1.Downregulation of LINC00638 contributes to the pathogenesis of rheumatoid arthritis-associated interstitial lung disease via inhibiting the Nrf2/ARE signaling pathway
Zhuojun LIAO ; Naiwang TANG ; Jiahui CHEN ; Xueying SUN ; Jiamin LU ; Qin WU ; Ronghuan YU ; Ying ZHOU
Chinese Journal of Clinical Medicine 2025;32(3):421-431
Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n=3), RA patients without lung involvement (n=3), and healthy controls (n=3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.
2.Research progress on the mechanism of intestinal dysfunction in sepsis and intervention of traditional Chinese medicine
Yedong SHENG ; Qi LI ; Jiahao CHEN ; Zhuojun ZHANG ; Lijuan SHEN ; Shu LU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2024;31(1):106-111
Sepsis presents challenges in clinical treatment due to its high incidence,difficult treatment,and high fatality rate.The intestine has long been considered the"motor"of multiple organ dysfunction syndrome(MODS).Intestinal dysfunction is one of the common complications of sepsis,which is often neglected due to its hidden occurrence and poor clinical efficacy,leading to poor prognosis.Therefore,it is of great significance to explore the pathogenesis and treatment of intestinal dysfunction in sepsis.As an effective supplement for the clinical treatment of intestinal dysfunction in sepsis,Traditional Chinese medicine has been paid more and more attention by clinicians.This article summarizes the research progress on the pathogenesis of sepsis-induced intestinal dysfunction and the clinical application of traditional Chinese medicine(TCM),aiming to provide more ideas and references for the clinical treatment of sepsis.
3.Engineering microbial consortia through synthetic biology approach.
Jiao ZHANG ; Jiangfeng CHEN ; Yixuan CHEN ; Lei DAI ; Zhuojun DAI
Chinese Journal of Biotechnology 2023;39(5):2517-2545
There are a large number of natural microbial communities in nature. Different populations inside the consortia expand the performance boundary of a single microbial population through communication and division of labor, reducing the overall metabolic burden and increasing the environmental adaptability. Based on engineering principles, synthetic biology designs or modifies basic functional components, gene circuits, and chassis cells to purposefully reprogram the operational processes of the living cells, achieving rich and controllable biological functions. Introducing this engineering design principle to obtain structurally well-defined synthetic microbial communities can provide ideas for theoretical studies and shed light on versatile applications. This review discussed recent progresses on synthetic microbial consortia with regard to design principles, construction methods and applications, and prospected future perspectives.
Microbial Consortia/genetics*
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Synthetic Biology
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Microbiota
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Models, Theoretical
4.Establishment of a mouse model of acute systemic cold injury induced by hypothermia
Xiaoye TIAN ; Ying LIU ; Zhuojun WANG ; Zheyuan CHEN ; Feng CHENG ; Xiao HAN ; Peifang CONG ; Xiuyun SHI ; Ruiheng MA ; Hongxu JIN
Chinese Journal of Emergency Medicine 2023;32(4):521-526
Objective:To establish an animal model of acute systemic cold injury in mice.Methods:There were 98 C57BL/6 mice, half male and half female, with body weight of 22-27 g and age of 10 weeks. The mice were randomly divided into 7 groups ( n=14) according to the changes of anal temperature in cold environment, namely, group A (38.5 ± 1) ℃, group B (35 ± 1) ℃, group C (30 ± 1) ℃, group D (25 ± 1) ℃, group E (20 ± 1) ℃, group F (15 ± 1) ℃, and group G (10 ± 1) ℃, among which, group A was the blank control group, and the rest groups were the experimental group. The mice in the blank control group were placed in the normal environment (20 ± 5) ℃, and the mice in the experimental group were placed in the low temperature artificial climate box at - 20℃. The anal temperature of the mice was measured intermittently (as the core temperature), and the time required for the core temperature of the mice to drop to groups B, C, D, E, F and G was recorded. The righting reflex was used to evaluate the consciousness state, the action ability and the general state of each organ of mice were observed, and the blood routine and HE staining of each organ were detected. Results:The lower the core temperature of the experimental group, the longer the time