1.OX40 ligand promotes follicular helper T cell differentiation and development in mice with immune thrombocytopenia.
Ziyin YANG ; Lei HAI ; Xiaoyu CHEN ; Siwen WU ; Yan LV ; Dawei CUI ; Jue XIE
Journal of Zhejiang University. Science. B 2025;26(3):240-253
Immune thrombocytopenia (ITP) is a hemorrhagic autoimmune disease characterized by antibody-mediated platelet injury. ITP has complicated immunopathological mechanisms that need further elucidation. It is well known that the costimulatory molecules OX40 ligand (OX40L) and OX40 play essential roles in the immunological mechanisms of autoimmune diseases. Previously, we discovered that the expression of OX40L and OX40 is significantly increased in the peripheral blood mononuclear cells (PBMCs) of ITP patients. In our present study, OX40L-induced follicular helper T (Tfh) cells exhibited an activated phenotype with elevated expression of inducible T-cell costimulator (ICOS), programmed cell death protein-1 (PD-1), and cluster of differentiation 40 ligand (CD40L) in vitro. Moreover, aberrant OX40L‒OX40 expression might promote the Tfh1-to-Tfh2 shift in vivo, inducing the generation of autoantibodies by enhancing the helper function of Tfh cells for B lymphocytes in a mouse model, which might accelerate the progression of ITP. Additionally, signal transduction through the OX40L‒OX40 axis might be related to the activation of tumor necrosis factor receptor-associated factor (TRAF)‒nuclear factor-κB (NF-κB) and Janus kinase (JAK)‒signal transducer and activator of transcription (STAT) signaling pathways. Overall, OX40L‒OX40 signaling is proposed as a potential novel therapeutic target for ITP.
Animals
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OX40 Ligand/physiology*
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Purpura, Thrombocytopenic, Idiopathic/immunology*
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Cell Differentiation
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Mice
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T-Lymphocytes, Helper-Inducer/cytology*
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T Follicular Helper Cells/cytology*
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Signal Transduction
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Receptors, OX40
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Mice, Inbred C57BL
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Humans
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Female
2.GLP-1RAs attenuated obesity and reversed leptin resistance partly via activating the microbiome-derived inosine/A2A pathway.
Chunyan DONG ; Bailing ZHOU ; Binyan ZHAO ; Ke LIN ; Yaomei TIAN ; Rui ZHANG ; Daoyuan XIE ; Siwen WU ; Li YANG
Acta Pharmaceutica Sinica B 2025;15(2):1023-1038
Extensive evidence has demonstrated that glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorate obesity. Our previous studies revealed that (Ex-4)2-Fc, a long-acting GLP-1RA we developed, depends on the leptin pathway to treat obesity. However, the mechanisms linking (Ex-4)2-Fc and leptin resistance remain largely unclear. To address this question, we explored the mechanism of GLP-1RAs from the perspective of the gut microbiota, as increasing evidence indicates an important link between the gut microbiota and obesity. This study aimed to explore the potential role of the gut microbiota in the treatment of GLP-1RAs. We found that (Ex-4)2-Fc treatment reshaped obesity-induced gut microbiota disturbances and substantially increased the abundance of Akkermansia muciniphila (Am). In addition, (Ex-4)2-Fc did not respond well in antibiotic-treated (ATB) Obese mice. Subsequent studies have shown that this defect can be overcome by gavage with Am. In addition, we found that Am enhanced (Ex-4)2-Fc therapy by producing the metabolite inosine. Inosine regulates the macrophage adenosine A2A receptor (A2A) pathway to indirectly reduce leptin levels in adipocytes Thus, elucidating the role of metabolites in regulating the leptin pathway will provide new insights into GLP-1RAs therapy and may lead to more effective strategies for guiding the clinical use of antidiabetic agents.
