1.Percutaneous coronary intervention vs . medical therapy in patients on dialysis with coronary artery disease in China.
Enmin XIE ; Yaxin WU ; Zixiang YE ; Yong HE ; Hesong ZENG ; Jianfang LUO ; Mulei CHEN ; Wenyue PANG ; Yanmin XU ; Chuanyu GAO ; Xiaogang GUO ; Lin CAI ; Qingwei JI ; Yining YANG ; Di WU ; Yiqiang YUAN ; Jing WAN ; Yuliang MA ; Jun ZHANG ; Zhimin DU ; Qing YANG ; Jinsong CHENG ; Chunhua DING ; Xiang MA ; Chunlin YIN ; Zeyuan FAN ; Qiang TANG ; Yue LI ; Lihua SUN ; Chengzhi LU ; Jufang CHI ; Zhuhua YAO ; Yanxiang GAO ; Changan YU ; Jingyi REN ; Jingang ZHENG
Chinese Medical Journal 2025;138(3):301-310
BACKGROUND:
The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China.
METHODS:
This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences.
RESULTS:
Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n = 278] vs . 43.7% [ n = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses.
CONCLUSION
This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans
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Percutaneous Coronary Intervention/methods*
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Male
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Female
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Coronary Artery Disease/drug therapy*
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Retrospective Studies
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Renal Dialysis/methods*
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Middle Aged
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Aged
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China
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Proportional Hazards Models
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Treatment Outcome
2.Association of higher serum follicle-stimulating hormone levels with successful microdissection testicular sperm extraction outcomes in nonobstructive azoospermic men with reduced testicular volumes.
Ming-Zhe SONG ; Li-Jun YE ; Wei-Qiang XIAO ; Wen-Si HUANG ; Wu-Biao WEN ; Shun DAI ; Li-Yun LAI ; Yue-Qin PENG ; Tong-Hua WU ; Qing SUN ; Yong ZENG ; Jing CAI
Asian Journal of Andrology 2025;27(3):440-446
To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans
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Male
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Azoospermia/surgery*
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Sperm Retrieval/statistics & numerical data*
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Adult
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Follicle Stimulating Hormone/blood*
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Retrospective Studies
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Testis/pathology*
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Microdissection
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Organ Size
3.Beyond cancer: The potential application of CD47-based therapy in non-cancer diseases.
Wei-Qing DENG ; Zi-Han YE ; Zhenghai TANG ; Xiao-Lei ZHANG ; Jin-Jian LU
Acta Pharmaceutica Sinica B 2025;15(2):757-791
CD47 is an immune checkpoint widely regarded as a 'don't eat me' signal. CD47-based anti-cancer therapy has received considerable attention, with a significant number of clinical trials conducted. While anti-cancer therapies based on CD47 remain a focal point of interest among researchers, it is noteworthy that an increasing number of studies have found that CD47-based therapy ameliorated the pathological status of non-cancer diseases. This review aims to provide an overview of the recent progress in comprehending the role of CD47-based therapy in non-cancer diseases, including diseases of the circulatory system, nervous system, digestive system, and so on. Furthermore, we sought to delineate the promising mechanisms of CD47-based therapy in treating non-cancer diseases. Our findings suggest that CD47-based agents may exert their effect by regulating phagocytosis, regulating T cells, dendritic cells, and neutrophils, and regulating the secretion of cytokines and chemokines. Additionally, we put forward the orientation of further research to bring to light the potential of CD47 and its binding partners as a target in non-cancer diseases.
4.Gallstones, cholecystectomy, and cancer risk: an observational and Mendelian randomization study.
Yuanyue ZHU ; Linhui SHEN ; Yanan HUO ; Qin WAN ; Yingfen QIN ; Ruying HU ; Lixin SHI ; Qing SU ; Xuefeng YU ; Li YAN ; Guijun QIN ; Xulei TANG ; Gang CHEN ; Yu XU ; Tiange WANG ; Zhiyun ZHAO ; Zhengnan GAO ; Guixia WANG ; Feixia SHEN ; Xuejiang GU ; Zuojie LUO ; Li CHEN ; Qiang LI ; Zhen YE ; Yinfei ZHANG ; Chao LIU ; Youmin WANG ; Shengli WU ; Tao YANG ; Huacong DENG ; Lulu CHEN ; Tianshu ZENG ; Jiajun ZHAO ; Yiming MU ; Weiqing WANG ; Guang NING ; Jieli LU ; Min XU ; Yufang BI ; Weiguo HU
Frontiers of Medicine 2025;19(1):79-89
This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans
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Mendelian Randomization Analysis
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Gallstones/complications*
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Female
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Male
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Cholecystectomy/statistics & numerical data*
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Middle Aged
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Risk Factors
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Aged
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Adult
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Neoplasms/etiology*
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Stomach Neoplasms/epidemiology*
5.The surgical results and accuracy evaluation of virtual surgical planning in segmental Le FortⅠ surgery
