1.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.
2.Recent advances in nanocarrier-based drug delivery systems in treatment of rheumatoid arthritis.
Xiao LIANG ; Ya-Lan LI ; Hao-Tian BAI ; Qing-Yu ZHANG ; Zhan XIAO ; Xin SUN ; Wu-Long WEN ; Wei-Ye ZHANG ; Jing YANG ; Rui WANG
China Journal of Chinese Materia Medica 2023;48(18):4874-4883
Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.
Humans
;
Quality of Life
;
Drug Delivery Systems
;
Arthritis, Rheumatoid/drug therapy*
;
Autoimmune Diseases/drug therapy*
;
Nanotechnology
3.Prevalence of albuminuria and its association with cardiovascular diseases in Chinese residents aged over 35 years
Runqing GU ; Congyi ZHENG ; Linfeng ZHANG ; Zuo CHEN ; Xin WANG ; Xue CAO ; Yixin TIAN ; Lu CHEN ; Haoqi ZHOU ; Chen CHEN ; Zhen HU ; Yuxin SONG ; Lan SHAO ; Ye TIAN ; Zengwu WANG
Chinese Journal of Internal Medicine 2023;62(3):290-296
Objective:To investigate the prevalence of albuminuria in Chinese residents aged >35 years and its potential association with cardiovascular disease (CVD).Methods:A total of 34 647 Chinese subjects aged ≥35 years were selected by stratified multi-stage random sampling from 2012 to 2015. Data were collected through questionnaires, physical examinations, and laboratory tests. Albuminuria was categorized into 3 types according to urinary albumin-to- creatinine ratio: normal (<30 mg/g), microalbuminuria (MAU, 30-300 mg/g), and macroalbuminuria (≥300 mg/g). Measurement data were expressed as xˉ±s, and t-tests were used for comparisons between indicators. Qualitative data were expressed as rate or constituent ratio, and the χ2 test or Kruskal-Wallis test was used to examine differences. Logistic regression was used for multivariate analyses. SAS 9.4 software was used for statistical analyses, and P<0.05 was considered statistically significant. Results:The prevalence of abnormal albuminuria was 19.1%; the prevalence was 17.2% for MAU and lower in males (13.8%) than females (20.1%, P<0.01). The risk of CVD was higher among subjects with MAU ( OR=1.23, 95% CI 1.12-1.35) and macroalbuminuria ( OR=1.86, 95% CI 1.50-2.32). When MAU was complicated by hypertension and diabetes mellitus, the CVD risk was 1.76 times higher. Conclusions:The prevalence of MAU is high among Chinese subjects aged 35 years and over. Those with MAU have higher CVD risk, especially those with hypertension and diabetes mellitus.
4.Clinical Characteristics and Risk Factors in Children with Acute Leukemia Complicated with Multiple Drug Resistant Bacterial Septicemia.
Li-Li LIU ; Jia-Hui HUANG ; Ming HUANG ; Xiang LAN ; Chuan TIAN ; Zhong-Lyu YE
Journal of Experimental Hematology 2023;31(5):1563-1568
OBJECTIVE:
To investigate the clinical characteristics and risk factors of acute leukemia complicated with multi-drug resistant bacterial septicemia in children.
METHODS:
The clinical data of children with acute leukemia complicated with septicemia admitted to the Affiliated Hospital of Guangdong Medical University from January 2013 to May 2021 were retrospectively analyzed. Their flora composition and drug resistance were also analyzed. The children were divided into multi-drug resistant bacteria (MDRB) group and non-multi-drug resistant bacteria (non-MDRB) group according to the drug sensitivity results, and the differences in clinical data between the two group were compared.
RESULTS:
A total of 108 children had drug sensitivity results, 47 cases in the MDRB group, including 26 strians of Gram-positive bacteria (G+), the most common multi-drug resistant G+ bacteria were coagulase-negative staphylococci (CoNS) and Staphylococcus aureus, and the most common multi-drug resistant Gram-negative bacteria G- bacteria were Escherichia coli and Klebsiella pneumoniae subspecies pneumoniae. Compared with non-MDRB group, children in MDRB group had higher C-reactive protein (CRP) level and mortality rate (P <0.001, P =0.009), lower initial empirical anti-infection efficiency (P <0.001), and were more likely to have septic shock (P =0.003). Logistic analysis showed that the risk factors of acute leukemia complicated with MDRB septicemia in children were previous MDRB infection (OR =6.763, 95% CI: 1.141-40.092, P =0.035), duration of agranulocytosis before infection≥7 days (OR =3.071, 95% CI: 1.139-8.282, P =0.027), and previous use of antimicrobial drugs within 90 days before infection (OR =7.675, 95% CI: 1.581-37.261, P =0.011).
