05). Conclusions:In patients with acute ischemic stroke, PCSK9 inhibitor combined with rosuvastatin (both medium and high doses) significantly reduced LDL-C levels compared with baseline, and at the same time prolonged the time to stroke recurrence, reduced adverse effects such as hepatic insufficiency, and had a high degree of safety. PCSK9 inhibitor combined with medium-dose rosuvastatin had a better effect.
8.Effects of interactive Tuina on spatiotemporal gait parameters in children with spastic cerebral palsy
Xi FANG ; Chunxin XU ; Yunhui MI ; Kexing SUN ; Jue HONG
Journal of Acupuncture and Tuina Science 2024;22(4):289-296
Objective:To discuss the effects of walking function-guided interactive Tuina(Chinese therapeutic massage)on spatiotemporal gait parameters in children with spastic cerebral palsy(CP). Methods:Fifty children with spastic diplegic CP were divided into an observation group and a control group following a paired design and random number principle,with 25 cases in each group.The observation group was treated with the walking function-guided interactive Tuina,and the control group was offered the"six methods of spine and back"Tuina,20 min for each session and 5 sessions weekly for 3 consecutive months.The children's changes were assessed using the percentage of dimension E(walking,running,and jumping)of the gross motor function measure-88(GMFM-88)and three-dimensional gait analysis. Results:After treatment,the percentage of GMFM-88 dimension of dimension E(walking,running,and jumping)changed significantly in both groups(P<0.05),and the between-group difference was also statistically significant(P<0.05).After treatment,the step length,walking speed,and step frequency changed markedly in the observation group(P<0.05)and were significantly different from those in the control group(P<0.05).After the intervention,the stance phase and double support extended,and the swing phase became shorter in the observation group(P<0.05);the between-group differences were statistically significant(P<0.05).The maximal knee flexion angle and maximal posterior pelvic tilt angle decreased After treatment in the observation group,and the maximal anterior pelvic tilt angle increased,all showing statistical significance(P<0.05);the between-group differences were statistically significant(P<0.05). Conclusion:Compared with the passive Tuina manipulations,the"six methods of the spine and back",walking function-guided interactive Tuina has its advantage in improving walking function in children with spastic CP,manifesting as better lower-limb force line and walking efficiency.
9.Association between inflammation, body mass index, and long-term outcomes in patients after percutaneous coronary intervention: A large cohort study.
Guyu ZENG ; Deshan YUAN ; Sida JIA ; Peizhi WANG ; Liu RU ; Tianyu LI ; Ce ZHANG ; Xueyan ZHAO ; Song LEI ; Lijian GAO ; Jue CHEN ; Yuejin YANG ; Shubin QIAO ; Runlin GAO ; Xu BO ; Jinqing YUAN
Chinese Medical Journal 2023;136(14):1738-1740
10.Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total neoadjuvant therapy of locally advanced rectal cancer: the preliminary single-center findings of a prospective, multicentre, randomized phase II trial (TORCH).
Ya Qi WANG ; Li Jun SHEN ; Jue Feng WAN ; Hui ZHANG ; Yan WANG ; Xian WU ; Jing Wen WANG ; Ren Jie WANG ; Yi Qun SUN ; Tong TONG ; Dan HUANG ; Lei WANG ; Wei Qi SHENG ; Xun ZHANG ; Guo Xiang CAI ; Ye XU ; San Jun CAI ; Zhen ZHANG ; Fan XIA
Chinese Journal of Gastrointestinal Surgery 2023;26(5):448-458
Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Humans
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Middle Aged
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Chemoradiotherapy
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Immune Checkpoint Inhibitors/therapeutic use*
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Neoadjuvant Therapy
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Prospective Studies
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Rectal Neoplasms/pathology*
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Thrombocytopenia/drug therapy*
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Treatment Outcome
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Adult
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Aged

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