1.Experts consensus on standard items of the cohort construction and quality control of temporomandibular joint diseases (2024)
Min HU ; Chi YANG ; Huawei LIU ; Haixia LU ; Chen YAO ; Qiufei XIE ; Yongjin CHEN ; Kaiyuan FU ; Bing FANG ; Songsong ZHU ; Qing ZHOU ; Zhiye CHEN ; Yaomin ZHU ; Qingbin ZHANG ; Ying YAN ; Xing LONG ; Zhiyong LI ; Yehua GAN ; Shibin YU ; Yuxing BAI ; Yi ZHANG ; Yanyi WANG ; Jie LEI ; Yong CHENG ; Changkui LIU ; Ye CAO ; Dongmei HE ; Ning WEN ; Shanyong ZHANG ; Minjie CHEN ; Guoliang JIAO ; Xinhua LIU ; Hua JIANG ; Yang HE ; Pei SHEN ; Haitao HUANG ; Yongfeng LI ; Jisi ZHENG ; Jing GUO ; Lisheng ZHAO ; Laiqing XU
Chinese Journal of Stomatology 2024;59(10):977-987
Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.
2.Quantitative analysis of the characteristics and influencing factors of hearing loss among workers exposed to noise in Tianjin
Shuying WANG ; Pei LI ; Ya GAO ; Yanming ZHOU ; Xing WANG ; Qiang ZENG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(5):346-349
Objective:To analyze the characteristics of high-frequency average hearing loss in both ears of noise exposed workers in Tianjin in 2020, and quantitatively analyze the influencing factors of high-frequency hearing loss in both ears of workers.Methods:In March 2023, Collect and organize basic information about noise-hazardous enterprises and personal information of workers exposed to noise. Data from the Tianjin Occupational Disease and Health Hazard Factors Information Monitoring System from January 2020 to December 2020, and analyze the impact of basic information of employees, enterprise size, regional distribution, industry category, and economic type on the high-frequency average hearing loss of workers during work. Apply logistic regression to quantitatively analyze the influencing factors of abnormal high-frequency average hearing threshold of noise exposed workers.Results:The size, economic type, industry category, and regional distribution of enterprises, as well as the gender, age, length of service of workers, have an impact on the abnormal high-frequency average hearing threshold of noise exposed workers (χ 2=733.56、3 497、27、1352.84、1197.62、2570.59、22.30、506.60, P<0.001) . Quantitative analysis using a logistic regression model showed that in the basic information of workers, noise exposed workers were male ( OR=2.500, P<0.001) and aged 30-39, 40-49, and 50-59 years ( OR=1.33, P<0.001; OR=1.68, P<0.001; OR=1.52, P< 0.001) , with a length of service of 4 to<10 years and≥10 years ( OR=1.08, P<0.001; OR=1.615, P<0.001) being the influencing factors for high-frequency hearing loss in both ears of noise exposed workers; In terms of enterprise characteristics, medium-sized, small and micro enterprises ( OR=1.12, P<0.001; OR=1.75, P<0.001; OR=2.09, P<0.001) , enterprises located in the fourth district around the city ( OR=1.268, P<0.001) , and enterprises with economic types of collective economy, other economy, private economy, Hong Kong, Macao and Taiwan investment, shareholding system, and other industry economies ( OR are all >1, P<0.001) are all factors affecting high-frequency hearing loss in noise exposed personnel. Conclusion:Noise is a common occupational hazard factor in Tianjin's enterprises, especially for workers in micro enterprises who face a high risk of hearing abnormalities. Therefore, enterprises need to strengthen the management and intervention of noise operations to prevent the occurrence of hearing loss in workers.
