1.Research progress on the mechanism of action of rosmarinic acid in the prevention of cardiovascular diseases
Ke CAI ; Sheng-ru HUANG ; Fang-fang GAO ; Xiu-juan PENG ; Sheng GUO ; Feng LIU ; Jin-ao DUAN ; Shu-lan SU
Acta Pharmaceutica Sinica 2025;60(1):12-21
With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.
2.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.
3.Efficacy and Safety of Plerixafor Combined with G-CSF for Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization in Lymphoma Patients.
Fang-Shu GUAN ; Dong-Hua HE ; Yi LI ; Yi ZHANG ; Gao-Feng ZHENG ; Yuan-Yuan ZHU ; Jing-Song HE ; En-Fan ZHANG ; Zhen CAI ; Yi ZHAO
Journal of Experimental Hematology 2023;31(4):1056-1060
OBJECTIVE:
To investigate the efficacy and safety of plerixafor combined with granulocyte colony-stimulating factor (G-CSF) in mobilizing peripheral blood hematopoietic stem cells in patients with lymphoma.
METHODS:
The clinical data of lymphoma patients who received autologous hematopoietic stem cell mobilization using plerixafor combined with G-CSF from January 2019 to December 2021 were retrospectively analyzed. The patients received 3 kinds of mobilization regimens: front-line steady-state mobilization, preemptive intervention, and recuse mobilization. The acquisition success rate, excellent rate of collection, and incidence of treatment-related adverse reaction were counted. The influence of sex, age, disease remission status, bone marrow involvement at diagnosis, chemotherapy lines, number of chemotherapy, platelet count and number of CD34+ cells on the day before acquisition in peripheral blood on the collection results were analyzed to identify the risk factors associated with poor stem cell collection.
RESULTS:
A total of 43 patients with lymphoma were enrolled, including 7 cases who received front-line steady-state mobilization, 19 cases who received preemptive intervention, and 17 cases who received recuse mobilization. The overall acquisition success rate was 58.1% (25/43) after use of plerixafor combined with G-CSF, and acquisition success rate of front-line steady-state mobilization, preemptive intervention, and recuse mobilization was 100%, 57.9%(11/19), and 41.2%(7/17), respectively. The excellent rate of collection was 18.6%(8/43). A total of 15 patients experienced mild to moderate treatment-related adverse reactions. The number of CD34+ cells < 5 cells/μl in peripheral blood on the day before collection was an independent risk factor affecting stem cell collection.
CONCLUSIONS
Plerixafor combined with G-CSF is a safe and effective mobilization regimen for patients with lymphoma. The number of CD34+ cells in peripheral blood on the day before collection is an predictable index for the evaluation of stem cell collection.
Humans
;
Antigens, CD34/metabolism*
;
Granulocyte Colony-Stimulating Factor/therapeutic use*
;
Hematopoietic Stem Cell Mobilization/methods*
;
Hematopoietic Stem Cell Transplantation
;
Heterocyclic Compounds/therapeutic use*
;
Lymphoma/drug therapy*
;
Multiple Myeloma/drug therapy*
;
Retrospective Studies
;
Transplantation, Autologous
4.Long-Term Prognosis of Different Reperfusion Strategies for ST-Segment Elevation Myocardial Infarction in Chinese County-Level Hospitals: Insight from China Acute Myocardial Infarction Registry.
Chao WU ; Qiong Yu ZHANG ; Ling LI ; Xu Xia ZHANG ; Yong Chen CAI ; Jin Gang YANG ; Hai Yan XU ; Yan Yan ZHAO ; Yang WANG ; Wei LI ; Chen JIN ; Xiao Jin GAO ; Yue Jin YANG ; Shu Bin QIAO
Biomedical and Environmental Sciences 2023;36(9):826-836
OBJECTIVE:
To evaluate the long-term prognosis of patients with ST-segment elevation myocardial infarction (STEMI) treated with different reperfusion strategies in Chinese county-level hospitals.
METHODS:
A total of 2,514 patients with STEMI from 32 hospitals participated in the China Acute Myocardial Infarction registry between January 2013 and September 2014. The success of fibrinolysis was assessed according to indirect measures of vascular recanalization. The primary outcome was 2-year mortality.
RESULTS:
Reperfusion therapy was used in 1,080 patients (42.9%): fibrinolysis ( n= 664, 61.5%) and primary percutaneous coronary intervention (PCI) ( n= 416, 38.5%). The most common reason for missing reperfusion therapy was a prehospital delay > 12 h (43%). Fibrinolysis [14.5%, hazard ratio ( HR): 0.59, 95% confidence interval ( CI) 0.44-0.80] and primary PCI (6.8%, HR= 0.32, 95% CI: 0.22-0.48) were associated with lower 2-year mortality than those with no reperfusion (28.5%). Among fibrinolysis-treated patients, 510 (76.8%) achieved successful clinical reperfusion; only 17.0% of those with failed fibrinolysis underwent rescue PCI. There was no difference in 2-year mortality between successful fibrinolysis and primary PCI (8.8% vs. 6.8%, HR = 1.53, 95% CI: 0.85-2.73). Failed fibrinolysis predicted a similar mortality (33.1%) to no reperfusion (33.1% vs. 28.5%, HR= 1.30, 95% CI: 0.93-1.81).
