1.Mechanism of Inducing Ferroptosis in Hepatocellular Carcinoma Cells by Shugan Quyu Jiedu Prescription Based on p53/SLC7A11/GPX4 Pathway
Xiaojun CAI ; Renyi YANG ; Zhibin WANG ; Yilin GONG ; Ke WANG ; Lizhu LIN ; Chong ZHONG ; Jing LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(8):74-82
ObjectiveTo investigate the effect of Shugan Quyu Jiedu prescription (SGQYJDF) on inducing ferroptosis in hepatocellular carcinoma cells based on the tumor protein 53 (p53)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway. MethodMHCC97H cells were divided into the blank serum group (10% blank serum medium), SGQYJDF-containing serum low concentration group (5% SGQYJDF-containing serum and 5% blank serum medium), SGQYJDF-containing serum medium concentration group (7.5% SGQYJDF-containing serum and 2.5% blank serum medium), SGQYJDF-containing serum high concentration group (10% SGQYJDF-containing serum medium) and sorafenib group (sorafenib concentration of 10 μmol·L-1 in 10% blank serum medium). After 24 hours of intervention, the cell survival rate was detected by cell counting kit-8 (CCK-8) assay. The cell proliferation ability was detected by 5-ethynyl-2′-deoxyuridine (EdU) staining. The intracellular ferrous ion (Fe2+) level was detected by ferrous ion fluorescent probe (FerroOrange) staining. The intracellular malondialdehyde (MDA) and glutathione (GSH) levels were detected by colorimetric assays. The ultrastructure of mitochondria was observed by transmission electron microscopy. The expression levels of ferroptosis-related proteins p53, SLC7A11 and GPX4 were detected by Western blot. ResultIn terms of cell viability, compared with the blank serum group, the SGQYJDF group showed a dose-dependent decrease in the survival rate of MHCC97H cells. Effect of the medium and high concentrations of SGQYJDF on the survival rate of MHCC97H cells were significantly decreased (P<0.01). Additionally, the results of the EdU assay showed that both the medium and high concentrations of SGQYJDF were able to inhibit the proliferation ability of MHCC97H cells (P<0.05, P<0.01). Regarding the biochemical indicators of ferroptosis, compared to the blank serum group, the medium and high concentrations of SGQYJDF were able to dose-dependently increase the intracellular Fe2+ level (P<0.01). The low, medium, and high concentrations of SGQYJDF were able to dose-dependently decrease the level of GSH in MHCC97H cells (P<0.01) and increase the level of MDA in the cells (P<0.05, P<0.01). In terms of pathway-related protein expression, compared to the blank serum group, the medium and high concentrations of SGQYJDF could significantly increase the expression of p53 (P<0.01). The low, medium, and high concentrations of SGQYJDF could significantly decrease the expression of GPX4 (P<0.01). The high concentration of SGQYJDF could decrease the expression of SLC7A11 (P<0.01). In terms of the cell morphology of ferroptosis, compared with the blank serum group, transmission electron microscopy revealed that the low concentration of SGQYJDF caused mitochondrial deformation, while the medium and high concentrations of SGQYJDF resulted in reduced mitochondrial volume, increased double-layer membrane density, and decreased mitochondrial cristae. These features were similar to those of sorafenib-induced ferroptosis. Furthermore, compared with the sorafenib group, the high concentration of SGQYJDF showed no statistically significant differences in cell survival rate, proliferation ability, Fe2+ level, MDA level, and GSH level. ConclusionThe results suggest that SGQYJDF may induce ferroptosis and inhibit proliferation in hepatocellular carcinoma MHCC97H cells by upregulating the expression of p53, suppressing the expressions of GPX4 and SLC7A11, downregulating the level of GSH, and leading to the accumulation of intracellular Fe2+ and MDA.
