1. 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.
2.Analysis of laboratory indicators related to female pattern hair loss
Xifei QIAN ; Zhewei HUANG ; Chongxiang FAN ; Jingyi TU ; Jue HOU ; Hanxiao CHENG ; Jufang ZHANG
Chinese Journal of Plastic Surgery 2024;40(1):34-40
Objective:To investigate the effect of laboratory indicators on hair loss in patients with female pattern hair loss (FPHL).Methods:Patients with FPHL who visited the Outpatient Clinic of the Department of Medical Aesthetics in Hangzhou First People’s Hospital from November 2022 to November 2023 were selected as the study group, and healthy women who matched the age of the study group in the physical examination center during the same period were selected as the control group. The general information of the patient was recorded, and was also tested by trichoscopy to rule out other patterns of alopecia. Representative indicators including testosterone, dehydroepiandrosterone sulfate(DHEA-S), thyroid-stimulating hormone, 25-hydroxyvitamin D, and serum ferritin were selected from laboratory tests for further analysis. Otherwise, the proportion of deficiency in vitamin D(<20 ng/ml) was calculated based on 25-hydroxyvitamin D levels (number of deficiency cases/total number of cases in each group×100%). Count data were presented as samples (percentages), and chi-square test was used for comparison between groups. Normally distributed continuous data were presented with Mean±SD, independent samples t-test was used for comparison between groups, M( Q1, Q3) was used for non-normally distributed continuous data, and Wilcoxon rank-sum test was used for comparison between groups. Multivariate logistic regression was used to analyze the influencing factors of FPHL. P<0.05 was statistically significant. Results:A total of 37 patients were selected in both groups. The mean age was (28.8±1.3) years in the study group and (29.6±0.9) years in the control group ( t=0.49, P=0.625). The body mass index was (22.8±0.4) kg/m 2 in the study group, and (23.5±0.3) kg/m 2 in the control group ( t=1.26, P=0.211). The testosterone level was 0.58 (0.49, 0.79) nmol/L in the study group, and 0.54 (0.50, 0.78) nmol/L in the control group( Z=1.42, P=0.157). The level of DHEA-S was 6.21 (5.18, 9.60) μmol/L in the study group, and 6.20 (5.20, 9.34) μmol/L in the control group ( Z=2.75, P=0.006). The level of thyroid-stimulating hormone was 2.56 (1.55, 3.66) mU/L in the study group and 1.49 (1.05, 2.65) mU/L in the control group ( Z=2.51, P=0.012). The level of 25-hydroxyvitamin D was 15.44 (11.80, 21.20) ng/ml in the study group, and the level of 25-hydroxyvitamin D was 20.32 (12.07, 21.20) ng/ml in the control group ( Z=2.30, P=0.021), and the proportion of 25-hydroxyvitamin D deficiency in the study group was 64.9% (24/37), which was higher than that in the control group [40.5% (15/37)] ( χ2=4.39, P=0.036). The serum ferritin level was 64.44 (39.47, 133.45) μg/L in the study group and 67.75 (52.63, 143.83) μg/L in the control group ( Z=0.70, P=0.484). The results of multivariate logistic regression analysis showed that the risk of FPHL was increased by the high level of DHEA-S and thyroid-stimulating hormone, and the low level of 25-hydroxyvitamin D (all P<0.05). Conclusion:Abnormal level of DHEA-S, thyroid-stimulating hormone, and 25-hydroxyvitamin D may be risk factors for FPHL.
3.Design and Application of an Artificial Intelligence Follow-up System for Gestational Hypertension
Xinyi HUANG ; Xiaoping ZHOU ; Jianjun GUO ; Rongrong SHENG ; Zhongmin WANG ; Jue WANG ; Nana YANG ; Yin YIN
Journal of Medical Informatics 2024;45(1):89-92
Purpose/Significance Gestational hypertension poses a serious threat to maternal health.Artificial intelligence(AI)fol-low-up and management systems contributes to the health of gestational hypertension.Method/Process The paper establishes an AI fol-low-up system for gestational hypertension based on big data technology and data platforms,including modules such as patient informa-tion management,follow-up data management,follow-up plan management,and patient course management.Result/Conclusion The follow-up system can assist doctors in understanding changes in patients'diseases and meet the hospital's follow-up management re-quirements for gestational hypertension in outpatient clinics.
4.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.