CONCLUSION
In Chinese county-level hospitals, only approximately 2/5 of patients with STEMI underwent reperfusion therapy, largely due to prehospital delay. Approximately 30% of patients with failed fibrinolysis and no reperfusion therapy did not survive at 2 years. Quality improvement initiativesare warranted, especially in public health education and fast referral for mechanical revascularization in cases of failed fibrinolysis.
Humans
;
ST Elevation Myocardial Infarction/therapy*
;
Percutaneous Coronary Intervention
;
East Asian People
;
Treatment Outcome
;
Myocardial Reperfusion
;
Myocardial Infarction
;
Registries
;
Hospitals
5.Investigation of the chronic respiratory symptoms and pulmonary function of adult residents in Hongtong County, Shanxi Province.
Yan Yan WANG ; Zhi Ming SHI ; Guang Yao LI ; Zhi Xia ZHANG ; Jian Feng JIN ; Mei Feng CHEN ; Cai Fang HAN ; Yu XU ; Zhan Cheng GAO ; Shu Ming GUO
Chinese Journal of Preventive Medicine 2023;57(10):1571-1580
Objective: To investigate the chronic respiratory symptoms and pulmonary function of adult residents in 3 towns of Hongtong County, Shanxi Province, and to explore their risk factors. Methods: The investigation of chronic respiratory symptoms and lung function status of adult residents in Hongdong County is based on the regional population of the entire county in Hongdong County. The project was initiated by the Science and Technology Department of Linfen City and coordinated by the Hongdong County Government. The investigation will be conducted in 3 townships in Hongdong County, Linfen City, Shanxi Province from April to November 2021: Demographic characteristics, respiratory symptoms, smoking dust exposure and other personal history were collected through questionnaires. Physical examination, routine blood tests and lung function tests were also performed on each individual. SPSS 22.0 software was used to conduct t test, χ2 test, ANOVA or Kruskal-Wallis test for statistical analysis of the collected information. Results: 10 945 subjects aged 18-102 years were included in the analysis, of whom 3 754 (34.3%) were male, 1 222 (11.2%) had a history of dust exposure, 7 164 (65.5%) had used straw and firewood as cooking fuel, and 3 296 (30.1%) had a history of smoking. Among the participants, 394 (3.6%), 339 (3.1%), and 1 543 (14.1%) had respiratory symptoms such as chronic cough, sputum, and dyspnea. Statistics showed that the population with chronic respiratory symptoms was more elderly and had a smoking history, and the incidence of chronic respiratory symptoms was higher in those who smoked more than 40 packs a year (all P<0.05). Men with a history of dust exposure were more likely to suffer from chronic cough and expectoration, while emaciation and biofuel use for more than 40 years were more likely to suffer from chronic expectoration and dyspnea (all P<0.05). The median values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC in 1 second were 2.19 L/s, 3.24 L and 69.16%, respectively. Among them, the lung function of 5 801 (53.0%) respondents was lower than the expected value. The median FEV1/FVC decreased with the increase of age. The FEV1/FVC of people over 40 years old with smoking history was lower, the dust exposure history of people with decreased lung function was more than that of people with normal lung function, and the incidence of chronic expectoration and dyspnea was higher in people with decreased lung function (all P<0.05). The absolute value and ratio of eosinophils in patients with decreased ventilation function over 60 years old were significantly higher than those with normal ventilation function, but the level of body mass index (BMI) was lower (all P<0.05). Conclusion: In Hongdong County, Shanxi Province, grassroots residents have poor medical awareness, low lung function examination rate, chronic respiratory symptoms and lung function decline are associated with more risk factors. Primary medical institutions need to formulate prevention strategies and carry out lung function detection according to the actual situation, focusing on monitoring and follow-up of high-risk groups to achieve early and timely prevention, diagnosis and treatment of chronic obstructive pulmonary disease.
Aged
;
Adult
;
Humans
;
Male
;
Middle Aged
;
Female
;
Cough/epidemiology*
;
Lung
;
Pulmonary Disease, Chronic Obstructive/epidemiology*
;
Chronic Disease
;
Lung Diseases
;
Vital Capacity
;
Dyspnea
;
Dust/analysis*
;
Forced Expiratory Volume
6.Investigation of the chronic respiratory symptoms and pulmonary function of adult residents in Hongtong County, Shanxi Province.