3.Relationship between mechanism of preoperative sleep deprivation aggravating postoperative cognitive dysfunction and theta oscillations in hippocampal CA1 region in aged mice
Siwen LONG ; Feixiang LI ; Yize LI ; Yue YANG ; Bingqing GONG ; Yum LI ; Yonghao YU
Chinese Journal of Anesthesiology 2024;44(6):671-674
Objective:To evaluate the relationship between the mechanism of preoperative sleep deprivation aggravating postoperative cognitive dysfunction and theta oscillations in the hippocampal CA1 region in aged mice.Methods:Twenty-four SPF male C57BL/6J mice, aged 18 months, weighing 20-30 g, were divided into 3 groups ( n=8 each) by a random number table method: normal control group (group C), operation group (group S) and preoperative sleep deprivation + operation group (group SD+ S). The sleep deprivation model was established using the sleep deprivation rod method, and the sleep deprivation time was 24 h before operation. The sleep deprivation rod was set to rotate continuously at 6 rpm/min, and the direction was randomly reversed to force the mice to exercise to achieve the purpose of sleep deprivation. Group C received no treatment. Group S underwent exploratory laparotomy under isoflurane anesthesia. After sleep deprivation for 24 h, SD+ S group underwent exploratory laparotomy under isoflurane anesthesia. Y-maze and Morris water maze tests were used to evaluate postoperative cognitive function. The theta oscillations in the hippocampal CA1 region were observed and recorded by EEG electrodes in vivo. The animals were then sacrificed and brain tissues were obtained for determination of the density of dendritic spines in the hippocampal CA1 region. Results:Compared with group C, the number of crossing the original platform was significantly decreased, and the time of staying at the original platform quadrant and time of exploring the novel arm were shortened, and the number of entries into the novel arm was reduced, the density of dendritic spines in the hippocampal CA1 region was reduced, and the percentage of theta oscillation power was decreased during the Y maze test in group S ( P<0.05). Compared with S group, the number of crossing the original platform was significantly decreased, and the time of staying at the original platform quadrant and time of exploring the novel arm were shortened, and the number of entries into the novel arm was reduced, the density of dendritic spines in the hippocampal CA1 region was reduced, and the percentage of theta oscillation power was decreased during the Y maze test in SD+ S group ( P<0.01). Conclusions:The mechanisms by which preoperative sleep deprivation exacerbates postoperative cognitive dysfunction may be related to reduction in theta oscillations in the hippocampal CA1 region of aged mice.
4.Effect of emergency nursing process in hospital for acute massive hemoptysis based on business reengineering theory
Yan HE ; Yanjun MAO ; Zheng ZHANG ; Jun YANG ; Siwen MIN
Chinese Journal of Practical Nursing 2023;39(2):81-87
Objective:Based on the business reengineering theory, to construct the emergency nursing process of acute massive hemoptysis in hospital and explore the effect of it.Methods:According to the order of hospitalization, 200 patients with acute massive hemoptysis admitted to the emergency department in Shanghai Pulmonary Hospital Affilated to Tongji University from January to June in 2020 were selected as the control group, and the original treatment process was adopted. Two hundred patients admitted to the emergency department of this hospital from July to December in 2020 were selected as the experimental group, and the reconstructed in-hospital emergency nursing process for acute massive hemoptysis was applied. In both groups, the researchers recorded the time spent in each sub-process by using the in-hospital treatment time record of acute massive hemoptysis and collected the clinical outcomes of patients through electronic cases. The time-consuming, treatment efficiency and patient outcome of each link of the treatment process in the backyard of the two groups were compared.Results:Finally, 192 patients were enrolled in the control group and the experimental group. The median time from admission to intravenous use of hemostatic drugs and from admission to endovascular treatment in the experimental group were 21.50(20.00, 22.50) and 82.50(79.50, 84.50) min, which were lower than those in the control group which spent 40.87(37.06, 44.43) and 135.50(123.50, 147.00) min, and the differences between the two groups were statistically significant ( Z=-16.84, 16.63, both P<0.01). The incidence of asphyxia caused by acute massive hemoptysis in the experimental group was 4.2%(8/192), which was lower than that in the control group, which was 13.0%(25/192) . There was a statistically significant difference in the incidence of asphyxia between the two groups( χ2=9.58, P<0.01). Conclusions:The emergency nursing process of acute massive hemoptysis effectively shortens the time of in-hospital treatment of acute massive hemoptysis, further promotes the seamless connection of multiple links of in-hospital treatment of acute massive hemoptysis, and improves the overall efficiency of in-hospital treatment of patients with acute massive hemoptysis.