2.Application of PSMA PET/CT in the diagnosis and treatment of localized or locally advanced prostate cancer
Ning XU ; Zhibin KE ; Jiayin CHEN
Journal of Modern Urology 2024;29(8):667-672
Prostate-specific membrane antigen positron emission tomography/computed tomography(PSMA PET/CT)is an emerging imaging technique applied in the diagnosis and treatment of localized or locally advanced prostate cancer.It can effectively avoid unnecessary biopsies,and PSMA PET/CT-guided targeted biopsy could significantly improve the detection rate of clinically significant prostate cancer(csPCa).The technology of PSMA PET-based multi-image fusion biopsy may be the emphasis in the research of prostate cancer diagnosis in future.Compared with traditional imaging techniques,PSMA PET/CT is advantageous in detecting lymph node metastasis.It can not only be used to predict the adverse pathological features,including Gleason score,positive surgical margin,and postoperative pathological upgrading,but also to evaluate the efficacy of neoadjuvant therapy,guide radiotherapy regimen,predict biochemical recurrence and detect recurrent lesions.Currently,more large-scale prospective studies are still needed to explore the application of PSMA PET/CT for localized or locally advanced prostate cancer.
3.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.
4.Renin-angiotensin system inhibitor is associated with the reduced risk of all-cause mortality in COVID-19 among patients with/without hypertension.
Huai-Yu WANG ; Suyuan PENG ; Zhanghui YE ; Pengfei LI ; Qing LI ; Xuanyu SHI ; Rui ZENG ; Ying YAO ; Fan HE ; Junhua LI ; Liu LIU ; Shuwang GE ; Xianjun KE ; Zhibin ZHOU ; Gang XU ; Ming-Hui ZHAO ; Haibo WANG ; Luxia ZHANG ; Erdan DONG
Frontiers of Medicine 2022;16(1):102-110
Consecutively hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) in Wuhan, China were retrospectively enrolled from January 2020 to March 2020 to investigate the association between the use of renin-angiotensin system inhibitor (RAS-I) and the outcome of this disease. Associations between the use of RAS-I (angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB)), ACEI, and ARB and in-hospital mortality were analyzed using multivariate Cox proportional hazards regression models in overall and subgroup of hypertension status. A total of 2771 patients with COVID-19 were included, with moderate and severe cases accounting for 45.0% and 36.5%, respectively. A total of 195 (7.0%) patients died. RAS-I (hazard ratio (HR)= 0.499, 95% confidence interval (CI) 0.325-0.767) and ARB (HR = 0.410, 95% CI 0.240-0.700) use was associated with a reduced risk of all-cause mortality among patients with COVID-19. For patients with hypertension, RAS-I and ARB applications were also associated with a reduced risk of mortality with HR of 0.352 (95% CI 0.162-0.764) and 0.279 (95% CI 0.115-0.677), respectively. RAS-I exhibited protective effects on the survival outcome of COVID-19. ARB use was associated with a reduced risk of all-cause mortality among patients with COVID-19.
Angiotensin Receptor Antagonists/therapeutic use*
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Angiotensin-Converting Enzyme Inhibitors/therapeutic use*
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COVID-19
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Humans
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Hypertension/drug therapy*
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Renin-Angiotensin System
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Retrospective Studies
5.Application of image fusion biopsy based on PSMA PET in prostate cancer
Qi HUANG ; Zhibin KE ; Ning XU
Chinese Journal of Urology 2022;43(4):317-320
Prostate biopsy is the gold standard for diagnosis of prostate cancer. Positron emission tomography (PET) of prostate-specific membrane antigen is a new imaging technology, which has high clinical value in the detection of Clinically Significant Prostate Cancer. It also has high recognition ability for local recurrence and lymph node metastasis. Targeted prostate biopsy guided by PSMA PET can improve the detection rate of clinically significant prostate cancer, help guide the selection of prostate cancer bone biopsy lesions, plan the needle path, and improve the success rate of bone biopsy in patients with mCRPC. However, prospective randomized controlled studies are still needed to explore the feasibility of PSMA PET in targeted biopsy of prostate cancer.
6.The Autism Spectrum Disorder Cohort-the sub-cohort of China National Birth Cohort
Jiangbo DU ; Ye DING ; Lei HUANG ; Yangqian JIANG ; Qingxia MENG ; Ci SONG ; Hong LYU ; Xiaoyu LIU ; Bo XU ; Yuan LIN ; Hongxia MA ; Guangfu JIN ; Hong LI ; Xiufeng LING ; Xiaoyan KE ; Hongbing SHEN ; Zhibin HU
Chinese Journal of Epidemiology 2021;42(4):591-596
Autism spectrum disorder (ASD), a representative disease of children's neurodevelopmental disorders, brings huge pressure and financial burden to families and society. It is of great significance to explore its etiology and pathogenesis. Therefore, we established an ASD Cohort based on the existing China National Birth Cohort (CNBC), which applied parallel design to recruit and follow up families who achieved pregnancy after receiving assisted reproductive technologies (ART) and families with spontaneous conception. The main aims of this study are to compare the incidence of ASD among children born after ART with those born under spontaneous pregnancy, and to evaluate the impact of ART on the neurobehavioral development of offspring. Additionally, with a variety of clinical and behavioral related information collected during pregnancy and at early life of offspring, we are able to investigate the risk factors associated with ASD comprehensively. This article briefly introduces the objectives, contents, preliminary progress, strength and limitations, as well as further prospects of the ASD cohort study, mainly focusing on the overall design and current progress.
