1.Sialyltransferase ST3GAL6 silencing reduces α2,3-sialylated glycans to regulate autophagy by decreasing HSPB8-BAG3 in the brain with hepatic encephalopathy
LI XIAOCHENG ; XIAO YAQING ; LI PENGFEI ; ZHU YAYUN ; GUO YONGHONG ; BIAN HUIJIE ; LI ZHENG
Journal of Zhejiang University. Science. B 2024;25(6):485-498,中插1-中插2
End-stage liver diseases,such as cirrhosis and liver cancer caused by hepatitis B,are often combined with hepatic encephalopathy(HE);ammonia poisoning is posited as one of its main pathogenesis mechanisms.Ammonia is closely related to autophagy,but the molecular mechanism of ammonia's regulatory effect on autophagy in HE remains unclear.Sialylation is an essential form of glycosylation.In the nervous system,abnormal sialylation affects various physiological processes,such as neural development and synapse formation.ST3 β-galactoside α2,3-sialyltransferase 6(ST3GAL6)is one of the significant glycosyltransferases responsible for adding α2,3-linked sialic acid to substrates and generating glycan structures.We found that the expression of ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after ammonia induction,and the expression levels of α2,3-sialylated glycans and autophagy-related proteins microtubule-associated protein light chain 3(LC3)and Beclin-1 were upregulated in ammonia-induced astrocytes.These findings suggest that ST3GAL6 is related to autophagy in HE.Therefore,we aimed to determine the regulatory relationship between ST3GAL6 and autophagy.We found that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way of Maackia amurensis lectin-Ⅱ(MAL-Ⅱ)and neuraminidase can inhibit autophagy.In addition,silencing the expression of ST3GAL6 can downregulate the expression of heat shock protein β8(HSPB8)and Bcl2-associated athanogene 3(BAG3).Notably,the overexpression of HSPB8 partially restored the reduced autophagy levels caused by silencing ST3GAL6 expression.Our results indicate that ST3GAL6 regulates autophagy through the HSPB8-BAG3 complex.
2.Diffusion tensor imaging in assessment of structural brain networks in patients with anti-N-methyl-D-aspartate receptor encephalitis
Junhang LIU ; Yayun XIANG ; Chun ZENG ; Hanjing LIU ; Bin YU ; Yineng ZHENG ; Yongmei LI
Chinese Journal of Radiology 2022;56(4):356-363
Objective:To explore the alteration of structural network, cognitive scores in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, as well as the relationship between cognitive impairment and changes of structural networks in patients with NMDAR encephalitis.Methods:This study was a retrospective study. A total of 39 patients with anti-NMDAR encephalitis were recruited as the autoimmune encephalitis group (AE group) from the First Affiliated Hospital of Chongqing Medical University between September 2012 to December 2019, and 32 healthy volunteers with normal results of routine head MR examinations and no history of central nervous system diseases were recruited as the health control group (HC group). There were 16 males and 23 females, aged from 13 to 66 (34±15) years, with duration of disease from 11 to 110 (31±20) days in AE group, and there were 16 males and 23 females, aged from 13 to 66 (34±15) years in HC group. All subjects underwent diffusion tensor imaging (DTI) scan and cognitive function evaluation. The brain structural networks of two groups were constructed by deterministic fiber tracking techniques, and the differences of global topological properties [clustering coefficient (C p), shortest path length (L p), local efficiency (E loc), global efficiency (E glob), normalized C p (γ), normalized L p (λ), small-worldness (σ)] and local topological properties between two groups were analyzed by the graph theory approch. The correlations between characteristics of brain structural networks and cognitive function scores were further analyzed. Results:There was no significant difference in age and gender distribution between the AE group and HC group ( P>0.05). The C p [0.005(0.004, 0.007)], γ (1.76±0.13), λ (0.51±0.03) and σ value (1.57±0.13) of AE group were decreased when compared with HC group [the values were 0.007(0.004,0.017), 2.13±0.63, 0.55±0.06 and 1.73±0.36 each] ( Z=-939.00, t=-3.58, t=-4.16, t=-2.58, P<0.05). Compared with HC group, nodal efficiencies in the left middle frontal gyrus (orbital part), left and right supplementary motor areas, left olfactory cortex, left gyrus rectus, bilateral insula, left postcentral gyrus, left paracentral lobule and right heschl gyrus were changed ( P<0.05). There were five identical hub regions which contains the left middle occipital gyrus, bilateral supplementary motor areas and precuneus in both groups. However, in the AE group, three hub regions of the left middle occipital gyrus and bilateral middle temporal gyrus were reduced, and the left precentral gyrus was increased as hub region. The nodal efficiencies of the left supplementary motor areas ( r=0.393, P=0.013), right supplementary motor areas ( r=0.384, P=0.016) and left paracentral lobule ( r=0.356, P=0.026) were positively correlated with the montreal cognitive assessment scores. Conclusion:The white matter is extensively impaired in anti-NMDAR encephalitis patients and the changes of topological properties in several brain regions are correlated with cognitive decline.
