1.Human AKR1A1 involves in metabolic activation of carcinogenic aristolochic acid Ⅰ
Zhenna GAO ; Xinyue YOU ; Weiying LIU ; Jiaying WU ; Jing XI ; Yiyi CAO ; Xiaohong ZHANG ; Xinyu ZHANG ; Yang LUAN
Chinese Journal of Pharmacology and Toxicology 2024;38(9):641-651
OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore-ductase(NR)and bioactivate aristolochic acid Ⅰ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS① Human-induced hepatocytes(hiHeps)and human bladder RT4 cells were used as tool cells and treated with AA-Ⅰ0,0.5,1.0 and 2 μmol·L-1 for 24 h.Cell viability was detected using the CCK-8 method,and the half maximal inhibition concentration(IC50)was calculated using the CCK-8 method and the level of DNA adduct production was calculated.②hiHeps and RT4 cells were treated with AKR inhibitor luteotin(0,5,10 and 25 μmol·L-1)+AA-Ⅰ 0.2 and 1.0 μmol·L-1 for 24 h,respectively,and the levels of DNA adducts were detected by a liquid chromatography-tandem mass spectrometer(LC-MS/MS).③hiHeps cells were incubated with 80 nmol·L-1 small interfering RNAs(si-AKRs)for 48 h and treated with AA-Ⅰ1.0 μmol·L-1 for 24 h.Real-time qualitative PCR(RT-qPCR)method was used to detect the mRNA expression of AKRs gene and LC-MS/MS technology was used to investigate the effect of specific AKR gene knockdown on DNA adduct levels.④500 nmol·L-1 human AKR recombinant proteins AKR1A1 and AA-Ⅰwere incubated in vitro under anaerobic conditions and the formation of AA-Ⅰ-DNA adducts was detected.RESULTS ①The IC50 of AA-Ⅰto hiHeps and RT4 cells was 1.9 and 0.42 μmol·L-1,respec-tively.The level of DNA adduct production of the two cell lines was significantly different(P<0.01).② Luteolin≥5 μmol·L-1 significantly inhibited the production of AA-Ⅰ-DNA adducts in both cells(P<0.05),and there was a concentration-dependent effect in hiHeps cells(P<0.01,R=0.84).③In the AKR family,the knockdown of AKR1A1 gene up to 80%inhibited the generation of AA-Ⅰ-DNA adducts by 30%-40%.④The AA-Ⅰ-DNA adducts were detected in the incubation of recombinant protein AKR1A1 and AA-Ⅰ under anaerobic conditions in vitro,approximately 1 adduct per 107 nucleotides.CONCLU-SION AKR1A1 is involved in AA-Ⅰ bioactivation,providing a reference for elucidation of the carcino-genic mechanism of AA-Ⅰ.
2.Surveillance of antifungal resistance in clinical isolates of Candida spp.in East China Invasive Fungal Infection Group from 2018 to 2022
Dongjiang WANG ; Wenjuan WU ; Jian GUO ; Min ZHANG ; Huiping LIN ; Feifei WAN ; Xiaobo MA ; Yueting LI ; Jia LI ; Huiqiong JIA ; Lingbing ZENG ; Xiuhai LU ; Yan JIN ; Jinfeng CAI ; Wei LI ; Zhimin BAI ; Yongqin WU ; Hui DING ; Zhongxian LIAO ; Gen LI ; Hui ZHANG ; Hongwei MENG ; Changzi DENG ; Feng CHEN ; Na JIANG ; Jie QIN ; Guoping DONG ; Jinghua ZHANG ; Wei XI ; Haomin ZHANG ; Rong TANG ; Li LI ; Suzhen WANG ; Fen PAN ; Jing GAO ; Lu JIANG ; Hua FANG ; Zhilan LI ; Yiqun YUAN ; Guoqing WANG ; Yuanxia WANG ; Liping WANG
Chinese Journal of Infection and Chemotherapy 2024;24(4):402-409
Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33%of which were isolated from sterile body sites,mainly from blood(38.86%)and pleural effusion/ascites(10.21%).The predominant species of Candida were Candida albicans(44.51%),followed by Candida parapsilosis complex(19.46%),Candida tropicalis(13.98%),Candida glabrata(10.34%),and other Candida species(0.79%).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62%).Only 2.97%of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61%and a resistance rate of 9.42%to fluconazole,and susceptibility rates above 90%to other drugs.Candida glabrata had a SDD rate of 92.01%and a resistance rate of 7.99%to fluconazole,resistance rates of 32.27%and 48.24%to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90%to other drugs.Candida tropicalis had resistance rates of 29.55%and 26.24%to fluconazole and voriconazole,respectively,resistance rates of 76.60%and 21.99%to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36%to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.