5.Study on the effects of 17-hydroxy-jolkinolide B on the proliferation and apoptosis of human triple-negative breast cancer cells
Fei GONG ; Siming WU ; Lei XU ; Yanan BAO ; Yu LIN ; Siwen PAN ; Dongxing YANG ; Cuicui HAN
China Pharmacy 2023;34(12):1415-1421
OBJECTIVE To study the effects of the active component 17-hydroxy-jolkinolide B (HJB) of Euphorbia fischeriana on the proliferation and apoptosis of human triple-negative breast cancers (TNBC) MDA-MB-231 and MDA-MB-468 cells. METHODS MTT assay was adopted to detect the inhibitory rate of MDA-MB-231 and MDA-MB-468 cells proliferation after treated with 0 (blank control),5,10,20,40,80 μmol/L HJB for 24, 48 and 72 h. Laser confocal microscope and flow cytometry were adopted to detect the apoptosis, mitochondrial membrane potential(MMP) and reactive oxygen species (ROS) of above 2 kinds of cells after treated with 0 (blank control), 10,20,40 μmol/L HJB for 24 h. Western blot assay was used to detect the expressions of B cell lymphoma-2( Bcl-2), Bcl-2-associated X protein (Bax), cytochrome-C (Cyt-C), caspase-3, cleaved caspase- 3, caspase-9 and cleaved caspase-9. RESULTS Compared with blank control group, 5,10,20,40,80 μmol/L HJB could significantly increase the inhibitory rate of MDA-MB-231 and MDA-MB-468 cells proliferation (P<0.05), in dose- and time- dependent trend. After 24 h treatment of HJB (10,20,40 μmol/L), the apoptosis of above 2 kinds of cells increased, and the total apoptotic rate increased significantly (P<0.05); the mitochondrial membrane potential decreased significantly (P<0.05); the level of ROS increased significantly (P<0.05); the protein expressions of Bcl-2, caspase-3 and caspase-9 were decreased significantly (P< 0.05), while the protein expressions of Cyt-C, Bax, cleaved caspase-3 and cleaved caspase-9 were increased significantly (P<0.05). CONCLUSIONS HJB can inhibit the proliferation of MDA-MB-231 and MDA-MB-468 cells, and induce their apoptosis.
6.Effects of different feeding patterns on weight gain and feeding intolerance in hospitalized premature infants
Yufang HU ; Jianying WU ; Yang YANG ; Siwen FENG ; Hong LU
Chinese Journal of Modern Nursing 2023;29(24):3316-3320
Objective:To explore the effects of different feeding patterns on weight gain and feeding intolerance in hospitalized premature infants.Methods:The retrospective cohort study design was adopted. From April 2019 to October 2020, 155 premature infants admitted to the Neonatal Intensive Care Unit of China-Japan Friendship Hospital were selected as the study subject by convenience sampling. Premature infants were divided into a mixed feeding group ( n=47) and a formula milk feeding group ( n=108) based on their feeding patterns. The observation indicators included weight gain, feeding intolerance, infectious diseases, nutrition and other related indicators. Results:The weight change value and the weight change rate during hospitalization in the mixed feeding group were higher than those in the formula milk feeding group, with statistically significant differences ( P<0.05) . In terms of the total milk volume on the day of discharge, the mixed feeding group were higher than the formula milk feeding group, and the differences were statistically significant ( P<0.05) . During hospitalization, the number of new infectious diseases in the mixed feeding group was less than that in the formula milk feeding group, with a statistically significant difference ( P<0.05) . There was no statistically significant difference in the incidence of feeding intolerance between the two groups of premature infants ( P>0.05) , The incidence of vomiting in the formula milk feeding group was lower than that in the mixed feeding group, with a statistically significant difference ( P<0.05) . Conclusions:Mixed feeding is more conducive to promoting the weight gain of premature infants during hospitalization and reducing the occurrence of infectious diseases than formula milk feeding. The impact of two feeding patterns on feeding intolerance in hospitalized premature infants needs further comparative analysis.
