1.Clinical practice guidelines for intraoperative cell salvage in patients with malignant tumors
Changtai ZHU ; Ling LI ; Zhiqiang LI ; Xinjian WAN ; Shiyao CHEN ; Jian PAN ; Yi ZHANG ; Xiang REN ; Kun HAN ; Feng ZOU ; Aiqing WEN ; Ruiming RONG ; Rong XIA ; Baohua QIAN ; Xin MA
Chinese Journal of Blood Transfusion 2025;38(2):149-167
Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.
2.Study of action of multi-glycosides of Tripterygium wilfordii in regulating sphingosine kinases pathway to improve renal injury in IgA nephropathy rats
Zi-Lu MENG ; Chun-Dong SONG ; Yao-Xian WANG ; Xia ZHANG ; Ying DING ; Xian-Qing REN ; Wen-Sheng ZHAI
The Chinese Journal of Clinical Pharmacology 2024;40(6):879-883
Objective To study the mechanism of the amelioration of renal injury in immunoglobulin A nephropathy(IgAN)rats by multi-glycosides of Tripterygium wilfordii(GTW)based on the sphingosine kinase 1(Sphk1)/sphingosine 1-phosphate receptor 2(S1PR2)signalling pathway.Methods An IgAN rat model was established by means of bovine serum albumin gavage+castor oil and carbon tetrachloride subcutaneous injection+lipopolysaccharide tail vein injection.The rats were randomly divided into the model,control and experimental groups,with 9 rats in each group,and 10 normal rats were taken as the blank group.In the control group,6.25 mg·kg-1·d-1 prednisone was given by gavage;in the experimental group,9.375 mg·kg-1·d-1GTW was given by gavage;and in the blank and model groups,0.5 mL·100 g-1·d-1 0.9%NaCl was given by gavage,and the drugs were administered to the rats once a day in each group.At the end of the 15th week,urine samples were collected and blood albumin(ALB),blood urea nitrogen(BUN),24 hour-urine protein quantification(24 h-UTP),and urine erythrocyte counts were determined in each group,and the expression levels of Sphk1/S1PR2 proteins in each group were detected by Western blotting.Results The renal pathological changes in the control and experimental groups were significantly reduced compared with those in the model group by hematoxylin-eosin staining and immunofluorescence.The levels of ALB in the blank,model,control and experimental groups were(32.49±2.23),(22.98±0.51),(26.01±1.33)and(26.53±1.92)g·L-1;the levels of BUN were(6.11±1.71),(13.75±2.96),(6.71±1.35)and(4.77±0.99)mmol·L-1;the levels of 24 h-UTP were(5.72±1.96),(9.12±2.15),(5.78±2.05)and(4.75±1.50)mg·24 h-1;the urine erythrocyte counts were(9.73±2.40),(14.62±2.60),(9.90±1.59)and(9.46±2.94)cell·μL-1;the relative expression levels of Sphk1 protein were 0.85±0.02,1.47±0.02,1.06±0.02 and 1.09±0.02;the relative expression levels of S1PR2 protein were 0.27±0.02,0.88±0.01,0.43±0.02,and 0.42±0.02,respectively.The above indexes in the model group were statistically significant when compared with those of the control group and the experimental group(all P<0.01).Conclusion GTW may reduce the proliferation of mesangial cells by inhibiting the Sphk1/S1PR2 signalling pathway,thus attenuating kidney injury in IgAN rats.
3.Simultaneous content determination of twelve constituents in Bushen Huoxue Sanjie Capsules by HPLC
Ji-Yao YIN ; Jing HU ; Xia SHEN ; Xiao-Min CUI ; Hui REN ; Tong QU ; Ning LI ; Wen-Jin LU ; Zhi-Yong CHEN ; Kai QU
Chinese Traditional Patent Medicine 2024;46(1):1-6
AIM To establish an HPLC method for the simultaneous content determination of gallic acid,protocatechuic acid,morroniside,loganin,sweroside,paeoniflorin,hypericin,astragalin,salvianolic acid B,salvianolic acid A,epimedin C and icariin in Bushen Huoxue Sanjie Capsules.METHODS The analysis was performed on a 30℃thermostatic Agilent 5 TC-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 8),whose average recoveries were 97.11%-101.14%with the RSDs of 0.60%-2.65%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Bushen Huoxue Sanjie Capsules.