3. Analysis of 8 274 cases of new coronavirus nucleic acid detection and co-infection in Wuhan
Ming WANG ; Qing WU ; Wanzhou XU ; Bin QIAO ; Jingwei WANG ; Hongyun ZHENG ; Shupeng JIANG ; Junchi MEI ; Zegang WU ; Yayun DENG ; Fangyuan ZHOU ; Wei WU ; Yan ZHANG ; Zhihua LYU ; Jingtao HUANG ; Xiaoqian GUO ; Zhen CHEN ; Lina FENG ; Zunen XIA ; Di LI ; Tiangang LIU ; Pingan ZHANG ; Yongqing TONG ; Zhiliang XU ; Yan LI
Chinese Journal of Laboratory Medicine 2020;43(0):E016-E016
Objective:
To investigate the positive rate for 2019-nCoV tests and co-infections in Wuhan district.
Methods:
A total of 8 274 cases in Wuhan were enrolled in this cross-sectional study during January 20 to February 9, 2020, and were tested for 2019-nCoV using fluorescence quantitative PCR. Both respiratory tract samples (nasopharynx, oropharynx, sputum and alveolar lavage fluid) and non-respiratory tract samples (urine, feces, anal swabs, blood and conjunctival sac swabs) were collected. If both orf1ab and N genes are positive, they are classified as nucleic acid test positive group; if both orf1ab and N genes are negative, they are classified as negative group; if single gene target is positive, they are classified as suspicious group. Individuals were divided into male group and female group according to sex. At the same time, 316 patients were tested for 13 respiratory pathogens by multiplex PCR.
Results:
Among the 8 274 subjects, 2 745 (33.2%) were 2019-nCoV infected; 5 277 (63.8%) subjects showed negative results in the 2019-nCoV nucleic acid test; and 252 cases (3.05%) was not definitive (inconclusive result). The age of cases with COVID-19 patients and inconclusive cases was significantly higher than that of cases without 2019-nCoV infection (40 vs 56,
4.Role of Siglecs and their ligands in the establishment of immune tolerance at maternal-fetal interface
Yayun ZHENG ; Ying FENG ; Dongmei SU ; Xue ZHOU ; Fang MA
Chinese Journal of Microbiology and Immunology 2019;39(4):316-320
Embryo is regarded as a semi-allograft for carrying paternal genetic information. It can escape the attack from maternal immune system and successfully implant into the uterus, which mainly relies on the establishment of immune tolerance at the maternal-fetal interface. The maternal-fetal interface is the basis for the connection and material exchange between the mother and fetus. The mechanisms of immune re-sponses at this interface are the key to the maintenance of normal pregnancy. Immunomodulatory molecules expressed at the maternal-fetal interface are vital for immune tolerance. Studies have shown that sialicacid-binding immunoglobulin-like lectins (Siglecs) are abundantly expressed at the maternal-fetal interface and play an important role in immune regulation. Siglecs are important members of the typeⅠimmunoglobulin-like superfamily. By binding with the sialic acid residues on the side chains of glycoproteins or glycolipids, Siglecs involve in immune regulation, the activation and proliferation of immune cells and immune cell-medi-ated physiological and pathological processes. Present research on the expression of Siglecs in the maternal-fetal interface is mainly focused on Siglec-6 and Siglec-10, while other Siglecs are less studied. Siglecs, such as Siglec-6 and Siglec-10, might involve in the regulation of immune tolerance at the maternal-fetal in-terface through binding to different ligands. This article briefly reviewed the expression of Siglecs and their ligands at the maternal-fetal interface and their roles in immune tolerance.