required. The consciousness state, action ability, general state of organs, blood routine, and HE staining of organs in groups B, C, and D were basically the same as those in group A, and there was no acute systemic cold injury. Therefore, the blood routine, general observation of organs, and HE staining of organs in groups B, C, and D were no longer displayed compared with those in group A. Compared with group A, mice in group E began to suffer from disturbance of consciousness and action ability. With the decrease of core body temperature, the damage was aggravated, and mice in group G died. Compared with group A, the indices of blood routine test (WBC, RBC, HGB, PLT) of mice in group E began to decrease, and the univariate variance calculation showed that only WBC changes had statistical significance ( P<0.05). Compared with groups A and E, the indices of blood routine test (WBC, RBC, HGB, PLT) of mice in group F were further reduced, and the changes of each index in univariate variance calculation were statistically significant ( P<0.05). The general observation results showed that compared with group A, the lung, liver and spleen surfaces of mice in group E began to darken, and compared with groups A and E, the lung, liver, spleen, kidney and heart of mice in group F were further deepened and darkened, with irregular edges. HE staining results of various organs showed that compared with group A, the mice in group E began to have partial alveolar structure destruction and a small amount of inflammatory cell infiltration, the central vein of the liver was slightly congested, and the red and white pulp of the spleen were indistinct. Compared with groups A and E, the pathological structure damage of the lung, liver, spleen, kidney, heart and brain tissues of the mice in group F was further aggravated. Conclusions:Detection of consciousness state, action ability, general state of organs, blood routine and HE staining indices of organs in mice under low temperature can simulate the progress of clinical acute cold injury, and the animal model of acute systemic cold injury was successfully prepared.
5.Epidemiological characteristics of public health emergency events of varicella in China, 2006-2021
Miaomiao WANG ; Yuehua HU ; Meiying YOU ; Xinmei CHEN ; Tianqi WANG ; Xinyu LIU ; Chengdong XU ; Zhuojun JIANG ; Xudong LI ; Dapeng YIN
Chinese Journal of Epidemiology 2023;44(12):1893-1898
Objective:To understand the epidemiological characteristics of public health emergency events (PHEE) of varicella in China from 2006 to 2021 and related response performances.Methods:The data of varicella PHEE in 31 provinces of China from 2006 to 2021 were collected through the Public Health Emergency Management Information System, Microsoft Excel 2019 software and SPSS 26.0 statistical software were used to conduct descriptive epidemiological, statistical analysis on the time, area, location distribution, scale and epidemic management.Results:A total of 11 443 PHEE involving 341 048 related cases were reported from 2006 to 2021, with an annual attack rate of 1.78%-3.80% and a total attack rate of 2.33% (341 048/14 624 042). The number of PHEE and related cases of varicella decreased from 1 107 (35 349) in 2007 to 262 (6 884) in 2012 ( Z=-2.40, P<0.001), then increased year by year to 1 318 (42 649) in 2019 ( Z=2.58, P<0.001), with a significant decline since 2020. The varicella PHEE in China presents the seasonal characteristics,the peak is from April to June and from October to December, respectively. The sub-peak of varicella PHEE in eastern China generally appears 1-2 months earlier than in central and western China. Varicella PHEE reports are mainly distributed in eastern China, the attack rate is relatively high in western China, school-reported varicella PHEE was 88.26% of the total reports (10 099/11 443). The epidemic scale of varrcella PHEE typically range from 10 to 29 cases per year among the given outbreaks. The M ( Q1, Q3) of average number of cases, average duration, and average reporting interval of PHEE were 23 (16,35), 20 (14, 26) days, and 9 (5,19) days, respectively, and the reporting interval was positively correlated with the duration ( r=0.854, P<0.001). Conclusions:The varicella PHEE in China from 2006 to 2021 has not been effectively controlled. Schools are the key places to prevent and control varicella PHEE. Improving the sensitivity of varicella PHEE monitoring, strengthening the timely disposal of varicella epidemic, and promoting varicella vaccination are effective measures to prevent and control varicella PHEE.