3.Background, design, and preliminary implementation of China prospective multicenter birth cohort
Si ZHOU ; Liping GUAN ; Hanbo ZHANG ; Wenzhi YANG ; Qiaoling GENG ; Niya ZHOU ; Wenrui ZHAO ; Jia LI ; Zhiguang ZHAO ; Xi PU ; Dan ZHENG ; Hua JIN ; Fei HOU ; Jie GAO ; Wendi WANG ; Xiaohua WANG ; Aiju LIU ; Luming SUN ; Jing YI ; Zhang MAO ; Zhixu QIU ; Shuzhen WU ; Dongqun HUANG ; Xiaohang CHEN ; Fengxiang WEI ; Lianshuai ZHENG ; Xiao YANG ; Jianguo ZHANG ; Zhongjun LI ; Qingsong LIU ; Leilei WANG ; Lijian ZHAO ; Hongbo QI
Chinese Journal of Perinatal Medicine 2024;27(9):750-755
China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.
4.Evaluation of prophylactic use of metal clips after cold resection of 6-10 mm intestinal polyps
Zhongxin SUN ; Can WU ; Mei YANG ; Li LIU ; Liu LIU ; Zhengkui ZHOU ; Weidong XI ; Jing SHAN ; Lin JIANG ; Yu LEI ; Xiaobin SUN
Chinese Journal of Digestive Endoscopy 2024;41(7):550-554
Objective:To investigate whether prophylactic use of metal clips is necessary after cold snare polypectomy (CSP) of colorectal polyps of 6-10 mm.Methods:A total of 200 patients with 6-10 mm polyps that met the criteria of cold snare resection in Chengdu Third People's Hospital from 15 February 2022 to 30 May 2022 were randomly divided into two groups: a group that received preventive metal clip treatment and an observation group. Age, gender, body mass index (BMI), Boston score, endoscopy entry time, wound size, operation time, intraoperative bleeding time, postoperative delayed bleeding rate and cost between the two groups were compared and analyzed.Results:Ninety-eight patients in the metal clip group had 122 polyps removed, and 97 patients in the observation group had 119 polyps removed. There was no significant difference in the age, gender, BMI, Boston score, endoscopy entry time or wound size between the two groups. There were significant differences in the operation time (171.03±90.78 s VS 69.81±43.26 s, t=2.266, P=0.010), intraoperative bleeding time (19.98±17.37 s VS 29.16±17.56 s, t=-2.875, P=0.006) and surgery cost (571.63±110.92 yuan VS 366.32±13.2 yuan, t=18.102, P<0.001) between the metal clip group and the observation group. There was no significant difference in the delayed bleeding incidence[0.0%(0/98)VS 1.0%(1/97), P=0.497]between the two groups. Conclusion:For patients with continuous bleeding time <60 seconds after CSP of 6-10 mm colonic polyps, the prophylactic use of metal clips may reduce the bleeding time, but may increase the operation time and cost. Metal clips have little effect on preventing postoperative complications.