5.Disease burden of influenza in children and current status of vaccine usage in China
Muli ZHANG ; Zhibin PENG ; Jiandong ZHENG ; Yayun TAN ; Xuan WANG ; Ying QIN ; Luzhao FENG
Chinese Journal of Applied Clinical Pediatrics 2019;34(2):91-97
The annual deaths associated with influenza is estimated to be between 290 000 and 650 000,which caused substantial burden to the society.Children have the highest incidence of influenza among all age groups,which can cause overloaded medical visits and a significant increase of hospitalization risk.The severe economic burden includes not only the direct medical costs due to outpatients and hospitalization,but also the indirect burden of school absence of children and work absence of their family members.Annual vaccination is the best measure to prevent influenza,however,influenza vaccination coverage among children in China is very low,and influenza vaccination has not yet been included in the National Immunization Program.Now,the disease burden of influenza and the vaccine usage in children in China were reviewed,and in order to provide evidence for influenza control and prevention.
6. Evaluation of the application of moving epidemic method on making influenza epidemic thresholds in the 7 climate zones in China
Yayun TAN ; Lingjia ZENG ; Ying QIN ; Jiandong ZHENG ; Zhongjie LI ; Dayan WANG ; Tao CHEN ; Luzhao FENG ; Zhibin PENG
Chinese Journal of Preventive Medicine 2019;53(10):1007-1011
Objective:
We planned to evaluate the effectiveness of moving epidemic method (MEM) in calculating influenza epidemic threshold of 7 climatic zones in China mainland.
Methods:
The positive rate of influenza virus was obtained from the National Influenza Surveillance Network System from 2010/2011 to 2017/2018. We divided the 31 provinces into 7 climatic zones according to previous literatures and applied MEM to calculate the influenza epidemic threshold of 2018/2019 influenza season for these climatic zones. Sensitivity, specificity, positive predictive value and negative predictive value were calculated to evaluate the effectiveness of MEM.
Results:
Pre-epidemic threshold (the positive rate of influenza virus) varied from 9.66% (temperate zone) to 16.36% (subtropical zone) for 2018/2019 influenza season. The gap between pre-epidemic and post-epidemic thresholds was less than 5% except for plateau zone. The sensitivity was 86.16% (95
7.Evaluation of the application of moving epidemic method on making influenza epidemic thresholds in the 7 climate zones in China
Yayun TAN ; Lingjia ZENG ; Ying QIN ; Jiandong ZHENG ; Zhongjie LI ; Dayan WANG ; Tao CHEN ; Luzhao FENG ; Zhibin PENG
Chinese Journal of Preventive Medicine 2019;53(10):1007-1011
Objective We planned to evaluate the effectiveness of moving epidemic method (MEM) in calculating influenza epidemic threshold of 7 climatic zones in China mainland. Methods The positive rate of influenza virus was obtained from the National Influenza Surveillance Network System from 2010/2011 to 2017/2018. We divided the 31 provinces into 7 climatic zones according to previous literatures and applied MEM to calculate the influenza epidemic threshold of 2018/2019 influenza season for these climatic zones. Sensitivity, specificity, positive predictive value and negative predictive value were calculated to evaluate the effectiveness of MEM. Results Pre?epidemic threshold (the positive rate of influenza virus) varied from 9.66% (temperate zone) to 16.36% (subtropical zone) for 2018/2019 influenza season. The gap between pre?epidemic and post?epidemic thresholds was less than 5% except for plateau zone. The sensitivity was 86.16% (95CI: 66.81% - 98.23%), the specificity was 94.92% (95CI:91.13%-98.41%), the positive predictive value was 89.87% (95% CI : 84.39%-94.38%), the negative predictive value was 92.96% (95%CI: 84.46%-99.17%). Conclusion Overall, moving epidemic Method performs well in calculating influenza epidemic threshold in China, much better than the previous study.
8.Evaluation of the application of moving epidemic method on making influenza epidemic thresholds in the 7 climate zones in China
Yayun TAN ; Lingjia ZENG ; Ying QIN ; Jiandong ZHENG ; Zhongjie LI ; Dayan WANG ; Tao CHEN ; Luzhao FENG ; Zhibin PENG
Chinese Journal of Preventive Medicine 2019;53(10):1007-1011
Objective We planned to evaluate the effectiveness of moving epidemic method (MEM) in calculating influenza epidemic threshold of 7 climatic zones in China mainland. Methods The positive rate of influenza virus was obtained from the National Influenza Surveillance Network System from 2010/2011 to 2017/2018. We divided the 31 provinces into 7 climatic zones according to previous literatures and applied MEM to calculate the influenza epidemic threshold of 2018/2019 influenza season for these climatic zones. Sensitivity, specificity, positive predictive value and negative predictive value were calculated to evaluate the effectiveness of MEM. Results Pre?epidemic threshold (the positive rate of influenza virus) varied from 9.66% (temperate zone) to 16.36% (subtropical zone) for 2018/2019 influenza season. The gap between pre?epidemic and post?epidemic thresholds was less than 5% except for plateau zone. The sensitivity was 86.16% (95CI: 66.81% - 98.23%), the specificity was 94.92% (95CI:91.13%-98.41%), the positive predictive value was 89.87% (95% CI : 84.39%-94.38%), the negative predictive value was 92.96% (95%CI: 84.46%-99.17%). Conclusion Overall, moving epidemic Method performs well in calculating influenza epidemic threshold in China, much better than the previous study.