5.Clinical Study on Bazhen Decoction Combined with Traumatic Medicated Gauze in the Treatment of Diabetic Foot Ulcer of Qi-Blood Deficiency Syndrome
Sheng-Han HUANG ; Guang-Li LI ; Si-Yun LI ; Jue ZHANG ; Ai-Sheng WEI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(11):2943-2948
Objective To observe the clinical efficacy of Bazhen Decoction combined with traumatic medicated gauze(prepared mainly with the herbs of Scutellariae Radix,Phellodendri Chinensis Cortex and Sanguisorbae Radix)in the treatment of patients with diabetic foot ulcer(DFU)of qi-blood deficiency syndrome.Methods A total of 42 cases of DFU patients with qi-blood deficiency syndrome were randomly divided into a control group and an observation group,with 21 cases in each group.The control group was given basic western medicine treatment combined with external application of traumatic medicated gauze on wound surface,while the observation group was treated with Bazhen Decoction orally on the basis of treatment for the control group,and the treatment course of both groups covered four weeks.The changes of wound area,traditional Chinese medicine(TCM)syndrome scores,ankle-brachial index(ABI),and serum levels of fibrinogen(FIB),C-reactive protein(CRP),tumor necrosis factor α(TNF-α)in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety in the two groups were compared.Results(1)After four weeks of treatment,the total effective rate in the observation group was 95.24%(20/21)and that in the control group was 85.71%(18/21),and the intergroup comparison(by rank sum test)showed that the clinical efficacy in the observation group was significantly superior to that in the control group(P<0.05).(2)After treatment,the wound area and TCM syndrome scores in the two groups were significantly improved compared with those before treatment(P<0.05),and the improvement of the wound area and TCM syndrome score in the observation group was significantly superior to that in the control group(P<0.05).(3)After treatment,ABI in the two groups was increased when compared with that before treatment(P<0.05),and the improvement of ABI in the observation group was significantly superior to that in the control group(P<0.05).(4)After treatment,the levels of serum CRP,TNF-α and FIB in the two groups were all decreased compared with those before treatment(P<0.05),and the improvement of the serum levels in the observation group was significantly superior to that in the control group(P<0.05).(5)During the treatment,there were no significant adverse reactions occurring in the two groups,with high safety.Conclusion Bazhen Decoction combined with traumatic medicated gauze exerts certain effect in the treatment of DFU patients with qi-blood deficiency syndrome.The combined therapy is effective on improving the coagulation function and lower limb ischemia,reducing the levels of inflammatory factors,and relieving the inflammatory reaction,without obvious adverse reactions.
6.Analysis of laboratory indicators related to female pattern hair loss
Xifei QIAN ; Zhewei HUANG ; Chongxiang FAN ; Jingyi TU ; Jue HOU ; Hanxiao CHENG ; Jufang ZHANG
Chinese Journal of Plastic Surgery 2024;40(1):34-40
Objective:To investigate the effect of laboratory indicators on hair loss in patients with female pattern hair loss (FPHL).Methods:Patients with FPHL who visited the Outpatient Clinic of the Department of Medical Aesthetics in Hangzhou First People’s Hospital from November 2022 to November 2023 were selected as the study group, and healthy women who matched the age of the study group in the physical examination center during the same period were selected as the control group. The general information of the patient was recorded, and was also tested by trichoscopy to rule out other patterns of alopecia. Representative indicators including testosterone, dehydroepiandrosterone sulfate(DHEA-S), thyroid-stimulating hormone, 25-hydroxyvitamin D, and serum ferritin were selected from laboratory tests for further analysis. Otherwise, the proportion of deficiency in vitamin D(<20 ng/ml) was calculated based on 25-hydroxyvitamin D levels (number of deficiency cases/total number of cases in each group×100%). Count data were presented as samples (percentages), and chi-square test was used for comparison between groups. Normally distributed continuous data were presented with Mean±SD, independent samples t-test was used for comparison between groups, M( Q1, Q3) was used for non-normally distributed continuous data, and Wilcoxon rank-sum test was used for comparison between groups. Multivariate logistic regression was used to analyze the influencing factors of FPHL. P<0.05 was statistically significant. Results:A total of 37 patients were selected in both groups. The mean age was (28.8±1.3) years in the study group and (29.6±0.9) years in the control group ( t=0.49, P=0.625). The body mass index was (22.8±0.4) kg/m 2 in the study group, and (23.5±0.3) kg/m 2 in the control group ( t=1.26, P=0.211). The testosterone level was 0.58 (0.49, 0.79) nmol/L in the study group, and 0.54 (0.50, 0.78) nmol/L in the control group( Z=1.42, P=0.157). The level of DHEA-S was 6.21 (5.18, 9.60) μmol/L in the study group, and 6.20 (5.20, 9.34) μmol/L in the control group ( Z=2.75, P=0.006). The level of thyroid-stimulating hormone was 2.56 (1.55, 3.66) mU/L in the study group and 1.49 (1.05, 2.65) mU/L in the control group ( Z=2.51, P=0.012). The level of 25-hydroxyvitamin D was 15.44 (11.80, 21.20) ng/ml in the study group, and the level of 25-hydroxyvitamin D was 20.32 (12.07, 21.20) ng/ml in the control group ( Z=2.30, P=0.021), and the proportion of 25-hydroxyvitamin D deficiency in the study group was 64.9% (24/37), which was higher than that in the control group [40.5% (15/37)] ( χ2=4.39, P=0.036). The serum ferritin level was 64.44 (39.47, 133.45) μg/L in the study group and 67.75 (52.63, 143.83) μg/L in the control group ( Z=0.70, P=0.484). The results of multivariate logistic regression analysis showed that the risk of FPHL was increased by the high level of DHEA-S and thyroid-stimulating hormone, and the low level of 25-hydroxyvitamin D (all P<0.05). Conclusion:Abnormal level of DHEA-S, thyroid-stimulating hormone, and 25-hydroxyvitamin D may be risk factors for FPHL.