4.Discussion on the Pathogenesis and Treatment of Children Enuresis Based on the Theory "Kidney-Marrow-Brain" Axis and "Yin Heel Channel (阴跷脉)"
Bo ZHANG ; Xianqing REN ; Wen FU ; Yuying SUN ; Xiaoyu LIU ; Chundong SONG ; Xia ZHANG ; Qingyin GUO ; Ying DING
Journal of Traditional Chinese Medicine 2024;65(9):909-914
Guided by the theory of "kidney generates marrow", the study elaborates the viewpoint that the route of Yin Heel Channel (阴跷脉) is consistent with the "kidney-marrow-brain" axis from the perspective of the circulation of the meridians and the relationship between the zang-fu organs. Accordingly, it is believed that disease of Yin Heel Channel and dysfunction of the "kidney-marrow-brain" axis are the core pathogenesis of children enuresis, and it is elaborated from the following three major aspects, firstly, insufficient kidney essence, dysfunction of the "kidney-marrow-brain" axis, secondly, disease of Yin Heel Channel and deficiency and cold in lower jiao, and thirdly, disease of Yin Heel Channel and loss of nourishment of Chong Vessel. It is proposed to use the mode of "firstly needle, secondly moxibustion, and lastly consolidation" to treat children enuresis. Needle is to adjust yin and yang, warm yang and tonify kidney, and wake up the brain and open the orifices. The acupoints in Yin Heel Channel such as Zhaohai (KI 6), Jiaoxin (KI 8) and confluence points of the eight extraordinary vessels such as Waiguan (TE 5), Zulinqi (GB 41) are used, together with Baihui (GV 20), Yintang (EX-HN 3), Guanyuan (CV 4), Qixue (KI 13), Dazhong (KI 4). Moxibustion is to reinforce healthy qi and warm yang, bank up the root and consolidate the original qi by moxibustion at Shenque (CV 8), Mingmen (GV 4), and Xuanshu (GV 5). Consolidation is to use acupoints application to consolidate the therapeutic effect, and Guanyuan (CV 4) & Pangguangshu (BL 28), Qihai (CV 6) & Zhishi (BL 52), and Shenque (CV 8) & Ciliao (BL 32) are commonly used as the three groups of acupoints to warm the kidney and stop collapse, regulate and tonify the qi and blood.
5.Development and evaluation of a triplex RT-qPCR assay with internal references for detection of the Dengue and Zika viruses
Meng-Tao CAO ; Xiao-Yu HU ; Wei YANG ; Chun-Yuan LI ; Xiao-Li XU ; Rui-Wen REN ; Hong-Xia JIANG
Chinese Journal of Zoonoses 2024;40(6):537-543
A triplex RT-qPCR assay with human genes as internal references was established for detection of the Dengue and Zika viruses(DENV and ZIKV,respectively).The conserved regions of the four serotypes of DENV,along with the NS1 gene of ZIKV and the human β-actin gene,which is stably ex-pressed in various human tissues,were targeted by three sets of specific primers and probes.Standard plasmids for four se-rotypes of DENV,ZIKV,and β-actin were constructed as pos-itive controls.Optimal reaction conditions were determined through an L9(34)orthogonal experiment.The specificity,sensitivity,and coverage of the assay were verified and evalua-ted clinically,and the consistency was evaluated against a com-mercial kit for detection of DENV.The triplex RT-qPCR assay established exhibited no non-specific cross reactions with 12 similar arboviruses.The detection sensitivity for DENV and ZIKV were 2.99 and 2.18 copies/μL,respectively,and the intra-group and inter-group repeatability coefficients of variation were within 1.5%.As compared to the commercial kit,the proposed assay obtained positive results for 13 epidemic strains of DENV.Bland-Altman consistency analysis confirmed that the consistency of the detection results of clinical positive samples between the commercial kit and the proposed assay was 92.59%.The highly specific and sensitive triplex RT-qPCR assay with internal references is an effective tool for early and rapid differential identification of DENV and ZIKV.