3.Quantitative analysis of the characteristics and influencing factors of hearing loss among workers exposed to noise in Tianjin
Shuying WANG ; Pei LI ; Ya GAO ; Yanming ZHOU ; Xing WANG ; Qiang ZENG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2024;42(5):346-349
Objective:To analyze the characteristics of high-frequency average hearing loss in both ears of noise exposed workers in Tianjin in 2020, and quantitatively analyze the influencing factors of high-frequency hearing loss in both ears of workers.Methods:In March 2023, Collect and organize basic information about noise-hazardous enterprises and personal information of workers exposed to noise. Data from the Tianjin Occupational Disease and Health Hazard Factors Information Monitoring System from January 2020 to December 2020, and analyze the impact of basic information of employees, enterprise size, regional distribution, industry category, and economic type on the high-frequency average hearing loss of workers during work. Apply logistic regression to quantitatively analyze the influencing factors of abnormal high-frequency average hearing threshold of noise exposed workers.Results:The size, economic type, industry category, and regional distribution of enterprises, as well as the gender, age, length of service of workers, have an impact on the abnormal high-frequency average hearing threshold of noise exposed workers (χ 2=733.56、3 497、27、1352.84、1197.62、2570.59、22.30、506.60, P<0.001) . Quantitative analysis using a logistic regression model showed that in the basic information of workers, noise exposed workers were male ( OR=2.500, P<0.001) and aged 30-39, 40-49, and 50-59 years ( OR=1.33, P<0.001; OR=1.68, P<0.001; OR=1.52, P< 0.001) , with a length of service of 4 to<10 years and≥10 years ( OR=1.08, P<0.001; OR=1.615, P<0.001) being the influencing factors for high-frequency hearing loss in both ears of noise exposed workers; In terms of enterprise characteristics, medium-sized, small and micro enterprises ( OR=1.12, P<0.001; OR=1.75, P<0.001; OR=2.09, P<0.001) , enterprises located in the fourth district around the city ( OR=1.268, P<0.001) , and enterprises with economic types of collective economy, other economy, private economy, Hong Kong, Macao and Taiwan investment, shareholding system, and other industry economies ( OR are all >1, P<0.001) are all factors affecting high-frequency hearing loss in noise exposed personnel. Conclusion:Noise is a common occupational hazard factor in Tianjin's enterprises, especially for workers in micro enterprises who face a high risk of hearing abnormalities. Therefore, enterprises need to strengthen the management and intervention of noise operations to prevent the occurrence of hearing loss in workers.
4. ZLY18 protects against angiotensin II-induced cardiac fibrosis via inhibiting TGF-β1/Smads pathway
Ding-Hu MA ; Pei-Qing LIU ; Zong-Tao ZHOU ; Zheng LI ; Yu-Xing ZHANG ; Jing LU ; Pei-Qing LIU
Chinese Pharmacological Bulletin 2023;39(2):229-238
Aim To explore the effect of ZLY18 on angiotensin II-induced cardiac fibrosis and the underlying mechanism. Methods Ang II was used to induce cardiac fibrosis in vitro and in vivo. Cardiac fibroblasts were divided into blank control group, model group and medicine group. The medicine group was subdivided into ZLY18(L)group, ZLY18(M)group and ZLY18(H)group. Compound ZLY18 was given 1, 2, 5 μmol·L-1 respectively. C57BL/6 mice were randomly divided into control group, model group and medicine group. The medicine group were subdivided into ZLY18(L)group, ZLY18(M)group and ZLY18(H)group. Compound ZLY18 was given 10,20 and 50 mg·kg-1 respectively. Both the model group and the medicine group were given with Ang II to induce cardiac fibrosis. The changes of protein levels were detected by Western blot and immunofluorescence. The changes of cardiac function indexes in C57BL/6 mice were detected by small animal echocardiography. The morphology, cell arrangement and collagen fibers of cardiac fibroblasts were observed by tissue section staining and other methods. Results The model of Ang II-induced myocardial fibrosis was successfully established at the cell and animal levels, and ZLY18 treatment improved the elevated fibrosis-related protein caused by Ang II and abnormal cardiac function in mice. Moreover, ZLY18 was able to inhibit the increased phosphorylation of TGF-1 and Smad3 caused by Ang II and increased Smad2/3 nuclear entry, suggesting that the antifibrotic effect of ZLY18 might be related to the activation of TGF-1/Smads signaling pathway. Conclusions ZLY18 has a protective effect on Ang II-induced cardiac fibrosis. ZLY18 may inhibit TGF-β/Smads signaling pathway activation to exert anti-fibrotic effects.
