1.Ablation of macrophage transcriptional factor FoxO1 protects against ischemia-reperfusion injury-induced acute kidney injury.
Yao HE ; Xue YANG ; Chenyu ZHANG ; Min DENG ; Bin TU ; Qian LIU ; Jiaying CAI ; Ying ZHANG ; Li SU ; Zhiwen YANG ; Hongfeng XU ; Zhongyuan ZHENG ; Qun MA ; Xi WANG ; Xuejun LI ; Linlin LI ; Long ZHANG ; Yongzhuo HUANG ; Lu TIE
Acta Pharmaceutica Sinica B 2025;15(6):3107-3124
Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.
2.Course of disease and related epidemiological parameters of COVID-19: a prospective study based on contact tracing cohort.
Yan ZHOU ; Wen Jia LIANG ; Zi Hui CHEN ; Tao LIU ; Tie SONG ; Shao Wei CHEN ; Ping WANG ; Jia Ling LI ; Yun Hua LAN ; Ming Ji CHENG ; Jin Xu HUANG ; Ji Wei NIU ; Jian Peng XIAO ; Jian Xiong HU ; Li Feng LIN ; Qiong HUANG ; Ai Ping DENG ; Xiao Hua TAN ; Min KANG ; Gui Min CHEN ; Mo Ran DONG ; Hao Jie ZHONG ; Wen Jun MA
Chinese Journal of Preventive Medicine 2022;56(4):474-478
Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19
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Cohort Studies
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Contact Tracing
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Humans
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Incidence
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Prospective Studies
3.Anti-tumor and Phenotypic Regulation Effect of Matrine on Dendritic Cells through Regulating TLRs Pathway.
Jing-Kang WANG ; Bao-Sheng ZHAO ; Min WANG ; Chen-Yue LIU ; Ya-Qi LI ; Quan-Tao MA ; Peng-Fei LI ; Tie-Shan WANG ; Chun-Guo WANG ; Yong-Ming ZHOU
Chinese journal of integrative medicine 2021;27(7):520-526
OBJECTIVE:
To investigate the effects of matrine on antigen presentation of dendritic cells (DCs), and to explore the pharmacological mechanism of matrine on anti-tumor effect.
METHODS:
Different concentrations (0, 1, 2, 4, 8 and 16 µ g/mL) of matrine were co-cultured with DCs, the harvested DCs were co-cultured with antigens of Lewis lung cancer (LLC) cells, and then DCs and T cells were co-cultured to produce DCs-activated killer (DAK) cells, which have significant tumor-killing activity. The expression of cytokines, mRNA and protein of toll-like receptors (TLRs) in DCs were detected by enzyme linked immunosobent assay, polymerase chain reaction and Western blot, respectively. And the killing effect of DAK were measured by MTT assay.
RESULTS:
Matrine significantly increased the mRNA expression of TLR7, TLR8, myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF-6) and I κ B kinase (IKK), as well as the protein expression of TLR7 and TLR8, and up-regulated the levels of interleukin-12 (IL-12), IL-6 and tumor necrosis factor-α (TNF-α), meanwhile, it also increased the expressions of MHC-II, CD54, CD80 and CD86 in DCs. DCs-activated effector T cells had significant tumor-killing activity. When the concentration of matrine was more than 4 µg/mL, all indices had significant difference (P<0.01 or P<0.05).
CONCLUSION
Matrine plays an anti-tumor role by regulating TLRs signal transduction pathway, promoting the secretion of inflammatory cytokines and enhancing immune function.
