1.Study on the mechanism of IL-35 in autoimmune diseases
Xu LIU ; Siyu GONG ; Zhikang TIAN ; Junfeng ZHANG
Chinese Journal of Microbiology and Immunology 2021;41(5):411-416
As an anti-inflammatory factor, Interleukin 35 (IL-35) is composed of p35 subunit and EBI3 subunit. IL-35 plays an important role in many diseases, but many mechanisms are not clear. In recent years, it has been found that IL-35 plays an important immunomodulatory role in autoimmune diseases, such as rheumatoid arthritis, inflammatory bowel disease, psoriasis, idiopathic inflammatory myopathy, systemic lupus erythematosus, multiple sclerosis, type I diabetes, pemphigus and primary biliary cirrhosis, etc. This review summarizes the research progress of the mechanism of IL-35 in the above autoimmune diseases.
2.Dexmendetomidine decreases spontaneous contraction of duodenal smooth muscle of rabbits in vitro
Suibing MIAO ; Hua CHEN ; Fang CUI ; Siyu TIAN ; Shuo GU ; Yue GUAN
Chinese Pharmacological Bulletin 2016;32(8):1101-1104
Aim To observe the influences of dexmen-detomidine on the spontaneous contraction of duodenal smooth muscle of rabbits in vitro and explore the mech-anisms.Methods The rabbits ( male or female ) were stunned and the duodenums were isolated .The sam-ples of duodenal segments were connected with tension transducer , which were then put into oxygen saturation Krebs-Henseleit ( K-H) solution .The influences of dex-mendetomidine on amplitude ( AM ) and frequency ( FR ) of duodenal smooth muscle were recorded by BL-420 F biological signal processing system .The cu-mulative dosing method was used to observe the differ-ent concentrations of dexmedetomidine on duodenal smooth muscle spontaneous contraction .Glibenclamide ( Gli) was added to K-H solution before dexmendeto-midine.In the calcium-free K-H solution, calcium chloride and rynodine were added before dexmendeto-midine.The mechanisms of dexmendetomidine were studied .Results ① Dexmendetomidine reduced the amplitude of spontaneous contraction of duodenal smooth muscle in rabbits in a dose-dependent manner ( P<0.05 or P<0.01 ) , while the frequency was not obviously influenced ( P >0.05 ) .② Gli ( P <0.05 ) partly abolished the inhibitory effects of dexmendetomi-dine on duodenal smooth muscle .③ Dexmendetomi-dine inhibited the contraction of duodenum smooth muscle induced by calcium chloride ( P <0.05 ) and rynodine ( P<0.05 ) application into calcium-free K-H solution.Conclusion Dexmendetomidine inhibits the spontaneous contraction of duodenal smooth muscle of rabbits in vitro.The mechanisms may be related to ac-tivating ATP sensitive potassium channels , inhibition of the extracellular calcium influx via cell membrane and intracellular calcium release via sarcoplasmic reticulum in duodenal smooth muscle .
3.Acute cingulate cortex infarction: a retrospective case series of 21 cases
Siyu DONG ; Mei SUN ; Yufei TIAN ; Hong CHENG
International Journal of Cerebrovascular Diseases 2022;30(7):481-488
Objective:To investigate the clinical manifestations, risk factors and outcomes of patients with acute cingulate cortex (CC) infarction.Methods:Patients with acute CC infarction admitted to the Department of Neurology, the First Affiliated Hospital of Nanjing Medical University from December 2019 to April 2022 were enrolled retrospectively. According to the location of infarction, they were divided into anterior cingulate cortex (ACC) infarction group and posterior cingulate cortex (PCC) infarction group. The clinical manifestations, stroke risk factors, imaging examination and National Institutes of Health Stroke Scale (NIHSS) score of the patients were analyzed. At one month after onset, the modified Rankin Scale was used to evaluate the short-term outcome.Results:A total of 21 patients with acute CC infarction were enrolled, including 12 males (57.14%), aged 67.14±12.36 years (range, 45-89 years). There were 16 patients (76.19%) with ACC infarction, including 13 (81.25%) unilateral CC infarction. The clinical manifestations were mainly apathy, decreased concentration, and executive dysfunction. There were 5 patients (23.81%) with PCC infarction, all with unilateral onset, mainly manifested as memory loss and visual space disorder. Among the 21 patients, 18 (85.71%) had ≥2 vascular risk factors, and 13 patients (61.90%) had ≥3 vascular risk factors, of which hypertension was most common (90.48%); 19 (90.48%) were caused by atherosclerosis, and 2 (9.52%) were caused by cardiogenic embolism. After treatment, the symptoms of both groups were improved significantly, and there was statistical difference in the NIHSS score before and after treatment ( Z=4.07, P<0.01). During the follow-up, 16 patients (76.19%) had a good outcome, 5 (23.81%) had a poor outcome and no death occurred. Conclusions:ACC and PCC infarction mainly showed different forms of cognitive impairment. If the diagnosis and treatment are timely, the overall outcome of CC infarction is good.