6.Research and clinical primary application on 3D modeling and printing of fetal hearts based on ultrasound spatio-temporal image correlation imaging technology
Na HOU ; Yitong GUO ; Zekai ZHANG ; Yuntao CHEN ; Zhuojun MAO ; Jiahe LIANG ; Jiangpu YI ; Tiesheng CAO ; Lijun YUAN
Chinese Journal of Ultrasonography 2022;31(4):295-303
Objective:To explore the feasibility and accuracy of three-dimensional (3D) modeling methods based on ultrasound imaging data for normal and abnormal fetal cardiac structures, and to construct a methodology system for 3D printing of fetal heart based on ultrasound.Methods:A total of 93 fetuses examined in Tangdu Hospital of Air Force Military Medical University from January to December 2019 were selected. Fetal echocardiography was obtained using spatio-temporal image correlation (STIC). Ninety-three hearts were 3D modeled by blood flow modeling, blood pool modeling and cavity modeling, and printed by stereolithography technique. The data measured on the 3D digital models and 3D printed solid models were compared with the corresponding fetal echocardiographic images respectively in order to evaluate the accuracy of the modeling methods.Results:The fetal cardiac blood flow models based on Doppler flow image data showed the malformation and trend of small blood vessels. The fetal cardiac structure models printed based on blood pool modeling displayed the malformation of heart and large blood vessels. Models printed based on cavity modeling method accurately displayed valve and structural defects.For 83 normal fetal hearts, the long diameters of left and right ventricles measured on echocardiography [(15.3±1.9)mm, (13.2±1.9)mm] were compared with those measured on digital models [(15.1±1.9)mm, (12.9±1.9)mm] and 3D printed models[(15.1±1.9)mm, (13.0±1.9)mm], respectively, and there were no significant differences between any two groups of them ( P>0.05). Bland-Altman showed good consistency for all measurements within and between operators. Conclusions:The three modeling methods, including blood flow modeling, blood pool modeling and cavity modeling, have their own advantages in displaying different types of fetal heart malformations. Appropriate modeling methods should be selected for 3D modeling and printing to make up for the limitations of single modeling method. The consistency between measurements on 3D models and those on echocardiography is high, and the repeatability between operators is good.
7.New definition of metabolic dysfunction-associated fatty liver disease with elevated brachial-ankle pulse wave velocity and albuminuria: a prospective cohort study.
Jialu WANG ; Shanshan LIU ; Qiuyu CAO ; Shujing WU ; Jingya NIU ; Ruizhi ZHENG ; Lizhan BIE ; Zhuojun XIN ; Yuanyue ZHU ; Shuangyuan WANG ; Hong LIN ; Tiange WANG ; Min XU ; Jieli LU ; Yuhong CHEN ; Yiping XU ; Weiqing WANG ; Guang NING ; Yu XU ; Mian LI ; Yufang BI ; Zhiyun ZHAO
Frontiers of Medicine 2022;16(5):714-722
A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans
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Pulse Wave Analysis
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Albuminuria
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Ankle Brachial Index
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Non-alcoholic Fatty Liver Disease/diagnosis*
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Vascular Stiffness
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Prospective Studies
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Risk Factors
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China/epidemiology*
8.Classification of patients with gout and their clinical features
Binbin ZHOU ; Huiyong CHEN ; Zhuojun ZHANG ; Ying SUN ; Lindi JIANG ; Dongmei LIU
Chinese Journal of Rheumatology 2021;25(3):145-149
Objective:To investigate the classification of patients with gout, and further analyze their clinical features.Methods:Outpatients with gout were enrolled from January 2018 to July 2019 in Depart-ment of Rheumatology, Zhongshan Hospital. Subjects were classified into four groups according to their 24-hour urinaryexcretion and fractional excretion of urate. Clinical features of different groups were analyzed using one-way Analysis of Variance (ANOVA), Kruskal-Wallis H test, or χ2 test. Results:Finally, 378 subjects were enrolled in this cross-sectional study. Among them, 186(49.2%) were renal underexcretion type, 100(26.5%) were combined type, 57(15.1%) were renal overload type, 35(9.3%) were the normal type. Renal underexcretion type was the main subtype in any age-stratified groups. With aging, the proportion of combined type decreased, while the normal type increased. Participants in the combined type were the youngest [(42±14) years of age] with the highest estimated glomerular filtration rate [(94±18) ml·min -1·1.73 m -2], while their serum urate levels were the highest [(554±104) μmol/L]. Subjects in the normal type were the oldest [(60±15) years of age] with the lowest estimated glomerular filtration rate [(71±19) mL·min -1·1.73 m -2], however, their serum urate concentrations were the lowest [(427±118) μmol/L], The difference was statistically significant (age, F=13.98; estimated glomerular filtration rate, F=16.11; urate, F=17.14; P<0.01). Prevalence of urolithiasis were similar among the four groups ( χ2 =2.00, P>0.05). Conclusion:The renal underexcretion type is the main type of gout. Young patients are more likely to suffer from combined type with the highest serum urate levels and the best renal function.