4. Comparison of two epidemic patterns of COVID-19 and evaluation of prevention and control effectiveness: an analysis based on Guangzhou and Wenzhou
Guanhao HE ; Zuhua RONG ; Jianxiong HU ; Tao LIU ; Jianpeng XIAO ; Lingchuan GUO ; Weilin ZENG ; Zhihua ZHU ; Dexin GONG ; Lihua YIN ; Donghua WAN ; Junle WU ; Min KANG ; Tie SONG ; Jianfeng HE ; Wenjun MA
Chinese Journal of Epidemiology 2020;41(0):E035-E035
Objective To compare the epidemiological characteristics of COVID-19 in Guangzhou and Wenzhou, and evaluate the effectiveness of their prevention and control measures. Methods Data of COVID-19 cases reported in Guangzhou and Wenzhou as of 29 February, 2020 were collected. The incidence curves of COVID-19 in two cities were constructed. The real time reproduction number ( R t ) of COVID-19 in two cities was calculated respectively. Results A total of 346 and 465 confirmed COVID-19 cases were analysed in Guangzhou and Wenzhou, respectively. In two cities, most cases were aged 30-59 years (Guangzhou: 54.9%; Wenzhou: 70.3%). The incidence curve peaked on 27 January, 2020 in Guangzhou and on 26 January, 2020 in Wenzhou, then began to decline in both cities. The peaks of imported COVID-19 cases from Hubei occurred earlier than the peak of COVID-19 incidences in two cities, and the peak of imported cases from Hubei occurred earlier in Wenzhou than in Guangzhou. In early epidemic phase, imported cases were predominant in both cities, then the number of local cases increased and gradually took the dominance in Wenzhou. In Guangzhou, the imported cases was still predominant. Despite the different epidemic pattern, the R t and the number of COVID-19 cases declined after strict prevention and control measures were taken in Guangzhou and in Wenzhou. Conclusion The time and scale specific differences of imported COVID-19 resulted in different epidemic patterns in two cities, but the spread of the disease were effectively controlled after taking strict prevention and control measures.
5. Risk assessment and early warning of imported COVID-19 in 21 cities, Guangdong province
Jianxiong HU ; Tao LIU ; Jianpeng XIAO ; Guanhao HE ; Zuhua RONG ; Lihua YIN ; Donghua WAN ; Weilin ZENG ; Dexin GONG ; Lingchuan GUO ; Zhihua ZHU ; Lilian ZENG ; Min KANG ; Tie SONG ; Haojie ZHONG ; Jianfeng HE ; Limei SUN ; Yan LI ; Wenjun MA
Chinese Journal of Epidemiology 2020;41(5):658-662
Objective To assess the imported risk of COVID-19 in Guangdong province and its cities, and conduct early warning. Methods Data of reported COVID-19 cases and Baidu Migration Index of 21 cities in Guangdong province and other provinces of China as of February 25, 2020 were collected. The imported risk index of each city in Guangdong province were calculated, and then correlation analysis was performed between reported cases and the imported risk index to identify lag time. Finally, we classified the early warming levels of epidemic by imported risk index. Results A total of 1 347 confirmed cases were reported in Guangdong province, and 90.0% of the cases were clustered in the Pearl River Delta region. The average daily imported risk index of Guangdong was 44.03. Among the imported risk sources of each city, the highest risk of almost all cities came from Hubei province, except for Zhanjiang from Hainan province. In addition, the neighboring provinces of Guangdong province also had a greater impact. The correlation between the imported risk index with a lag of 4 days and the daily reported cases was the strongest (correlation coefficient: 0.73). The early warning base on cumulative 4-day risk of each city showed that Dongguan, Shenzhen, Zhongshan, Guangzhou, Foshan and Huizhou have high imported risks in the next 4 days, with imported risk indexes of 38.85, 21.59, 11.67, 11.25, 6.19 and 5.92, and the highest risk still comes from Hubei province. Conclusions Cities with a large number of migrants in Guangdong province have a higher risk of import. Hubei province and neighboring provinces in Guangdong province are the main source of the imported risk. Each city must strengthen the health management of migrants in high-risk provinces and reduce the imported risk of Guangdong province.
6.Effect of Anshen Navel Plaster on Spontaneous Activities And Levels of GABA, 5-HT in Insomnia Rats Caused by PCPA
Fuying JIAO ; Guoxin LI ; Jin MA ; Zhaoqing MU ; Yu GAN ; Min QIAO ; Tie QIAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(12):2012-2016
This experiment was aimed to mainly observe the effect of Anshen navel plaster on autonomic activities and to compare neurotransmitter gamma-aminobutyric acid (GABA) and monoamine neurotransmitter (5-HT) contents change of insomnia rats.The rats were treated by P-chlorophenylalanine (PCPA),which can make healthy rats lose sleep.The rat model of insomnia was prepared by intraperitoneal injection of PCPA.The healthy SD rats were randomly divided into the blank control group,model control group,low dosage of Anshen navel plaster group,high dosage of Anshen navel plaster group and Tongren Anshen pill group according to the random number table.EthoVision were used to record the rat's autonomic activities.Content changes of 5-HT and GABA of rats in each group were measured by enzyme-linked immunosorbent assay (ELISA).The results showed that rat's autonomic activities were decreased in the Anshen navel plaster group and Tongren Anshen pill group,which indicated that the Anshen navel plaster had a good sedative effect.Intraperitoneal injection of PCPA can remarkably change rat's serum neurotransmitter expression levels,especially GABA and 5-HT.After the intervention of experimental drugs,compared with the model group,the expression levels of GABA and 5-HT were increased significantly.It was concluded that Anshen navel plaster has obvious sedative effect.It can regulate the contents of sleep factors such as GABA and 5-HT.