Yan Yan WANG ; Zhi Ming SHI ; Guang Yao LI ; Zhi Xia ZHANG ; Jian Feng JIN ; Mei Feng CHEN ; Cai Fang HAN ; Yu XU ; Zhan Cheng GAO ; Shu Ming GUO
Chinese Journal of Preventive Medicine 2023;57(10):1571-1580
Objective: To investigate the chronic respiratory symptoms and pulmonary function of adult residents in 3 towns of Hongtong County, Shanxi Province, and to explore their risk factors. Methods: The investigation of chronic respiratory symptoms and lung function status of adult residents in Hongdong County is based on the regional population of the entire county in Hongdong County. The project was initiated by the Science and Technology Department of Linfen City and coordinated by the Hongdong County Government. The investigation will be conducted in 3 townships in Hongdong County, Linfen City, Shanxi Province from April to November 2021: Demographic characteristics, respiratory symptoms, smoking dust exposure and other personal history were collected through questionnaires. Physical examination, routine blood tests and lung function tests were also performed on each individual. SPSS 22.0 software was used to conduct t test, χ2 test, ANOVA or Kruskal-Wallis test for statistical analysis of the collected information. Results: 10 945 subjects aged 18-102 years were included in the analysis, of whom 3 754 (34.3%) were male, 1 222 (11.2%) had a history of dust exposure, 7 164 (65.5%) had used straw and firewood as cooking fuel, and 3 296 (30.1%) had a history of smoking. Among the participants, 394 (3.6%), 339 (3.1%), and 1 543 (14.1%) had respiratory symptoms such as chronic cough, sputum, and dyspnea. Statistics showed that the population with chronic respiratory symptoms was more elderly and had a smoking history, and the incidence of chronic respiratory symptoms was higher in those who smoked more than 40 packs a year (all P<0.05). Men with a history of dust exposure were more likely to suffer from chronic cough and expectoration, while emaciation and biofuel use for more than 40 years were more likely to suffer from chronic expectoration and dyspnea (all P<0.05). The median values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC in 1 second were 2.19 L/s, 3.24 L and 69.16%, respectively. Among them, the lung function of 5 801 (53.0%) respondents was lower than the expected value. The median FEV1/FVC decreased with the increase of age. The FEV1/FVC of people over 40 years old with smoking history was lower, the dust exposure history of people with decreased lung function was more than that of people with normal lung function, and the incidence of chronic expectoration and dyspnea was higher in people with decreased lung function (all P<0.05). The absolute value and ratio of eosinophils in patients with decreased ventilation function over 60 years old were significantly higher than those with normal ventilation function, but the level of body mass index (BMI) was lower (all P<0.05). Conclusion: In Hongdong County, Shanxi Province, grassroots residents have poor medical awareness, low lung function examination rate, chronic respiratory symptoms and lung function decline are associated with more risk factors. Primary medical institutions need to formulate prevention strategies and carry out lung function detection according to the actual situation, focusing on monitoring and follow-up of high-risk groups to achieve early and timely prevention, diagnosis and treatment of chronic obstructive pulmonary disease.
Aged
;
Adult
;
Humans
;
Male
;
Middle Aged
;
Female
;
Cough/epidemiology*
;
Lung
;
Pulmonary Disease, Chronic Obstructive/epidemiology*
;
Chronic Disease
;
Lung Diseases
;
Vital Capacity
;
Dyspnea
;
Dust/analysis*
;
Forced Expiratory Volume
7.Relationship between TP53 mutation and prognosis and immune response in endometrial adenocarcinoma
Cui-hua CAI ; Shu ZHANG ; Ya-qi ZHANG ; Yuan GAO ; Ze-min NI
Journal of Public Health and Preventive Medicine 2022;33(5):122-127
Objective To screen the key Mutation Genes in endometrial adenocarcinoma and study the relationship between their expression and immune response and prognosis. Methods The data of 543 cases of endometrial adenocarcinoma and 177 cases of normal tissues were downloaded from the Cancer Genome Atlas (TCGA) and genotype tissue expression (GTEX) for bioinformatics analysis. 22 cases of endometrial adenocarcinoma were collected, RT-qPCR was used to verify the gene expression. Results More than 96.38% of the patients had mutations, including missense mutation, single nucleotide mutation and C>T mutation. The top 10 mutations were PTEN, PIK3CA, TTN, ARID1A, TP53, MUC16, PIK3R1, KMT2D, CTCF and CSMD3. In TCGA, the expression of TP53 mutant was significantly higher than that of wild type (P<0.0001). The expression of TP53 in cancer tissue was higher than that in normal tissue, and the expression of TP53 mutant was higher than that of wild type (P<0.05). The overall survival (OS), progression free survival (PFS), disease free survival (DFS) and disease free survival (DSS) of TP53 mutant were lower than those of TP53 wild type (P<0.0001, P<0.0001, P=0.001, P<0.0001). A total of 344 differentially expressed genes (195 up-regulated and 149 down regulated) were identified in wild-type and mutant TP53. Compared with the wild type, the mutant was negatively enriched in the “immune effector process”, “immune response”, “immune system progress”, “innate immune response” and “immune response regulation” pathways (P=0.001). The scores of T cell CD8 +, neutrophil, macrophages and meyloid dendritic cells of TP53 mutant were lower than those of wild type. Conclusion TP53 is highly expressed in endometrioid adenocarcinoma, and the expression of mutant is higher than that of wild type. TP53 mutation is positively correlated with poor prognosis and can inhibit immune response.