7.Prevalence characteristics and influencing factors of work-related musculoskeletal disorders in solar greenhouse workers
Xiaojun ZHU ; Siwen YANG ; Tenglong YAN ; Wei HE ; Yuqian WANG ; Xingfan ZHOU ; Wenjun MA ; Shichuan TANG ; Tao LI
Journal of Environmental and Occupational Medicine 2021;38(12):1295-1300
Background In the process of greenhouse working, labor intensity is high and repetitive work involves multiple body parts such as limbs, neck, upper back, and lower back. The prevalence and comorbidity of work-related musculoskeletal disorders (WMSDs) in greenhouse workers are worthy of attention. Objective This study is conducted to investigate the prevalence and comorbidity, as well as potential influencing factors of WMSDs in greenhouse workers. Methods A total of 722 greenhouse workers were selected as the subjects for a cross-sectional epidemiological survey. Through questionnaire survey and physical examination, basic information of the subjects and the prevalence of WMSDs were collected. The participants were divided into low, medium, and high cumulative exposure groups by cumulative exposure index matrix. Chi-square test was used to analyze the difference of prevalence among different cumulative exposure levels, the correlation between the prevalence of WMSDs in paired sites was calculated as prevalence ratio (PR) by using the log-binomial model, the prevalence of multi-site WMSDs in each group was compared by Wilcoxon rank sum test, and the influencing factors of multi-site WMSDs were evaluated by multi-classification logistic regression model. Results The prevalence rate of WMSDs in the greenhouse workers was 78.7% (568/722). The main affected sites of body were lower back, legs, neck, and shoulders, and associated prevalence rates were 47.6%, 46.0%, 27.1%, and 23.8%, respectively. By constructing a cumulative exposure index matrix, the low, medium, and high cumulative exposure groups contained 121, 196, and 405 workers respectively. The prevalence rates of WMSDs in lower back, legs, or shoulders were significantly different among groups with different exposure levels (P<0.05), and the prevalence rates increased with higher cumulative exposure levels (lower back,
8.Relationship between solar greenhouse working and anisometropia
Xiaojun ZHU ; Tenglong YAN ; Wei HE ; Siwen YANG ; Yuqian WANG ; Xingfan ZHOU ; Wenjun MA ; Shichuan TANG ; Tao LI
Journal of Environmental and Occupational Medicine 2021;38(12):1301-1306
Background Due to long working time and complex and changeable lighting conditions, greenhouse workers' anisometropia is an issue of concern. Objective This study is conducted to evaluate the relationship between solar greenhouse working and anisometropia of workers. Methods Subjects of a solar greenhouse group and a non-greenhouse group in northwest area of China were selected. Questionnaire survey was used to collect general demographicinformation. Standard Logarithmic Visual Acuity Chart (GB 11533—2011) was used to measure naked eye vision before working, the absolute value of binocular visual acuity difference was calculated and converted into classification variables, and both anisometropia absolute value and classification variables of anisometropia were used as indicators to compare the difference of the two groups. A cumulative exposure index that multiplies exposure time and number of greenhouses was further introduced to evaluate cumulative exposure levels of the greenhouse workers and was used to divide them into low, medium, and high cumulative exposure subgroups. Generalized linear model and logistic regression model were used to analyze possible risk factors associated with anisometropia. Results A total of 1002 subjects were enrolled in this study, including 739 workers in the greenhouse group and 263 workers in the non-greenhouse group. The medians (interquartile intervals) of anisometropia of the greenhouse group and non-greenhouse group were 0.1 (0, 0.2) and 0 (0, 0.1) respectively, and the difference was statistically significant (P<0.05). The proportions of anisometropia=0, ≤0.2, and >0.2 in the greenhouse group were 34.2%, 55.2%, and 10.6%, respectively, and those in the non-greenhouse group were 58.2%, 34.6%, and 7.2%, respectively. The difference of anisometropia distribution between the two groups was statistically significant (P<0.05). According to the cumulative exposure index, the greenhouse group was divided into low, medium, and high cumulative exposure subgroups, with 154 (21.0%), 188 (25.6%), and 392 (53.4%) workers, respectively. There was no statistical significance in anisometropia among workers with different cumulative exposure levels (P>0.05). The results of multiple generalized linear analysis showed that greenhouse working was a risk factor of anisometropia (b=0.053, P<0.05), and the results of multiple logistic regression analysis showed that greenhouse working was associated with an increased risk of anisometropia (OR=2.586, 95%CI: 1.473-4.539). The results of multiple generalized linear analysis showed that medium exposure level increased the degree of anisometropia after adjusting age, gender, and other factors (b=0.054, P<0.05). Conclusion Solar greenhouse working may be a risk factor for increasing anisometropia in workers.