5.Consistency evaluation of the Kimura-Takemoto classification and operative link for gastritis assessment in risk stratification of gastric cancer after Helicobacter pylori eradication
Chengyao WANG ; Linlin SHAO ; Wenkun LI ; Rui CHENG ; Xi ZHANG ; Zheng ZHANG ; Peng LI ; Shutian ZHANG ; Jing WU
Chinese Journal of Digestion 2024;44(5):308-313
Objective:To assess the correlation and consistency between the cancer risk-oriented endoscopic Kimura-Takemoto classification and the operative link for gastritis assessment (OLGA) in risk stratification of gastric cancer in patients with chronic gastritis after Helicobacter pylori ( H. pylori) eradication. Methods:From January 1, 2018 to October 31, 2021, 97 patients with chronic gastritis who successfully underwent H. pylori eradication at Beijing Friendship Hospital affiliated to Capital Medical University were selected. During the follow-up period, all patients underwent standardized magnifying endoscopy to assess gastric mucosal atrophy with the Kimura-Takemoto classification, which was classified as no or mild atrophy, moderate atrophy, and severe atrophy. Additionally, according to the new Sydney staging system, endoscopic biopsies were conducted at 5 sites of the patients to classify into OLGA stages 0, Ⅰ, Ⅱ, Ⅲ, or Ⅳ. Spearman rank correlation analysis and Kappa consistency test were performed to evaluate the correlation and consistency between the 2 evaluation systems, respectively. Area under the curve (AUC) of the receiver operating characteristic curve was used to calculate the predictive ability of the grading of gastric mucosal atrophy under endoscopy in high-risk histological staging. Furthermore, multivariate logistic regression analysis was used to assess factors influencing the consistency of the 2 evaluation systems. Chi-square test or Fisher′s exact test were used for statistical analysis. Results:Longitudinal follow-up was completed in 97 cases, with a follow-up time of (37.38±13.18) months after H. pylori eradication. The proportion of OLGA stage Ⅲ to Ⅳ in patients with no or mild atrophy (21.7%, 10/46) was lower than that in patients with moderate and severe atrophy (63.0%, 29/46 and 5/5, respectively), and the differences were statistically significant( χ2=16.07 and 13.30, both P<0.001). However, there was no significant difference in distribution of OLGA staging between patients with moderate atrophy and patients with severe atrophy (all P>0.05). The consistency rate of high-risk assessment for gastric cancer between the 2 evaluation systems was 73.2% (71/97). The correlation between the Kimura-Takemoto classification and OLGA staging was moderate ( r=0.47, 95% confidence interval(95% CI) 0.30 to 0.61, P<0.001). The result of consistency test indicated that the consistency of the 2 evaluation systems was moderate, and the Kappa value was 0.46 (95% CI 0.29 to 0.64, P<0.001). For patients with chronic gastritis after H. pylori eradication, the sensitivity of Kimura-Takemoto classification of moderate to severe atrophy under endoscopy in identifying high-risk of OLGA stages was 77.21% (95% CI 62.16% to 88.53%), the specificity was 69.81% (95% CI 55.66% to 81.66%), and the AUC was 0.735 (95% CI 0.636 to 0.820, P<0.01). As the time after H. pylori eradication increased (post- H. pylori eradication less than 18, 18 to 36, and more than 36 months), the consistency of atrophy assessment between the Kimura-Takemoto classification and OLGA staging reduced (7/8, 84.4% (27/32), 64.9% (37/57), respectively), and the difference was statistically significant ( χ2=4.36, P=0.037). The result of multivariate logistic regression analysis revealed that the time after H. pylori eradication more than 36 months ( OR=3.443, 95% CI 1.117 to 10.614, P=0.031) and gastric ulcer ( OR=3.928, 95% CI 1.177 to 13.110, P=0.026) were independent factors influencing the consistency between the Kimura-Takemoto classification and OLGA staging. Conclusions:The endoscopic and histological changes of chronic gastritis after eradication of H. pylori are consistent. Within short period after H. pylori eradication (no more than 36 months), the sensitivity of high-risk classification under endoscopy is high and the specificity is moderate, which can predict high-risk histological staging to a certain degree.
6.Practice and reflection on strengthening ideological and political work in public hospitals from the per-spective of high-quality development
Jing JIAO ; Chun GUAN ; Lin DONG ; Xin LUO ; Li HUANG ; Xi WU ; Wenli DUAN
Modern Hospital 2024;24(7):1031-1033
Ideological and political work is the fine tradition,distinct characteristic,and political advantage of the Com-munist Party of China,and it is the lifeline of all work.This article,based on literature research and practical experience,ex-pounds the important significance of ideological and political work for the high-quality development of public hospitals,analyzes the weaknesses of current ideological and political work,focuses on strengthening ideals and beliefs,sharpening the initial aspira-tion of serving the people,and cultivating high-quality talents,and explores the practical path of strengthening ideological and po-litical work in hospitals in the new era.It summarizes the working methods of"three focuses,three combinations,and three unifi-cations,"providing strong impetus for the high-quality development of hospitals.