6.Effects of Different Test Positions on Quantitative Muscle Strength of Wrist and Finger Flexor Muscle Groups and Its Standardization
Ze-Ren YANG ; Dong GAO ; Qing XIA ; Dan RAN ; Yan-Liang SHENG ; Wen-Tao XIA
Journal of Forensic Medicine 2024;40(3):237-244,253
Objective To explore the effects of different test positions on quantitative muscle strength of wrist and finger flexor muscle groups and to establish a standardized muscle strength test protocol for each muscle group.Methods Forty healthy subjects (12 males and 28 females) were recruited.A portable digital quantitative muscle strength tester,Micro FET2TM,was used to measure the flexor muscle strength of each finger and the wrist joint at the 30° extension,0° neutral,and 30° flexion,respectively.Palmar abduction strength of the thumb was measured at 30° and 60°,respectively.Ten subjects were randomly selected from the 40 subjects,and the quantitative muscle strength of each muscle group was tested again by the same operator after an interval of 10 to 15 days.Results Except for the fact that in males,there was no significant difference in flexor muscle strength of thumb and wrist joint between 30° of wrist extension and neutral 0° position,the muscle strength of the other fingers flexion and wrist palmar flexor showed the following characteristics:30° of wrist extension>neutral 0° posi-tion>30° of flexion,and the PAST was 30°>60°;The flexor muscle strength of all the subjects was thumb>index finger>middle finger>ring finger>little finger;All muscle strength values of male were greater than those of female,and the difference was statistically significant (P<0.05);There was no significant difference between the left and right side muscle strength values of all subjects (P>0.05).The reliability of muscle strength values measured at different times in 10 subjects was good.Conclu-sion The quantitative muscle strength of each muscle group of the hand and wrist is affected by the test position,and a standardized and uniformed test position should be adopted in the actual identification.Micro FET2TM has good reliability for hand and wrist quantitative muscle strength testing.The 30° ex-tension of the wrist can be used as the best standardized test position for the flexion muscle strength of each finger and wrist joint.The 30° position can be used as the best standardized test position for PAST.
7.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.
8.Potential components and mechanism of Liangxue Tuezi Mixture in treating Henoch-Schönlein purpura based on network pharmacology and metabolomics.
Wei-Xia LI ; Shuang XU ; Yu-Long CHEN ; Xiao-Yan WANG ; Hui ZHANG ; Ming-Liang ZHANG ; Wen-Juan NI ; Xian-Qing REN ; Jin-Fa TANG
China Journal of Chinese Materia Medica 2023;48(12):3327-3344
Ultra-performance liquid chromatography-quadrupole time of fight/mass spectrometry(UPLC-Q-TOF-MS) and UNIFI were employed to rapidly determine the content of the components in Liangxue Tuizi Mixture. The targets of the active components and Henoch-Schönlein purpura(HSP) were obtained from SwissTargetPrediction, Online Mendelian Inheritance in Man(OMIM), and GeneCards. A "component-target-disease" network and a protein-protein interaction(PPI) network were constructed. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the targets by Omishare. The interactions between the potential active components and the core targets were verified by molecular docking. Furthermore, rats were randomly assigned into a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups. Non-targeted metabolomics was employed to screen the differential metabolites in the serum, analyze possible metabolic pathways, and construct the "component-target-differential metabolite" network. A total of 45 components of Liangxue Tuizi Mixture were identified, and 145 potential targets for the treatment of HSP were predicted. The main signaling pathways enriched included resistance to epidermal growth factor receptor tyrosine kinase inhibitors, phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT), and T cell receptor. The results of molecular docking showed that the active components in Liangxue Tuizi Mixture had strong binding ability with the key target proteins. A total of 13 differential metabolites in the serum were screened out, which shared 27 common targets with active components. The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.
Animals
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Rats
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IgA Vasculitis/drug therapy*
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Network Pharmacology
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Molecular Docking Simulation
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Phosphatidylinositol 3-Kinases
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Metabolomics
9.Analysis of 7 cases of pediatric acute myeloid leukemia with DEK-NUP214 fusion gene.
Xiao Lan LI ; Li Peng LIU ; Yang WAN ; Fang LIU ; Xia CHEN ; Yuan Yuan REN ; Min RUAN ; Ye GUO ; Xiao Fan ZHU ; Wen Yu YANG
Chinese Journal of Pediatrics 2023;61(4):357-362
Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.
Adolescent
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Child
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Female
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Humans
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Male
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Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
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Chromosomal Proteins, Non-Histone/genetics*
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Cladribine/therapeutic use*
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Cytarabine/therapeutic use*
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Daunorubicin/therapeutic use*
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Etoposide/therapeutic use*
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Granulocyte Colony-Stimulating Factor/therapeutic use*
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Homoharringtonine/therapeutic use*
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Idarubicin/therapeutic use*
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Leukemia, Myeloid, Acute/genetics*
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Oncogene Proteins/genetics*
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Poly-ADP-Ribose Binding Proteins/genetics*
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Remission Induction
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Retrospective Studies
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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