9.Characteristics of blood lipid in solar greenhouse workers
Tenglong YAN ; Siwen YANG ; Yuqian WANG ; Xiaojun ZHU ; Xingfan ZHOU ; Wenjun MA ; Shichuan TANG ; Jue LI ; Tao LI
Journal of Environmental and Occupational Medicine 2021;38(12):1307-1311
Background As a new type of vegetable production method, solar greenhouse has been widely promoted nationwide. The influence of solar greenhouse working on blood lipid cannot be ignored. Objective The aim of the study is to explore the relationship between solar greenhouse working and blood lipid and family clustering. Methods A total of 744 solar greenhouse workers in northwestern China were selected as the greenhouse group, and 231 general open field farmers in the same area were selected as the non-greenhouse group. The levels of serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC) in the two groups were detected. Dyslipidemia was determined by a two-classification criteria in the national guideline of 2007. Multiple logistic regression model and multilevel multiple linear regression model were used to explore the relationship of blood lipid with solar greenhouse working, and its family clustering. Results The number of dyslipidemia cases in the greenhouse group and non-greenhouse group was 142 (19.1%) and 43 (18.6%), respectively, and the difference was not statistically significant (P>0.05). The results of multiple logistic regression analysis showed that increasing age (OR=1.019, 95% CI: 1.001-1.038) and increased BMI (OR=1.162, 95% CI: 1.106-1.220) were related to elevated risk of dyslipidemia (all Ps<0.05). The results of multilevel multiple linear regression model showed that the changes of TC, HDLC, and TG/HDLC had family clustering (b=0.238, 95%CI: 0.132-0.430; b=0.044, 95%CI: 0.033-0.065; b=1.003, 95%CI: 0.947-1.059) (all Ps<0.05). Conclusion Solar greenhouse working does not significantly increase the incidence of dyslipidemia, but the levels of TC, HDLC, and TG/HDLC levels in the solar greenhouse workers have family clusters.
10.Relationships between solar greenhouse working and selected blood biochemical indexes of elderly workers
Tenglong YAN ; Siwen YANG ; Yuqian WANG ; Xiaojun ZHU ; Xingfan ZHOU ; Wenjun MA ; Shichuan TANG ; Jue LI ; Tao LI
Journal of Environmental and Occupational Medicine 2021;38(12):1312-1317
Background The aging of the labor force has become a global trend, and various occupational activities can affect blood biochemical indexes and increase the risk of metabolic diseases. Elderly workers are the main laborers in the solar greenhouse industry, and their blood biochemical indexes need more attention. Objective The purpose of this study is to explore the alternation of selected blood biochemical indexes and provide clues for conducting management programs of metabolic diseases in the elderly solar greenhouse workers. Methods The research subjects of the greenhouse group and the non-greenhouse group were selected from a vegetable production base in Northwest China. The elderly workers were selected from a recruited subjects pool for an earlier project by means of matching and non-matching respectively. The matching conditions were gender (consistent), age (±2 years old), body mass index (BMI) (±1 kg·m−2), education level (±1 level), smoking (consistent), and drinking (consistent). Routine clinical tests were used to detect serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), fasting blood glucose (GLU), and albumin (ALB), and single-factor and multi-factor analyse were used to identify different indexes in matching and non-matching samples, respectively. The matching and the non-matching samples included 80 pairs of subjects and 327 subjects, respectively. Results In the matching sample set, the greenhouse group's HDLC [(1.61±0.34) mmol·L−1] was lower than the non-greenhouse group's [(2.09±0.37) mmol·L−1] (P<0.05), the level of TG/HDLC in the greenhouse group was (1.17±0.74), higher than that in the non-greenhouse group (0.78±0.47) (P<0.05), and the level of LDLC/HDLC in the greenhouse group was (1.87±0.36), also higher than that in the non-greenhouse group(P<0.05), while there was no statistical difference of the other indexes between the two groups (all Ps>0.05). In the non-matching sample set, the results of multiple linear regression analysis showed that solar greenhouse working correlated with decreased HDLC, and increased TG/HDLC and LDLC/HDLC among the elderly workers (all Ps<0.05). Conclusion Solar greenhouse working may correlate with variations of selected blood biochemical indexes in elderly workers, and the occupational health surveillance of elderly workers should be strengthened.

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