7.The effects of closure to live poultry markets on Avian influenza A (H7N9) epidemics in China
Tao LIU ; Guanghu ZHU ; Bing ZHANG ; Tie SONG ; Min KANG ; Jing LU ; Yongqian ZHAO ; Zhao HUANG ; Yulin HUANG ; Xiaojie WANG ; Xinyi YANG ; Wenjun MA
Chinese Journal of Epidemiology 2017;38(12):1716-1718
Since March 2013,China had experienced five seasonal epidemics related to Avian influenza A (H7N9).An unprecedented outbreak of H7N9 epidemic started from September 2016,with 730 cases reported till June 30th 2017,in mainland China that caused profound influences on both social development and health of the people.As an emerging infectious disease,information on pathogenic characteristics,transmission patterns and other epidemiological features of H7N9 virus somehow remained unclear.Data from previous studies suggested that the live poultry market (LPM) seemed to have served as main places where H7N9 virus got originated,mutated,spread and thus infected the human beings.Hence,closure of LPMs was suggested a major measure to control and prevent H7N9 epidemics in China.However,the effectiveness of different ways of LPM closures on H7N9 epidemics had been controversial.This study systemically summarized the effects of different ways of LPM closures on H7N epidemics from previous studies,aiming to provide references for developing a better program on H7N9 control and prevention in the country.
8.Effects of ischemic postconditioning on pneumocyte apoptosis after lung ischemia/reperfusion injury in rats.
Lu SHI ; Xu-Guang JIA ; Min LUO ; Ya-Kun LIU ; Shan ZHAO ; Hai-E CHEN ; Ying-Chun MA ; Dan CHEN ; Wan-Tie WANG
Chinese Journal of Applied Physiology 2014;30(1):60-63
OBJECTIVETo investigate the effects of ischemic postconditioning (IPostC) on pneumocyte apoptosis after lung ischemia/reperfusion injury in rats.
METHODSAdult male SD rats were randomly divided into 3 groups based upon the intervention (n = 8): control group (C), lung ischemic reperfusion group (LIR), LIR+ IPostC group (IPostC). At the end of the experiment, blood specimens drawn from the arteria carotis were tested for the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and myeloperoxidase (MPO); the pneumocyte apoptosis index (AI) was achieved by tennrminal deoxynucleotidyl transferase mediated dUTP nick end abeling (TUNEL); the expression of Bcl-2, Bax protein in lung tissue was accessed by quantitative immunohistochemistry (MHC) and Bcl-2, Bax mRNA by RT-PCR.
RESULTSIPostC could significantly attenuate the MDA level, MPO activity and improve SOD activity in blood serum which was comparable to I/R and significantly reduced the number of TUNEL-positive cells compared with I/R group, expressed as Al (% total nuclei) from (39.0 +/- 3.46) to (8.0 +/- 0.88) (P < 0.01). The protein and mRNA expression of Bcl-2 and Bax showed that IPO significantly attenuated the ischemia/reperfusion-upregulated expression of Bax protein but improved the expression of Bcl-2 that improved the Bcl-2/Bax ratio (P < 0.01) .
CONCLUSIONIPostC may attenuate pneumocyte apoptosis in LIRI by up-regulating expression of Bcl-2/Bax ratio and by inhibiting oxidant generation and neutrophils filtration.
Alveolar Epithelial Cells ; cytology ; Animals ; Apoptosis ; Ischemic Postconditioning ; Lung ; metabolism ; pathology ; Lung Injury ; physiopathology ; Male ; Malondialdehyde ; metabolism ; Peroxidase ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; physiopathology ; Superoxide Dismutase ; metabolism ; bcl-2-Associated X Protein ; metabolism
9.Comparison of the relativity of MRI appearance of cartilage injuries and postoperative effect of arthroscope on articular cartilage disease of knee.