9.Echocardiography in diagnosis of complete transposition of great arteries in fetus
Xianxiang LIU ; Ruixia TIAN ; Zhuojun WEI ; Xun CHEN ; Zhuqin LI
Chinese Journal of Medical Imaging Technology 2017;33(9):1362-1365
Objective To investigate the echocardiographic features of complete transposition of the great arteries (TGA)in fetuses.Methods Prenatal echocardiographic data of 9 fetuses diagnosed as TGA by autopsy or postnatal echocardiography during January 2010 to January 2017 were retrospectively analyzed.Results All of 9 fetuses showed normal cardiac axis and atrioventricular connection on four-chamber view.Eight of them showed the baby bird's beak sign on left ventricular outflow tract view.On left and right ventricular outflow tracts view,the two great arteries were parallel in 8 fetuses.Totally 6 fetuses showed just 2 vessels on three vessels and tracheal (3VT) view.On aortic arch view,the radian of aortic arch had increased in different degrees in 7 fetuses.There were 4 fetuses with ventricular septal defect observed by both of four-chamber and left ventricular outflow tract views.Conclusion The echocardiographic features of fetuses with TGA are characteristic in left ventricular outflow tract,left and right ventricular outflow tracts,3VT and aortic arch views,including baby bird's beak sign,2 great arteries' parallel relations,only 2 vessels on 3VT view,and increased radian of aortic arch.Of these features,baby bird's beak sign is the most common.
10.Response of left ventricular structure and function to chronic intermittent hypoxia in New Zealand white rabbits by echocardiography
Chunmei JIA ; Jianping XU ; Jian WANG ; Wu CHEN ; Chen'ai WU ; Liqing YANG ; Chun LI ; Ting ZHANG ; ZhuoJun QI
Chinese Journal of Ultrasonography 2015;(7):610-614
Objective To observe the response of left ventricular (LV)function and structure to chronic intermittent hypoxia (CIH)early stage in New Zealand white rabbits by echocardiography.Methods The New Zealand white rabbits were placed in the CIH chamber and exposed to hypoxia for 8 weeks (6 hours/day,6 days/week).The flow of nitrogen and oxygen were regulated into the customized chambers by the gas control delivery system.The fraction of inspired oxygen was changed from 21 % to 8% for 25 s of every 1 70 s.LV structure and function was assessed by echocardiography at CIH 0,1 ,2,4,6,8 weeks and histopathology was done by HE staining simultaneously.Results ①LV structural variables:compared with 0 week,LV posterior wall and interventricular septum thickness thickened at 6 week.LV end diastolic increased at 8 week (P < 0.05 ).② LV systolic function variables:compared with 0 week,LV ejection fraction increased at 2 week and 4 week,decreased at 6 week and 8 week,but it was higher than 0 week (P < 0.05).Isovolumic contraction time (IVCT)decreased at 1 week,2 week,4 week (P <0.05 ).③LV diastolic function variables:compared with 0 week,Peak velocity of early diastolic period increased at 2 week and 4 week,decreased at 6 week and 8 week with E/A>1 .Isovolumic relaxation time (IVRT)decreased at 1 week and 2 week,but increased at 8 week (P < 0.05 ).④ The myocardial pathology showed that myocardial fibers disordered slightly,cardiomyocytes swelled,nuclei increased and intracellular edema when exposed to CIH for 2 week and 4 week.Vacuolar degeneration,edema and congestion were found in intercellular substance at 6 week and 8 week.Conclusions ① LV systolic and diastolic function compensation started at CIH early stage then LV structure abnormality advent later.②IVCT and IVRT are sensitive indicators of LV systolic and diastolic function compensation.

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