4.Investigation of Microglia Activation and Inflammatory Cytokine Changes in Experimental Rabbits After Spinal Cord Ischemia Reperfusion
Yunlu WANG ; Lei TIAN ; Shiyao LIU ; Zhigao MA ; Siyu HOU ; Yanwei YANG ; Huixian LI ; Mu JIN ; Xiuhua DONG ; Jiakai LU ; Weiping CHENG
Chinese Circulation Journal 2017;32(4):395-400
Objective: To observe the activation of microglia and the changing rule of inflammatory cytokine as IL-6, IL-10 and nuclear factor-κB (NF-κB) in experimental rabbits after spinal cord ischemia reperfusion (SCIR) injury in order to provide theoretical basis for post-conditioning time. Methods: Rabbit SCIR injury model was established by thoracic aorta balloon occlusion. 54 New Zealand male adult white rabbits were divided into 9 groups: Sham group (the animals received balloon implantation without occlusion), SCIR-0h group (reperfusion was conducted at 0 hour of spinal cord ischemia), SCIR-1h, -2h, -3h, -8h, -24h,-48h and -72h groups. n=6 in each group. The number of normal and apoptosis neurons, the levels of Iba-1, IL-6, IL-10 and NF-κB in spinal tissue were examined and compared among different groups respectively. Results: The number of normal neuron was decreasing with the extended reperfusion time, TUNEL-positive neuron began to increasing in SCIR-8h group and the peak was reached in SCIR-24h group. The expression of Iba-1 began to elevating in SCIR-2h group and the peak was obtained in SCIR-8h group; NF-κB began to rising in SCIR-3h group and the peak was observed in SCIR-8h group; both IL-6 and IL-10 arrived the peak in SCIR-24h group. The expressions of NF-κB, IL-6 and IL-10 were positively related to Iba-1 level. Conclusion: Microglia activation had dynamic changes in experimental SCIR rabbits and the expression levels of NF-κB, IL-6 and IL-10 were positively to microglia activation; post-conditioning time at front and back to microglia activation may reduce neuron injury.
5.Three-dimensional CT classification of fracture site and injury mechanism of axis ring
Siyu HE ; Qing WANG ; Gangzhou LI ; Gaoju WANG ; Mingsheng TAN ; Jiwei TIAN ; Yong HU ; Peng LIU ; Chao WU ; Yujian HAN ; Xia JIANG
Chinese Journal of Orthopaedics 2020;40(20):1387-1396
Objectives:To observe the anatomical location and mechanism of axis ring fractures (ARF) using 3-D CT scans, and propose a new classification for such fractures.Methods:By reviewing prospectively maintained database collecting ARF from 7 medical centers in China, 202 patients were included in this study. According to anatomical location, ARFs were classified into axis arthrosis fracture (AAF) and axis bony damage (ABD). The axis ring was divided into anterior, middle, and posterior rings, based on the border of the pars interarticularis (or pedicle) of axis. According to the features of ARF and previous study, a new classification was proposed based on the anatomical features of different fracture patterns, which was divided into three types and six subtypes (A1, A2, B1, B2, C1 and C2). The incidence of AAF and ABD and their distribution in different location of axis ring and the new classification, were observed.Results:In 202 patients with ARF, 501 anatomical structures were involved. 288 AAFs were found in 178 patients (288/501, 57%), while 213 ABDs were found in 149 patients (213/501, 43%). In anterior ring, 304 structures (304/501, 61%) were involved in injury, with 225 AAF and 79 ABD. In middle ring, 99 structures (99/501, 20%) were involved in injury, and all of them were ABD. In posterior ring, 98 structures (98/501, 19%) were involved in injury, with 63 AAF and 35 ABD. The anterior ring injuries (61%) were more common than middle (20%) or posterior ring (19%). In anterior ring, AAF (84%) were morecommon than ABD (16%); In middle ring, all