CONCLUSIONS
The clinical features of acute leukemia complicated with MDRB septicemia in children include a heavy inflammatory response, significantly elevated CRP, susceptibility to secondary septic shock, low efficiency of initial empirical anti-infective therapy, and high mortality rate. Previous MDRB infection, duration of agranulocytosis before infection≥7 days, and previous use of antimicrobial drugs within 90 days before infection are risk factors of acute leukemia complicated with MDRB septicemia in children.
Humans
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Child
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Shock, Septic
;
Retrospective Studies
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Sepsis
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Risk Factors
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Bacteria
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Leukemia, Myeloid, Acute/complications*
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Acute Disease
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Escherichia coli
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Anti-Infective Agents
;
Agranulocytosis
5.Nitro-oleic acid ameliorates erectile dysfunction in a streptozotocin-induced rat model of diabetes by inhibiting oxidative stress and apoptosis and activating the NO/cGMP pathway.
Chang-Bo ZHAO ; Wei-Bo CHEN ; Wen-Zhen WANG ; Fang-Xin GONG ; Cui-Qin FAN ; Ye LI ; Tian LAN ; Wen-Jing WANG ; Ming-Zhen YUAN
Asian Journal of Andrology 2023;26(1):57-66
The major vascular complications associated with diabetes make the management of diabetic mellitus erectile dysfunction (DMED) a challenging endeavor. Notable factors contributing to DMED include oxidative stress, nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway activation, and apoptosis, while nitro-oleic acid (NO2-OA) has been shown to be beneficial in treating these aspects of this condition. We, herein, investigated the effects and possible mechanisms of NO2-OA on erectile function as assessed in a streptozotocin-induced rat model of diabetes. Our results revealed that the erectile function of DMED rats was significantly impaired compared with that of the control group. However, in response to 4 weeks of NO2-OA treatment, there was an improvement in erectile function. The expression of oxidative stress-related indicators was significantly increased and the NO/cGMP pathway was impaired in the DMED group. The expression of proapoptotic factors was increased, while that of antiapoptotic factors was decreased in the DMED group. Moreover, the cell morphology in the cavernous tissue of the DMED group also changed adversely. NO2-OA treatment significantly reversed all these changes observed in the DMED group. In conclusion, NO2-OA treatment partially improved erectile function in DMED rats through mechanisms that included inhibition of oxidative stress, activation of the NO/cGMP pathway, and a reduction in apoptosis.
6.Current status of hypertension prevalence, treatment and control rate among young and middle-aged population in China.
Xin WANG ; Hao Qi ZHOU ; Zha CHEN ; Lin Feng ZHANG ; Cong Yi ZHENG ; Ye TIAN ; Lan SHAO ; Man Lu ZHU ; Zeng Wu WANG ; Runlin GAO
Chinese Journal of Cardiology 2022;50(12):1169-1176
Objective: To estimate the prevalence, awareness, treatment and control rate of hypertension among young and middle-aged population in China. Methods: The analysis was based on the results of 2012-2015 China Hypertension Survey, which was a cross-sectional stratified multistage random sampling survey. A total of 229 593 subjects were included in the final analysis. The data including sex, age, living in urban and rural areas, prevalence of hypertension, history of stroke, family history of coronary heart disease and drinking, physical examination, heart rate were collected. Hypertension was defined as mean systolic blood pressure (SBP) ≥140 mmHg (1 mmHg=0.133 kPa), and (or) diastolic blood pressure (DBP) ≥90 mmHg, and (or) self-report a history of hypertension, and (or) use of antihypertensive medicine within 2 weeks before survey. Prehypertension was defined as SBP between 120-139 mmHg, and (or) DBP between 80-89 mmHg. Control of hypertension was considered for hypertensive individuals with SBP<140 mmHg and DBP<90 mmHg. The prevalence of prehypertension, hypertension, awareness, treatment, control rate were calculated, and the control rate among those with antihypertensive medication was also calculated. Results: The prevalence of prehypertension and hypertension was 43.8% (95%CI: 42.3%-45.4%), and 22.1% (95%CI: 20.8%-23.3%), respectively. The prevalence of prehypertension and hypertension was significantly higher among male than female across different age groups. The awareness, treatment, control rate of hypertension and control rate among treated hypertensive participants were 43.8%, 33.2%, 16.7%, and 40.2%, respectively. The prevalence was higher, and the control rate was lower among individuals with higher heart rate. Conclusion: The prevalence of prehypertension and hypertension among young and middle-aged population is high, the awareness, treatment and control rate need to be further improved in this population. The prevention and treatment of hypertension should be strengthened in the future to improve the control rate of hypertension in China.