Yiyuan WEI ; Xiaoshuang SUN ; Qing ZHAO ; Yifan WU ; Han GE ; Bin YE ; Jihua LI
Chinese Journal of Plastic Surgery 2024;40(3):264-272
Objective:In this retrospective study, the accuracy and outcomes of segmental Le Fort I surgery with the aid of 3D-printed surgical templates and occlusal splints and dental model surgery were evaluated.Methods:Clinical data of patients receiving segmental Le Fort I surgery in the Department of Orthognathic and Temporo-Mandibular Joint Surgery of West China Stomatological Hospital of Sichuan University from January 2014 to June 2019 were retrospectively analyzed. The accuracy of virtual surgical planning(VSP) and the difference between VSP and dental model surgery were evaluated by postoperative complications, color distance maps, and quantitative accuracy analysis.The amount of surgical displacement of the maxilla in the three-dimensional direction before and after surgery, the occurrence of postoperative complications and the patients'satisfaction survey were analyzed in both groups. Paired t-tests were used for the linear distance and angle between the preoperative design model and the final virtual surgery model in the digital surgery group. Independent samples t-test was used for each marker point’s preoperative and postoperative displacements in the three-dimensional direction between the digital surgery group and the dental model group. The proportion of postoperative complications in the 2 groups was tested using the Pearson chi-square test, and the difference was considered statistically significant at P<0.05. Results:There were 129 patients in the digital surgery group, 35 males and 94 females, aged (24.5±6.5) years, and 92 patients in the dental model surgery group, 28 males and 64 females, aged (27.7±5.4) years.The overall mean linear difference was 1.23±0.35 mm, and the overall mean angular difference was 2.48°±0.31°. The vertical displacement of U3R, U6L in the digital surgery group was (6.72±1.57)mm and (4.73±2.07)mm. The vertical displacement of U3R, U6L in the group of dental model surgery was (4.07±2.14)mm and (1.62±1.82)mm.The significant deviation difference in U3R-Y and U6L-Y between two groups could be detected. The complications in two groups showed a significant difference. Except for one case of root injury, there was no serious complication recorded in the digital surgery group. However, there were three cases of palatal fistulas, four cases of root injury and two cases of bone dehiscence in the dental model group. 94.5% of patients in the digital surgery group are satisfied with the surgical results, while 89.1% in the dental model group.Conclusion:Compared with dental model surgery, segmental Le Fort I surgery is highly accurate under the guidance of surgical templates and occlusal splint which has better postoperative results and effectively reduces the occurrence of surgical complications.
6.The surgical results and accuracy evaluation of virtual surgical planning in segmental Le FortⅠ surgery
Yiyuan WEI ; Xiaoshuang SUN ; Qing ZHAO ; Yifan WU ; Han GE ; Bin YE ; Jihua LI
Chinese Journal of Plastic Surgery 2024;40(3):264-272
Objective:In this retrospective study, the accuracy and outcomes of segmental Le Fort I surgery with the aid of 3D-printed surgical templates and occlusal splints and dental model surgery were evaluated.Methods:Clinical data of patients receiving segmental Le Fort I surgery in the Department of Orthognathic and Temporo-Mandibular Joint Surgery of West China Stomatological Hospital of Sichuan University from January 2014 to June 2019 were retrospectively analyzed. The accuracy of virtual surgical planning(VSP) and the difference between VSP and dental model surgery were evaluated by postoperative complications, color distance maps, and quantitative accuracy analysis.The amount of surgical displacement of the maxilla in the three-dimensional direction before and after surgery, the occurrence of postoperative complications and the patients'satisfaction survey were analyzed in both groups. Paired t-tests were used for the linear distance and angle between the preoperative design model and the final virtual surgery model in the digital surgery group. Independent samples t-test was used for each marker point’s preoperative and postoperative displacements in the three-dimensional direction between the digital surgery group and the dental model group. The proportion of postoperative complications in the 2 groups was tested using the Pearson chi-square test, and the difference was considered statistically significant at P<0.05. Results:There were 129 patients in the digital surgery group, 35 males and 94 females, aged (24.5±6.5) years, and 92 patients in the dental model surgery group, 28 males and 64 females, aged (27.7±5.4) years.The overall mean linear difference was 1.23±0.35 mm, and the overall mean angular difference was 2.48°±0.31°. The vertical displacement of U3R, U6L in the digital surgery group was (6.72±1.57)mm and (4.73±2.07)mm. The vertical displacement of U3R, U6L in the group of dental model surgery was (4.07±2.14)mm and (1.62±1.82)mm.The significant deviation difference in U3R-Y and U6L-Y between two groups could be detected. The complications in two groups showed a significant difference. Except for one case of root injury, there was no serious complication recorded in the digital surgery group. However, there were three cases of palatal fistulas, four cases of root injury and two cases of bone dehiscence in the dental model group. 94.5% of patients in the digital surgery group are satisfied with the surgical results, while 89.1% in the dental model group.Conclusion:Compared with dental model surgery, segmental Le Fort I surgery is highly accurate under the guidance of surgical templates and occlusal splint which has better postoperative results and effectively reduces the occurrence of surgical complications.