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.Clinical observation of acupuncture combined with medication for mild-to-moderate depression
Abulikemu DILINUER ; Penpat ITTIPALANUKUL ; Pengtao WU ; Xinyi HU ; Aijia ZHANG ; Yuwei HUANG ; Ruiqi CHE ; Yi WANG ; Zhihai HU ; Jue HONG
Journal of Acupuncture and Tuina Science 2024;22(5):400-409
Objective:To discuss the clinical efficacy and plausible mechanism of Tiao Yang Qu Xie(regulating Yang to eliminate pathogenic factors)needling method plus paroxetine in treating mild-to-moderate depression. Methods:Sixty-six patients with mild-to-moderate depression were divided into an observation group and a control group using the random number table method,each consisting of 33 cases.Another 25 healthy subjects were recruited as a healthy group.The control group took oral paroxetine tablets for treatment,and the observation group received additional acupuncture treatment 3 times weekly.Both groups underwent 4-week treatment.Before treatment,after 2-week and 4-week treatment,and 2 weeks after treatment(follow-up),the patients were assessed using the Hamilton depression scale-17-item(HAMD-17),self-rating depression scale(SDS),self-rating anxiety scale(SAS),and traditional Chinese medicine(TCM)pattern element identification scale for depression.The two groups each randomly contributed 25 cases to detect the protein content of brain-derived neurotrophic factor(BDNF)before treatment and after 4-week treatment,and compared with the healthy group. Results:After 2-week treatment,the markedly effective and total effective rates were significantly higher in the observation group than in the control group(P<0.05);after 4-week treatment,the observation group significantly surpassed the control group in comparing the markedly effective rate(P<0.05).After 2 and 4 weeks of treatment and at the follow-up,the HAMD-17 total score and sleep disorder factor score were lower in the observation group than in the control group(P<0.05);the anxiety-somatic score was lower in the observation group than in the control group after 2-week treatment(P<0.05).After 2 and 4 weeks of treatment and at the follow-up,the observation group was lower than the control group in comparing the scores of SDS,SAS,and TCM pattern element identification scale for depression(P<0.05).After 4-week treatment,the observation group had an increased serum BDNF protein content,higher than that in the control group(P<0.05)and had no significant difference compared to the healthy group(P>0.05). Conclusion:Compared to the use of oral paroxetine alone,acupuncture plus paroxetine can produce more significant efficacy in treating mild-to-moderate depression and act faster in improving sleep disorder and anxiety-somatic symptoms;increasing the serum BDNF protein content may be a part of the mechanism underlying its antidepressant actions.
9.Application of proanthocyanidin in the treatment and repair of deep caries
GAO Ying ; WANG Jue ; TAO Lu ; YAO Jingjing ; YU Jinling ; HUANG Handan ; YANG Liuqing ; LIU Zhihui
Journal of Prevention and Treatment for Stomatological Diseases 2023;31(7):518-523
Proanthocyanidin (PA), as a kind of natural plant polyphenol, have a variety of biological functions, such as promoting remineralization, inducing collagen cross-linking, inhibiting protease activity and inhibiting bacteria. Therefore, PA could be broadly used in the clinical application of treatment and repair of deep caries in the future; for example, PA could promote dentin remineralization, improve resin-dentin bonding durability and improve the dentin acid erosion effect. This application potential of PA arises from several features, firstly, PA can not only promote dentin remineralization on its own or with other remineralizers but also exhibits antibacterial effects, which can inhibit acid production while reducing the formation of cariogenic pathogens and their biofilms. Based on the above features, PA can reduce the incidence of caries disease; thus, PA improves deep caries and long-term effects after treatment. In addition, PA added to adhesives or etch agents can improve the etching and bonding effect of dentin by inducing collagen cross-linking and inhibiting protease activity, thus achieving the ultimate goal of improving the bonding performance of deep caries. This paper summarizes recent progress of research on PA for the treatment and repair of deep caries, including the promotion of dentin remineralization and antibacterial activity as well as the improvement in dentin bonding and acid etching effect, to provide a more comprehensive reference for treating and restoring deep caries in clinical practice.
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
;
Aged


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