6.Association of cumulative resting heart rate exposure with rapid renal function decline: a prospective cohort study with 27,564 older adults.
Xi JIANG ; Xian SHAO ; Xing LI ; Pu-Fei BAI ; Hong-Yan LIU ; Jia-Mian CHEN ; Wei-Xi WU ; Zhuang CUI ; Fang HOU ; Chun-Lan LU ; Sai-Jun ZHOU ; Pei YU
Journal of Geriatric Cardiology 2023;20(9):673-683
OBJECTIVE:
To evaluate the prospective association between cumulative resting heart rate (cumRHR) and rapid renal function decline (RRFD) in a cohort of individuals aged 60 and older.
METHODS:
In the Tianjin Chronic Kidney Disease Cohort Study, the individuals who underwent three consecutive physical examinations between 2014 and 2017, with estimated glomerular filtration rate (eGFR) greater than 60 mL/min per 1.73 m2 and aged 60 years or older were enrolled. A total of 27,564 patients were prospectively followed up from January 1, 2017 to December 31, 2020. The 3-year cumRHR was calculated. The primary outcome was RRFD, defined as an annualized decline in eGFR of 5 mL/min per 1.73 m2 or greater. Logistic and restricted spline regression models and subgroup analysis were used to investigate the association of cumRHR with RRFD after adjusting for all confounders.
RESULTS:
During a median follow-up of 3.2 years, a total of 4,347 (15.77%) subjects developed RRFD. In fully-adjusted models, compared with the lowest quartile of cumRHR, the odds ratio (OR) for the highest was 1.44 (1.28-1.61), P < 0.001. Furthermore, each 1-standard deviation (27.97 beats/min per year) increment in cumRHR was associated with a 17% (P < 0.001) increased risk of RRFD, with a linear positive correlation (P for non-linear = 0.803). Participants with a 3-year cumRHR ≥ 207 (beats/min) * year (equivalent to ≥ 69 beats/min per year in 3 years) were found to be at a higher risk of RRFD.
CONCLUSIONS
The cumRHR is significantly associated with a higher risk of RRFD among older adults. These results might provide an effective goal for managing and delaying the decline of renal function in the older adults.
7.Danhong Injection Up-regulates miR-125b in Endothelial Exosomes and Attenuates Apoptosis in Post-Infarction Myocardium.
Si-Nai LI ; Zi-Hao LIU ; Ming-Xue ZHOU ; Wei-Hong LIU ; Xiao-Lei LAI ; Ping LI ; Lei ZHANG ; Ju-Ju SHANG ; Sheng-Lei QIU ; Yan LOU ; Yu-Pei TAN ; Wen-Long XING ; Hong-Xu LIU
Chinese journal of integrative medicine 2023;29(12):1099-1110
OBJECTIVE:
To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis.
METHODS:
A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities.
RESULTS:
DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01).
CONCLUSION
DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice
;
Animals
;
Tumor Suppressor Protein p53/metabolism*
;
Endothelial Cells/metabolism*
;
Exosomes/metabolism*
;
bcl-2-Associated X Protein/metabolism*
;
Myocardium/metabolism*
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Myocardial Infarction/drug therapy*
;
Apoptosis
;
MicroRNAs/metabolism*
8.Inhibition of glutaminolysis alleviates myocardial fibrosis induced by angiotensin II.
Pan-Pan WANG ; Hao-Miao BAI ; Si-Yu HE ; Zi-Qi XIA ; Mei-Jie LIU ; Jiong AN ; Jia-Heng ZHOU ; Chen-Han LI ; Wei ZHANG ; Xing ZHANG ; Xin-Pei WANG ; Jia LI
Acta Physiologica Sinica 2023;75(2):179-187
The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.
Rats
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Mice
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Animals
;
Rats, Sprague-Dawley
;
Angiotensin II/pharmacology*
;
Fibroblasts
;
Mice, Inbred C57BL
;
Fibrosis
;
Collagen/pharmacology*
;
Collagen Type I/metabolism*
;
RNA, Messenger/metabolism*
;
Myocardium/pathology*
9.A multicenter epidemiological study of acute bacterial meningitis in children.