9. Technical guidelines for seasonal influenza vaccination in China (2018-2019)
Luzhao FENG ; Zhibin PENG ; Dayan WANG ; Peng YANG ; Juan YANG ; Yanyang ZHANG ; Jian CHEN ; Shiqiang JIANG ; Lili XU ; Min KANG ; Tao CHEN ; Yaming ZHENG ; Jiandong ZHENG ; Ying QIN ; Mengjiao ZHAO ; Yayun TAN ; Zhongjie LI ; Zijian FENG
Chinese Journal of Preventive Medicine 2018;52(11):1101-1114
Seasonal influenza vaccination is the most effective way to prevent influenza virus infection and complications from infection. Currently, China has licensed trivalent inactivated influenza vaccine (IIV3) and quadrivalent inactivated influenza vaccine (IIV4), including split-virus influenza vaccine and subunit vaccine. Except for a few major cities, influenza vaccine is a category Ⅱ vaccine, which means influenza vaccination is voluntary, and recipients must pay for it. To strengthen the technical guidance for prevention and control of influenza and operational research on influenza vaccination in China, the National Immunization Advisory Committee (NIAC) Influenza Vaccine Technical Working Group (TWG), updated the 2014 technical guidelines and compiled the "Technical guidelines for seasonal influenza vaccination in China (2018-2019)" . The main updates in this version include: epidemiology, disease burden, types of influenza vaccines, northern hemisphere influenza vaccination composition for the 2018-2019 season, IIV3 and IIV4 immune response, durability of immunity, immunogenicity, vaccine efficacy, effectiveness, safety, cost-effectiveness and cost-benefit. The influenza vaccine TWG provided the recommendations for influenza vaccination for the 2018-2019 influenza season based on existing scientific evidence. The recommendations described in this report include the following: Points of Vaccination clinics (PoVs) should provide influenza vaccination to all persons aged 6 months and above who are willing to be vaccinated and do not have contraindications. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended, and appropriate product is available. To decrease the risk of severe infections and complications due to influenza virus infection among high risk groups, the recommendations prioritize seasonal influenza vaccination for children aged 6-59 months, adults ≥60 years of age, persons with specific chronic diseases, healthcare workers, the family members and caregivers of infants <6 months of age, and pregnant women or women who plan to become pregnant during the influenza season. Children aged 6 months through 8 years require 2 doses of influenza vaccine administered a minimum of 4 weeks apart during their first season of vaccination for optimal protection. If they were vaccinated in 2017-2018 influenza season or a prior season, 1 dose is recommended. People more than 8 years old require 1 dose of influenza vaccine. It is recommended that people receive their influenza vaccination by the end of October. Influenza vaccination should be offered as soon as the vaccination is available. For the people unable to be vaccinated before the end of October, influenza vaccination will continue to be offered for the whole season. Influenza vaccine is also recommended for use in pregnant women during any trimester. These guidelines are intended for use by staff members of the Centers for Disease Control and Prevention at all levels who work on influenza control and prevention, PoVs staff members, healthcare workers from the departments of pediatrics, internal medicine, and infectious diseases, and staff members of maternity and child care institutions at all levels.
10. Establishment of β-aminopropionitrile-induced aortic dissection model in C57Bl/6J mice
Yanxiang GAO ; Yuting LIU ; Yayun ZHANG ; Jiaojiao QIU ; Tingting ZHAO ; Chang'an YU ; Jingang ZHENG
Chinese Journal of Cardiology 2018;46(2):137-142
Objective:
To establish the mouse aorta dissection (AD) model through drinking water containing β-aminopropionitrile (BAPN).
Methods:
Forty 3-week-old C57B1/6J male mice were divided into four groups according to randomized block design: control, 0.2, 0.4 and 0.8 g·kg-1·d-1 BAPN groups (dissolving respective dose of BAPN in the drinking water,

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