Middle Aged
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Male
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Female
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Humans
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Antihypertensive Agents/therapeutic use*
;
Prehypertension/epidemiology*
;
Prevalence
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Cross-Sectional Studies
;
Hypertension/drug therapy*
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Blood Pressure
;
China/epidemiology*
7.Analysis of the long-term outcomes of different secondary surgeries for recurrent stress urinary incontinence after Burch colposuspension
Yang YE ; Weijie TIAN ; Yuan WANG ; Jianbin GUO ; Qianqian GAO ; Lan ZHU
Chinese Journal of Obstetrics and Gynecology 2022;57(10):753-757
Objective:To analyze the long-term outcomes of different secondary surgeries in women with recurrent stress urinary incontinence (SUI) after Burch colposuspension.Methods:Between February 2004 to February 2010, five women with recurrent SUI after Burch colposuspension in Peking Union Medical College Hospital were retrospectively followed up, and the long-term outcomes of secondary surgeries were analyzed. Subjective cures of Burch colposuspension and secondary surgeries were assessed by patients′ self-reported incontinence symptoms and patient global impression of improvement questionnaire; objective cure, improvement or failure were determined by 1-hour pad test.Results:Three women underwent tension-free vaginal tape-retropubic (TVT) as the secondary surgery, one underwent tension-free vaginal tape-obturator (TVT-O), and one underwent single-incision tension-free vaginal tape-Secur (TVT-Secur). The follow-up period of five women was (14.6±2.4) years (range: 10.8 to 16.9 years). Three women undergoing TVT secondary surgery were subjectively cured; while the other two women undergoing TVT-O or TVT-Secur were not subjectively cured, but the woman undergoing TVT-O was objectively improved.Conclusions:It is feasible for women with recurrent SUI after Burch colposuspension to receive the secondary surgery. Our limited data suggests that TVT could be considered.
8.Literature analysis of leflunomide-induced interstitial pneumonia
Jiang ZENG ; Chunjiang WANG ; Hongwen WU ; Zhijie YANG ; Tian LAN ; Chao YE
China Pharmacy 2022;33(1):79-83
OBJECTIVE To study the clinical characteristics of leflunomide-induced int erstitial pneumonia (Lef-IP),and to provide reference for its clinical diagnosis ,treatment and prevention. METHODS Lef-IP cases published in domestic and foreign journals from January 2004 to June 2021 were collected. Relevant information of patients were extracted and analyzed retrospectively, including basic characteristics ,clinical manifestations ,imaging manifestations ,laboratory examinations , histopathological examinations ,treatment and outcome. RESULTS A total of 54 Lef-IP patients from case reports of 24 publications were included ,with a median age of 61 years(9-83 years). Pulmonary symptoms appeared from 3.3 weeks to 132.9 weeks(median time of 14.5 weeks). Patients with a loading dose of leflunomide have a shorter median time to pulmonary symptoms appearing (7.5 weeks). The main clinical manifestations were dyspnea (85.2%),cough(57.4%),fever(53.7%). CT imaging examination showed 19 cases with ground-glass shadow in both lungs ,and 29 cases showed interstitial infiltration in both lungs on chest radiograph;blood gas analysis showed hypoxemia and hypocapnia ;the levels of C-reactive protein and Krebs von Den lungen- 6 (KL-6)increased;histopathological examination mainly showed interstitial pneumonia (8 cases),including 3 cases of diffuse alveolar injury ,4 cases of lymphocytes in bronchoalveolar lavage fluid ,and 1 case of noncaseating granuloma. After discontinued leflunomide and symptomatic treatment (antibiotics,hormones,colecenamine,plasma exchange ),35 patients(64.8%)recovered or improved their lung symptoms. Twelve patients (22.2%)died,and patients with fever may had a higher mortality rate (34.5%, P=0.02). CONCLUSIONS The main clinical manifestations of Lef-IP are dyspnea ,cough and fever. Loading doses of leflunomide should be avoided at the beginning of treatment. When lef-IP occurs ,leflunomide is discontinued and corresponding treatment is given,and most of the patients ’pulmonary symptoms can return to normal or be improved.
9.Reduning Injection protects flu-infected mice by inhibiting infiltration of inflammatory cells in lung and down-regulating cytokine storm.