Cai Yun WANG ; Hong Mei XU ; Jiao TIAN ; Si Qi HONG ; Gang LIU ; Si Xuan WANG ; Feng GAO ; Jing LIU ; Fu Rong LIU ; Hui YU ; Xia WU ; Bi Quan CHEN ; Fang Fang SHEN ; Guo ZHENG ; Jie YU ; Min SHU ; Lu LIU ; Li Jun DU ; Pei LI ; Zhi Wei XU ; Meng Quan ZHU ; Li Su HUANG ; He Yu HUANG ; Hai Bo LI ; Yuan Yuan HUANG ; Dong WANG ; Fang WU ; Song Ting BAI ; Jing Jing TANG ; Qing Wen SHAN ; Lian Cheng LAN ; Chun Hui ZHU ; Yan XIONG ; Jian Mei TIAN ; Jia Hui WU ; Jian Hua HAO ; Hui Ya ZHAO ; Ai Wei LIN ; Shuang Shuang SONG ; Dao Jiong LIN ; Qiong Hua ZHOU ; Yu Ping GUO ; Jin Zhun WU ; Xiao Qing YANG ; Xin Hua ZHANG ; Ying GUO ; Qing CAO ; Li Juan LUO ; Zhong Bin TAO ; Wen Kai YANG ; Yong Kang ZHOU ; Yuan CHEN ; Li Jie FENG ; Guo Long ZHU ; Yan Hong ZHANG ; Ping XUE ; Xiao Qin LI ; Zheng Zhen TANG ; De Hui ZHANG ; Xue Wen SU ; Zheng Hai QU ; Ying ZHANG ; Shi Yong ZHAO ; Zheng Hong QI ; Lin PANG ; Cai Ying WANG ; Hui Ling DENG ; Xing Lou LIU ; Ying Hu CHEN ; Sainan SHU
Chinese Journal of Pediatrics 2022;60(10):1045-1053
Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ2=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent
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Brain Abscess
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Child
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Child, Preschool
;
Escherichia coli
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Female
;
Humans
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Hydrocephalus
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Infant
;
Infant, Newborn
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Male
;
Meningitis, Bacterial/epidemiology*
;
Retrospective Studies
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Streptococcus agalactiae
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Streptococcus pneumoniae
;
Subdural Effusion
;
beta-Lactamases
10.Analysis of components of proteins from Echinococcus granulosus cyst fluid
Shu-Ying WANG ; Xiao-Di YANG ; Hong-Yu GAO ; Jing-Yu XING ; Qi HU ; Ting-Ting HUANG ; Pei WU ; Yi-Ting ZHAO ; Hao-Wei LIU ; Wei-Yue LIU ; Hui-Na WANG ; Rui ZHOU ; Liang CHU
Chinese Journal of Schistosomiasis Control 2021;33(5):476-482
Objective To analyze the components of proteins from Echinococcus granulosus cyst fluid using the shotgun method, and to identify the active components with potential regulatory effects for immune dysregulation diseases. Methods The E. granulosus cyst fluid was collected aseptically from the hepatic cysts of patients with cystic echinococcosis, and characterized by liquid chromatography (LC) tandem mass spectrometry (MS/MS) following digestion with trypsin. The protein data were searched using the software MaxQuant version 1.6.1.0 and the cellular components, molecular functions, and biological processes of the identified proteins were analyzed using the Gene Ontology (GO) method. Results The E. granulosus cyst fluid separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) had a relative molecular mass of 25 to 70 kDa. LS-MS/MS analysis identified 37 proteins, including 32 known proteins and 5 unknown proteins. At least 4 proteins were preliminarily found to exhibit potential regulatory effects for immune dysregulation diseases, including antigen B, glutathione-S-transferase (GST), thioredoxin peroxidase (TPX) and malate dehydrogenase (MDH). GO enrichment analysis showed that the identified proteins had 149 molecular functions and were involved in 341 biological processes. Conclusions E. granulosus cyst fluid has a variety of protein components, and four known proteins are preliminarily identified to be associated with immune dysregulation diseases.

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