8.Infection status and molecular characteristics of Campylobacter isolated from diarrhea patients in Changping District of Beijing
Dong-xun LI ; Wei-jun WANG ; Hua PENG ; An-qi YIN ; Gao-lin SHU ; Heng-cai LIU
Journal of Public Health and Preventive Medicine 2022;33(6):123-127
Objective To understand the infection status and molecular characteristics of Campylobacter, and to provide evidence for the prevention and control of Campylobacter infection. Methods A total of 382 stool samples from diarrhea patients in a sentinel hospital in Changping District, Beijing, were collected in 2019. Campylobacter, Salmonella, Diarrhea Escherichia coli, and Vibrio Parahaemolyticus were detected, and the isolated Campylobacter jejuni strains were analyzed by pulsed-field gel electrophoresis (PFGE). Results The positive detection rate of Campylobacter (58 strains, 15.18%) was higher than that of Diarrhea Escherichia coli (37 strains, 9.69%), Salmonella (24 strains, 6.28%) and Vibrio Parahaemolyticus (21 strains, 5.50%), and the difference was statistically significant (χ2=26.735, P=0.000). Campylobacter strains were found in spring (14.71%), summer (18.33%), autumn (15.00%) and winter (10.00%), but there was no significant difference (χ2=2.197, P=0.533). PFGE analysis showed that 30 strains of Campylobacter jejuni had 26 PFGE patterns, and the similarity coefficient was 31.00% -100.00%. Conclusion In the study, the detection rate of Campylobacter is in the first place, and it is detected in four seasons, indicating that the infection of Campylobacter is serious in Changping District of Beijing. It is necessary to pay more attention to the infection of Campylobacter and formulate corresponding policies to prevent the outbreak caused by Campylobacter infection..
9.Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study.
Yang YANG ; Ke-Yu LU ; Rui CHENG ; Qin ZHOU ; Guang-Dong FANG ; Hong LI ; Jie SHAO ; Huai-Yan WANG ; Zheng-Ying LI ; Song-Lin LIU ; Zhen-Guang LI ; Jin-Lan CAI ; Mei XUE ; Xiao-Qing CHEN ; Zhao-Jun PAN ; Yan GAO ; Li HUANG ; Hai-Ying LI ; Lei SONG ; San-Nan WANG ; Gui-Hua SHU ; Wei WU ; Meng-Zhu YU ; Zhun XU ; Hong-Xin LI ; Yan XU ; Zhi-Dan BAO ; Xin-Ping WU ; Li YE ; Xue-Ping DONG ; Qi-Gai YIN ; Xiao-Ping YIN ; Jin-Jun ZHOU
Chinese Journal of Contemporary Pediatrics 2022;24(3):240-248
OBJECTIVES:
To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment.
METHODS:
A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group.
RESULTS:
Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05).
CONCLUSIONS
This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use*
;
Citrates
;
Humans
;
Infant
;
Infant, Newborn
;
Infant, Premature
;
Respiration, Artificial
;
Retrospective Studies
10.Genome-wide CRISPR screen identifies synthetic lethality between DOCK1 inhibition and metformin in liver cancer.
Junru FENG ; Hui LU ; Wenhao MA ; Wenjing TIAN ; Zhuan LU ; Hongying YANG ; Yongping CAI ; Pengfei CAI ; Yuchen SUN ; Zilong ZHOU ; Jiaqian FENG ; Jiazhong DENG ; Ying SHU ; Kun QU ; Weidong JIA ; Ping GAO ; Huafeng ZHANG
Protein & Cell 2022;13(11):825-841
Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals
;
Antineoplastic Agents/therapeutic use*
;
Carcinoma, Hepatocellular/metabolism*
;
Cell Line, Tumor
;
Clustered Regularly Interspaced Short Palindromic Repeats
;
Genome
;
Humans
;
Liver Neoplasms/metabolism*
;
Metformin/therapeutic use*
;
Mice
;
Phosphorylation
;
Synthetic Lethal Mutations
;
Transcription Factors/metabolism*
;
rac GTP-Binding Proteins/metabolism*


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