7.Clinicopathological features of gastric mixed adenoneuroendocrine carcinoma
LI ZHIBIN ; KE BIN ; SUN LIN ; LIU NING ; LIANG HAN
Chinese Journal of Clinical Oncology 2017;44(19):953-957
Objective:To explore the clinicopathologic characteristics of gastric mixed adenoneuroendocrine carcinoma (MANEC). Methods:From January 2011 to December 2016, the clinical and pathological data of 35 patients with gastric MANEC who were diagnosed and surgically treated in Tianjin Medical University Cancer Institute and Hospital were analyzed retrospectively. Results:The average age of the 32 men and 3 women in this study was 61.6±7.5 years. Tumor locations were as follows:17 related to gastric cardia, 9 related to gastric body, 8 related to gastric antrum, and 1 related to gastric stump. Clinical symptoms were non-specific and the diagnosis relies on post-operative pathological examination. Using the histological microscope, the affected structures were detected in neuroendocrine systems and tissue linings. Immunohistochemical staining showed that carcinoembryonic antigen (CEA) and cytokeratins 8 and 18 (CK8/18) were expressed in 32 and 33 adenocarcinoma-related cases, respectively, whereas synaptophysin (Syn) and chromogranin A (CgA) were revealed in 33 and 27 neuroendocrine-related cases, respectively. Al patients received surgical resection. A total of 17 incidents of death were reported at three years after the operation, and most of the patients were at clinical stageⅢorⅣ. Conclusion:Gastric MANEC is a rare neoplasm and is often diagnosed at its advanced stage and mainly occurs in the aged population. Neuroendocrine structures and glandular tissues are the most frequent location of such condition. Diagnosis relies on both immunohistochemical and histological examinations. Surgical resection is the most effective treatment, but the prognosis of this condition remains poor.
8.The effects of low intensity pulsed ultrasound on the proliferation and differentiation of myoblasts in vitro
Qing DUAN ; Zhong YANG ; Bin SHU ; Wanlin JIANG ; Zhibin WU ; Ke DING
Chinese Journal of Physical Medicine and Rehabilitation 2013;(4):256-260
Objective To study in vitro the effects of low-intensity pulsed ultrasound (LIPUS) on the proliferation and differentiation of cultured myoblasts,and to explore the cellular and molecular mechanisms behind any therapeutic effect of LIPUS.Methods Myoblasts were isolated from the skeletal muscles of mice and cultured in vitro.Treatment and control groups of proliferating and differentiating myoblasts were defined.The treatment groups were exposed to LIPUS at 1.5 MHz and a spatial and temporal average intensity of 30 mW/cm2,for 20 min daily,the proliferation group for 6 consecutive days and the differentiation group for 4 consecutive days.The cell proliferation kinetics of the proliferation group were analyzed using flow cytometry.The expression of myogenic regulation factor MyoD and heme oxygenase-1 (HO-1) in the proliferation group,and of myosin heavy chain (MHC) in the differentiation group were examined by immunofluorescent staining.Myoblast fusion indexes were analyzed.Results In the LIPUS treatment groups the proliferating myoblasts had a higher ratio of active cells in the G2 and S phases (19.30% ±5.14%,37.00% ±8.72%),compared with the controls (10.33% ± 1.53%,25.00% ±4.36%),and the proliferation index increased significantly.The expression of HO-1 was up-regulated,while MyoD staining was unchanged.During the induction of differentiation,the myoblasts of the treatment group fused into smaller myotubes and the myoblast fusion index (18.73% ± 6.81%) was significantly lower than that of the control group (37.52% ± 11.23%),while MHC expression did not change markedly.Conclusion LIPUS can promote myoblast proliferation while inhibiting their differentiation,but it does not affect the cells' myogenic properties.HO-1 may be involved in the regulation process.

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