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.The"suppressing wood-supporting earth"theory-based air moxibustion combined with pushpin-like needle acupuncture in the treatment of pain,nausea and vomiting after TACE:a clinical study
Xiaodi SHEN ; Pan YE ; Xuemei BIAN ; Qing SUN ; Yuru CHANG ; Yu ZHANG
Journal of Interventional Radiology 2024;33(9):1014-1018
Objective To investigate the clinical effect of air moxibustion combined with pushpin-like needle acupuncture,which is formulated based on the"suppressing wood-supporting earth"theory in the doctrine of the five elements of Traditional Chinese Medicine(TCM),in the treatment of pain,nausea and vomiting after transcatheter arterial chemoembolization(TACE).Methods A total of 160 patients with hepatocellular carcinoma,who were admitted to the First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine of China to receive initial TACE between July 2020 and June 2023,were enrolled in this study.The patients were randomly divided into 4 groups with 40 patients in each group.The patients of the control group received TACE with conventional nursing care,the patients of the pushpin-like needle group received pushpin-like needle acupuncture on the basis of the control group,the patients of the air moxibustion group received air moxibustion treatment on the basis of the control group,and the patients of the combination group received air moxibustion combined with pushpin-like needle acupuncture on the basis of the control group.The post-TACE pain degree(VAS scoring)and nausea/vomiting extent(INVR scoring)were compared between each other among the four groups.Results The differences in the VAS score and INVR score(including main effect and interaction effect)between each other among the four groups were statistically significant(all P<0.05).Statistically significant differences in the VAS score and INVR score existed between the control group and the other three groups(all P<0.05).The differences in the VAS score and INVR score between combination group and pushpin-like needle group,as well as between combination group and air moxibustion group were statistically significant(both P<0.05).Conclusion Air moxibustion combined with pushpin-like needle acupuncture can effectively and remarkably relieve post-TACE pain,nausea and vomiting,which is superior to simple use of air moxibustion or pushpin-like needle acupuncture.Therefor,the combination use of air moxibustion and pushpin-like needle acupuncture should be popularized in clinical practice.
9. Research progress and potential medical applications of anaplastic lymphoma kinase in treatment of non-small cell lung cancer
Bo CHEN ; Iian-Di KAN ; Li-Ying CHEN ; Fa-Qing YE ; Yan-Ting SUN
Chinese Pharmacological Bulletin 2024;40(3):415-420
During the treatment of non-small cell lung cancer ( NSCLC) , many patients have developed drug resistance due to the use of targeted EGFR inhibitors. The main reasons for drug resistance are EGFR site mutations and bypass activation. Activation of ALK pathway is one of the major types of bypass activation. A recent authoritative study indicates that ALK is closely related to immunotherapy. This article reviews the treatment of ALK in tumors from three aspects: the structure and physiological function of ALK, the small molecule inhibitor of ALK, the biological function of ALK and its related treatment methods for NSCLC, and prospects future directions for better application of ALK in the treatment of NSCLC.
10.Comparative study of trastuzumab modification analysis using mono/multi-epitope affinity technology with LC-QTOF-MS.
Chengyi ZUO ; Jingwei ZHOU ; Sumin BIAN ; Qing ZHANG ; Yutian LEI ; Yuan SHEN ; Zhiwei CHEN ; Peijun YE ; Leying SHI ; Mao MU ; Jia-Huan QU ; Zhengjin JIANG ; Qiqin WANG
Journal of Pharmaceutical Analysis 2024;14(11):101015-101015
Dynamic tracking analysis of monoclonal antibodies (mAbs) biotransformation in vivo is crucial, as certain modifications could inactivate the protein and reduce drug efficacy. However, a particular challenge (i.e. immune recognition deficiencies) in biotransformation studies may arise when modifications occur at the paratope recognized by the antigen. To address this limitation, a multi-epitope affinity technology utilizing the metal organic framework (MOF)@Au@peptide@aptamer composite material was proposed and developed by simultaneously immobilizing complementarity determining region (CDR) mimotope peptide (HH24) and non-CDR mimotope aptamer (CH1S-6T) onto the surface of MOF@Au nanocomposite. Comparative studies demonstrated that MOF@Au@peptide@aptamer exhibited significantly enhanced enrichment capabilities for trastuzumab variants in comparison to mono-epitope affinity technology. Moreover, the higher deamidation ratio for LC-Asn-30 and isomerization ratio for HC-Asn-55 can only be monitored by the novel bioanalytical platform based on MOF@Au@peptide@aptamer and liquid chromatography-quadrupole time of flight-mass spectrometry (LC-QTOF-MS). Therefore, multi-epitope affinity technology could effectively overcome the biases of traditional affinity materials for key sites modification analysis of mAb. Particularly, the novel bioanalytical platform can be successfully used for the tracking analysis of trastuzumab modifications in different biological fluids. Compared to the spiked phosphate buffer (PB) model, faster modification trends were monitored in the spiked serum and patients' sera due to the catalytic effect of plasma proteins and relevant proteases. Differences in peptide modification levels of trastuzumab in patients' sera were also monitored. In summary, the novel bioanalytical platform based on the multi-epitope affinity technology holds great potentials for in vivo biotransformation analysis of mAb, contributing to improved understanding and paving the way for future research and clinical applications.

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