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.Implementation of surveillance,prevention and control of healthcare-asso-ciated infection in maternal and child healthcare institutions:A nation-wide investigation report
Shuo LI ; Xi YAO ; Hui-Xue JIA ; Wei-Guang LI ; Xun HUANG ; Shu-Mei SUN ; Xi CHENG ; Qing-Lan MENG ; Xiang ZHANG ; Jing-Ping ZHANG ; Ya-Wei XING ; Qing-Qing JIANG ; Lian-Xuan WU ; Bing-Li ZHANG ; Xiao-Jing LIU ; Liu-Yi LI
Chinese Journal of Infection Control 2024;23(3):323-329
Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24%of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66%,85.96%,80.77%,and 74.19%,respectively.51.22%MCH institutions adopted information surveillance system on HAI cases.94.31%MCH institutions carried out surveillance on hand hygiene compliance.Over 90%MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54%MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90%MCH insti-tutions established three-level pre-examination triage systems.86.18%set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50%.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.
9.Pharmacokinetics of JS026 and JS026-JS016 for single intravenous administration in healthy volunteers
Yan TIAN ; Hui-Jing YE ; Jing-Jing WANG ; Nan-Yang LI ; Juan MA ; Xi TAN ; Fan WU ; Jie WANG ; Shu-Yan YU ; Xiao-Jie WU ; Jin-Jie HE ; Jing ZHANG ; Wen-Hong ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(15):2251-2255
Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.
10.The predictive value of a nomogram model based on aspartate aminotransferase-platelet ratio index for hepatocellular carcinoma recurrence after radiofrequency ablation
Yaxiang JI ; Jing XI ; Chunyan LIU ; Ping WU ; Xiaolan ZHANG ; Qian SONG
Journal of Interventional Radiology 2024;33(1):38-43
Objective To investigate the relationship between aspartate aminotransferase-platelet ratio index(APRI)and hepatocellular carcinoma(HCC)recurrence after radiofrequency ablation(RFA),and to construct a nomogram model for predicting the prognosis.Methods The clinical data of a total of 204 patients,whose initial diagnosis was HCC and received RFA at the Wujin Hospital Affiliated to Jiangsu University of China between January 2017 and December 2020,were retrospectively analyzed.The optimal cut-off value of APRI was determined using receiver operating characteristic(ROC)curve.Kaplan-Meier curves were plotted to estimate the recurrence-free survival(RFS)of high-APRI group patients and low-APRI group patients.The independent predictors of HCC recurrence after RFA were identified by using univariate and multivariate Cox regression analysis,and significant variables were selected to construct a nomogram model.The predictive ability of the nomogram model for HCC recurrence was evaluated by the consistency index(C-index)and calibration curves.Results The incidence of HCC recurrence after RFA was 57.4%(117/204),the optimal cut-off value of APRI for predicting HCC recurrence was 0.501,and the area under curve(AUC)value was 0.678(95%CI=0.603-0.752).High-APRI group(≥0.501)had 121 patients and low-APRI group(<0.501)had 83 patients.High APRI index was significantly correlated with low RFS(χ2=12.929,P<0.01).The univariate and multivariate Cox regression analysis revealed that the number of tumors(HR=1.541,95%CI=1.039-2.286,P=0.031),maximum tumor diameter(HR=1.461,95%CI=1.011-2.112,P=0.044),serum AFP level(HR=2.286,95%CI=1.576-3.318,P<0.01)and APRI index(HR=1.873,95%CI=1.257-2.790,P=0.002)were the independent risk factors for HCC recurrence.Based on the above four variables,a nomogram model for predicting HCC recurrence after RFA was constructed,the C-index was 0.769(95%CI=0.676-0.862),and the AUC values for 1-,2-,and 3-year RFS prediction were 0.707,0.719,and 0.707,respectively.The calibration curves showed that a good consistency existed between the predicted probability and actual probability.Conclusion The nomogram model based on APRI and tumor biological characteristics has an excellent predictive ability for HCC recurrence after RFA.(J Intervent Radiol,2024,32:38-43)

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