the injuries were ABD; In posterior ring, AAFs (64%) were more common than ABD (36%). Type A fractures were featured with pedicle fractures and were identified in 30 patients (30/202, 15%). Type A1 fractures were bilateral pedicle fracture lines symmetrically or asymmetrically and identified in 12 (6%) patients; Type A2 fractures were pedicle fracture lineson one side and inferior articular facet injuries or lamina fractures on the otherside and identified in 18 (9%) patients. Type B fractures were featured with superior articular facet injuries or posterior wall of C2 body fractures on one side and identified in 136 patients (67%). Type B1 fractures were superior articular facet injuries or posterior wall of C2 body fractures on one side and pedicle fracture on the other side and identified in 57 (28%) patients; Type B2 fractures were superior articular facet injuries or posterior wall of C2 body fractures on one side and inferior articular facet injuries or lamina fractures on the otherside and identified in 79 (39%) patients. Type C fractures were featured with bilateral superior articular facet injuries or posterior wall of C2 body fractures and identified in 36 patients (18%). Type C1 fractures were bilateral superior articular facet injuries or posterior wall of C2 body fractures symmetrically and identified in 22 (11%) patients; Type C2 fractures were bilateral superior articular facet injuries or posterior wall of C2 body fractures asymmetrically and identified in 14 (7%) patients.Conclusion:ARF could occur in different anatomical locations, and most of these fractures were caused by hyperextension and axial load on superior articular facet on one or two sides. The new CT classification of ARF with three types and six subtypes might provide all fracture patterns, which could be useful for the choice of proper diagnosis and treatment for such fractures.
6.The temporal profile of astrocytes and Jak-STAT signal pathway after spinal ischemia and reperfusion injury in rabbits
Yunlu WANG ; Lei TIAN ; Shiyao LIU ; Zhigao MA ; Siyu HOU ; Yanwei YANG ; Huixian LI ; Mu JIN ; Xiuhua DONG ; Jiakai LU ; Weiping CHENG
Chinese Journal of Thoracic and Cardiovascular Surgery 2018;34(2):104-109
Objective To observe the evolution of astrocytes,GDNF,BDNF and Jak-STAT signal pathway after spinal cord ischemia-reperfusion injury in rabbits.Methods Spinal cord ischemia was induced by means of balloon occlusion of the infrarenal aorta for 22 minutes in 54 male New Zealand white rabbits.We assigned rabbits to 9 groups (n =6),one sham group,eight operation groups.The operation process in the sham group was the same as the operation group except the ischemia reperfusion of the spinal cord.At 0 h,1 h,2 h,3 h,8 h,24 h,48 h and 72 h after reperfusion,animals were sarcrificed and the spinal cord was removed for histologic,immunohistochemical study and western blotting.Results Normal neurons were decreased with the extension of reperfusion time.Levels of GFAP increased at 3 h and reached a peak at 48 h after reperfusion.GDNF was increased reaching two peaks after injury,the first peak was at 3 h,the second was at 72 h.BDNF level was increased and peaked at 24 h after reperfusion.The expression of p-STAT3 showed a biphasic pattern which peaked at 1h and 48 h.GFAP,GDNF,BDNF were rare and the level of p-STAT3 could be neglected in sham group.Conclusion Spinal cord ischemia-reperfusion injury could induce the activation of astrocytes,the expression of GDNF,BDNF and the activation of JakSTAT signal pathway.They showed different expression rules in this study.
7.Romidepsin (FK228) improves the survival of allogeneic skin grafts through downregulating the production of donor-specific antibody via suppressing the IRE1α-XBP1 pathway.