Xiao-Lan YE ; Chen-Chen TANG ; Hui LIU ; You HU ; Tian-Nan XIANG ; Yue-Juan ZHENG
China Journal of Chinese Materia Medica 2022;47(17):4698-4706
This study aimed to explore the protective effect of Reduning Injection(RDN) on mice infected by influenza virus A/PR/8(PR8) and its immune regulatory roles during viral infection. In in vivo experiments, female C57 BL/6 mice were randomly divided into phosphate buffered saline(PBS) group, PR8-infected group, oseltamivir treatment group(OSV) and RDN treatment group. After 2 h of PR8 infection, mice in the oseltamivir group were gavaged with oseltamivir 30 mg·kg~(-1), and those in the RDN treatment group were injected intraperitoneally with RDN 1.5 mL·kg~(-1)once per day for seven consecutive days. The body weight of mice in each group was recorded at the same time every morning for 16 consecutive days. The line chart of body weight change was created to analyze the protective effect of RDN on flu-infected mice. The relative mRNA expression of different cytokines(IL-6, TNF-α, MCP-1, IL-1β, MIP-2, IP-10 and IL-10) in lung samples of flu-infected mice was detected by PCR. Flow cytometry was utilized to analyze the composition of immune cells of mouse BALF samples on day 5 after infection. Mouse macrophage cell line RAW264.7 was planted and treated by different concentrations of RDN(150, 300, 600 μg·mL~(-1)) for 24 h or 48 h, and cell proliferation was detected by CCK-8 assay. RAW264.7 cells and mouse primary peritoneal macrophages were stimulated with synthetic single stranded RNA(R837), which elicited the inflammatory response by mimicking the infection of single-stranded RNA viruses. The expression of cytokines and chemokines in the supernatants of above culture system was detected by ELISA and qPCR. On days 4, 5, 6, 7 and 15 after infection, the body weight loss of mice in the RDN treatment group was alleviated compared with that of PR8-infected mice(P<0.05). RDN treatment obviously reduced lung index and the production of IL-6, TNF-α, MCP-1 and MIP-2 in lung tissues of flu-infected mice(P<0.05). The proportions of macrophages, neutrophils and T cells in mouse BALF samples were analyzed by flow cytometry, and compared with PR8-infected mice, RDN decreased the proportion of macrophages in BALF of flu-infected mice(P<0.05), and the proportion of T cells was recovered dramatically(P<0.001). In CCK-8 assay, the concentrations of RDN(150, 300, 600 μg·mL~(-1)) failed to cause cytotoxicity to RAW264.7 cells. In addition, RDN lowered the expression of inflammatory cytokines such as IL-6, TNF-α,MCP-1, IL-1β, RANTES, and IP-10 and even anti-inflammatory cytokine IL-10 in R837-induced macrophages. RDN reduced the infiltration of inflammatory macrophages and the production of excessive inflammatory cytokines, alleviated the body weight loss of flu-infected mice. What's more, RDN restored the depletion of T cells, which might prevent secondary infection and deteriorative progression of the disease. Taken together, RDN may inhibit cytokine production and therefore down-regulate cytokine storm during the infection of influenza virus.
Animals
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Anti-Inflammatory Agents/pharmacology*
;
Body Weight
;
Chemokine CCL5/pharmacology*
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Chemokine CXCL10/pharmacology*
;
Cytokine Release Syndrome
;
Cytokines/genetics*
;
Drugs, Chinese Herbal
;
Female
;
Imiquimod/pharmacology*
;
Interleukin-10
;
Interleukin-6
;
Lung
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Mice
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Mice, Inbred C57BL
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Oseltamivir/pharmacology*
;
Phosphates/pharmacology*
;
RNA
;
RNA, Messenger
;
Sincalide/pharmacology*
;
Tumor Necrosis Factor-alpha/genetics*
;
Weight Loss
10.Design of a highly potent GLP-1R and GCGR dual-agonist for recovering hepatic fibrosis.
Nazi SONG ; Hongjiao XU ; Jiahua LIU ; Qian ZHAO ; Hui CHEN ; Zhibin YAN ; Runling YANG ; Zhiteng LUO ; Qi LIU ; Jianmei OUYANG ; Shuohan WU ; Suijia LUO ; Shuyin YE ; Runfeng LIN ; Xi SUN ; Junqiu XIE ; Tian LAN ; Zhongdao WU ; Rui WANG ; Xianxing JIANG
Acta Pharmaceutica Sinica B 2022;12(5):2443-2461
Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl4, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl4-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl4-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.

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