Guang YANG ; Shi-gui YAN ; Jian-jv FENG ; Ye-jun WANG ; Jian-ping ZHONG ; Tie-min LIU ; Yun-miao MA ; Zhi-yang GAO ; Tie-feng XU
China Journal of Orthopaedics and Traumatology 2010;23(2):90-93
OBJECTIVETo analyze the indication of arthroscope by examining the correlations between cartilage injury degree confirmed by MRI and postoperative effect.
METHODSFrom Aug. 2005 to April 2008, 87 cases with knee osteoarthritis were treated by arthroscopes including 44 males and 43 females,aged from 16 to 67 years (means 46.3 years). Arthrodial cartilage of knee was graded by ICRS MR, and the therapeutic effect was evaluated by Lysholm scoring.
RESULTSAll 87 knees of 87 cases were followed-up for from 12 to 30 months (averaged 23 months). The cartilage injury degree of knees was graded as follows: grade 4 in 30 cases, grade 3 in 23 cases, grade 2 in 20 cases, grade 1 in 12 cases, grade 0 in 2 cases, means grade (2.770 +/- 1.138). Postoperative Lysholm score was from 59 to 100, means (95.170 +/- 7.556). Coefficient correlation (r) = -0.152, P = 0.159 > 0.05. Although the results had no correlations between cartilage injury degree and Lysholm score, negative correlation tendency existed.
CONCLUSIONThe patients with higher grade of knee cartilage injury degree confirmed by MRI (1.5T) have worse effect after operation, the grade is not a gold standard as a operation indication in arthroscopic procedure.
Adolescent ; Adult ; Aged ; Arthroscopy ; Cartilage, Articular ; pathology ; Female ; Humans ; Knee Joint ; pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Osteoarthritis, Knee ; pathology ; surgery
10.Study on the correlation between knee osteoarthritis imaging and effects of arthroscope.
Guang YANG ; Shi-Gui YAN ; Jian-Ju FENG ; Ye-Jun WANG ; Jian-Ping ZHONG ; Tie-Min LIU ; Yun-Miao MA ; Zhi-Yang GAO ; Tie-Feng XU
China Journal of Orthopaedics and Traumatology 2010;23(12):899-902
OBJECTIVETo explore the indications of arthroscope for the treatment of knee osteoarthritis and investigate the correlation between knee osteoarthritis imaging and effects of arthroscope.
METHODSFrom 2005.8 to 2008.4, 86 patients with knee osteoarthritis underwent arthroscope examination and treatment. Among the patients, 44 patients were male, and 42 patients were female, ranging in age from 46 to 67 years, averaged 56.3 years. Arthrodial cartilage of knee was graded by ICRS MR, and by Kellgern Laqrence X-ray. All the patients were followed up, and the duration ranged from 12 to 30 months. The Lysholm score was evaluated at the follow-up time.
RESULTSAmong 86 knees in 86 cases, cartilage injury degree of knees was graded as follows: grade 4 in 30 cases, grade 3 in 22 cases, grade 2 in 20 cases, grade 1 in 12 cases, grade 0 in 2 cases, mean grade (2.77 +/- 1.138). Postoperative Lysholm score ranged from 59 to 100, averaged (95.17 +/- 7.556), Kendall's correlation coefficient was -0.089, P = 0.317. There was no correlations between cartilage injury degree and Lysholm score. X-ray of knees was graded as follows: grade 4 in 0 cases, grade 3 in 24 cases, grade 2 in 38 cases, grade 1 in 17 cases, grade 0 in 7 cases, mean grade was (2.13 +/- 0.67), the Kendall's correlation coefficient was -0.851 with negative correlations (P = 0.036) between postoperative Lysholm score and K/L grade.
CONCLUSIONThere is no correlation between the grade of knee cartilage injury confirmed by MRI (1.5T) and effects of arthroscopy, and the grade is not a gold standard as an operation indication in arthroscope procedure. The K/L grade in X-ray had important effects.
Aged ; Arthroscopes ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Osteoarthritis, Knee ; diagnostic imaging ; pathology ; Radiography

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