Yuliang GUO ; Siyu SONG ; Xiaoxiao DU ; Li TIAN ; Man ZHANG ; Hongmin ZHOU ; Zhonghua Klaus CHEN ; Sheng CHANG
Journal of Zhejiang University. Science. B 2022;23(5):392-406
Antibody-mediated rejection (AMR) is one of the major causes of graft loss after transplantation. Recently, the regulation of B cell differentiation and the prevention of donor-specific antibody (DSA) production have gained increased attention in transplant research. Herein, we established a secondary allogeneic in vivo skin transplant model to study the effects of romidepsin (FK228) on DSA. The survival of grafted skins was monitored daily. The serum levels of DSA and the number of relevant immunocytes in the recipient spleens were evaluated by flow cytometry. Then, we isolated and purified B cells from B6 mouse spleens in vitro by magnetic bead sorting. The B cells were cultured with interleukin-4 (IL-4) and anti-clusters of differentiation 40 (CD40) antibody with or without FK228 treatment. The immunoglobulin G1 (IgG1) and IgM levels in the supernatant were evaluated by enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting were conducted to determine the corresponding levels of messenger RNA (mRNA) and protein expression in cultured cells and the recipient spleens. The results showed that FK228 significantly improved the survival of allogeneic skin grafts. Moreover, FK228 inhibited DSA production in the serum along with the suppression of histone deacetylase 1 (HADC1) and HDAC2 and the upregulation of the acetylation of histones H2A and H3. It also inhibited the differentiation of B cells to plasma cells, decreased the transcription of positive regulatory domain-containing 1 (Prdm1) and X-box-binding protein 1 (Xbp1), and decreased the expression of phosphorylated inositol-requiring enzyme 1 α (p-IRE1α), XBP1, and B lymphocyte-induced maturation protein-1 (Blimp-1). In conclusion, FK228 could decrease the production of antibodies by B cells via inhibition of the IRE1α-XBP1 signaling pathway. Thus, FK228 is considered as a promising therapeutic agent for the clinical treatment of AMR.
Animals
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Depsipeptides
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Endoribonucleases
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Hematopoietic Stem Cell Transplantation
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Histone Deacetylase Inhibitors/pharmacology*
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Mice
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Protein Serine-Threonine Kinases
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Skin Transplantation
8.Clustering analysis of risk factors in high-incidence areas of esophageal cancer in Yanting county
Ruiwu LUO ; Heng HUANG ; Hao CHENG ; Siyu NI ; Siyi FU ; Qinchun QIAN ; Junjie YANG ; Xinlong CHEN ; Hanyu HUANG ; Zhengdong ZONG ; Yujuan ZHAO ; Yuhe QIN ; Chengcheng HE ; Ye WU ; Hongying WEN ; Dong TIAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(03):385-391
Objective To investigate the dietary patterns of rural residents in the high-incidence areas of esophageal cancer (EC), and to explore the clustering and influencing factors of risk factors associated with high-incidence characteristics. Methods A special structured questionnaire was applied to conduct a face-to-face survey on the dietary patterns of rural residents in Yanting county of Sichuan Province from July to August 2021. Univariate and multivariate logistic regression models were used to analyze the influencing factors of risk factor clustering for EC. Results There were 838 valid questionnaires in this study. A total of 90.8% of rural residents used clean water such as tap water. In the past one year, the people who ate fruits and vegetables, soybean products, onions and garlic in high frequency accounted for 69.5%, 32.8% and 74.5%, respectively; the people who ate kimchi, pickled vegetables, sauerkraut, barbecue, hot food and mildew food in low frequency accounted for 59.2%, 79.6%, 68.2%, 90.3%, 80.9% and 90.3%, respectively. The clustering of risk factors for EC was found in 73.3% of residents, and the aggregation of two risk factors was the most common mode (28.2%), among which tumor history and preserved food was the main clustering pattern (4.6%). The logistic regression model revealed that the gender, age, marital status and occupation were independent influencing factors for the risk factors clustering of EC (P<0.05). Conclusion A majority of rural residents in high-incidence areas of EC in Yanting county have good eating habits, but the clustering of some risk factors is still at a high level. Gender, age, marital status, and occupation are influencing factors of the risk factors clustering of EC.