1.KDM5A/cGAS-STING–mediated microglial activation contributes to prenatal fine particulate matter induced cerebral cortical injury in offspring mice
Wenke NIE ; Li ZHOU ; Siqi WANG ; Chao SONG ; Hang YU ; Wanwei LI ; Mengxiao LUAN ; Lu SUN ; Li YU
Journal of Environmental and Occupational Medicine 2026;43(3):270-277
Background Prenatal exposure to fine particulate matter (PM2.5) is closely associated with cortical damage and neuroinflammation in offspring. The cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway is a key regulator of inflammation and may be subject to epigenetic regulation. Objective To investigate the role of cGAS-STING pathway activation in PM2.5-induced cortical damage in offspring mice during pregnancy and the underlying epigenetic regulatory mechanisms. Methods Open field tests were used to assess depressive-like behavior in offspring mice. Morphological analysis was conducted to evaluate cortical damage and microglial activation in offspring brains. Real-time fluorescent quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect changes in the expression of key molecules in the cGAS-STING pathway in cortical tissue. A PM2.5-induced microglial cell injury model was established in BV2 cells. Microglial activation was observed, cell viability was measured using the Cell Counting Kit-8 (CCK-8), and the expression levels of inducible nitric oxide synthase (iNOS) and key molecules in the cGAS-STING pathway were detected by RT-qPCR and WB. Bioinformatics analysis was performed to explore the epigenetic regulatory association between the STING signaling pathway and lysine-specific demethylase 5A (KDM5A). Changes in KDM5A mRNA and protein expression, as well as the protein level of histone H3 lysine 4 trimethylation (H3K4me3), were detected in an in vitro PM2.5 injury model. Using small interfering RNA (siRNA) technology, the KDM5A gene was silenced in BV2 cells exposed to PM2.5. The protein expression of H3K4me3 was detected to evaluate improvements in microglial activation, changes in inflammatory markers such as iNOS and mannose receptor (CD206), and alterations in the cGAS-STING pathway. Results Compared with the control group, the total distance of offspring mice in the PM2.5 group was significantly reduced, and both the distance traveled and the time spent in the central area of the open field were significantly decreased (P<0.01, P<0.001), indicating depressive-like behavior in the offspring mice. Compared with the control group, the offspring mice in the PM2.5 group exhibited disorganized cortical structure and significantly activated microglia (P<0.01), with significantly increased mRNA and protein levels of cGAS and STING (P<0.05, P<0.01, or P<0.001). The in vitro experiments demonstrated that the PM2.5 treatment induced BV2 cells to polarize toward the M1 phenotype, exhibiting a distinct amoeboid morphology, with upregulated expression of the pro-inflammatory factor iNOS (P<0.05, P<0.01, or P<0.001) and activation of the cGAS-STING pathway (P<0.05, P<0.01). The analysis of RNA-seq data from KDM5A knockout cells revealed significantly downregulated STING expression, suggesting that KDM5A may activate the STING signaling pathway. The in vitro experiments further confirmed that the PM2.5-treated BV2 cells exhibited significantly elevated mRNA and protein levels of KDM5A (P<0.01), while the H3K4me3 protein levels were markedly reduced (P<0.05). After silencing KDM5A in BV2 cells exposed to PM2.5, compared with the PM2.5+siNC group, the PM2.5+siKDM5A group showed no obvious microglial activation and polarized toward the M2 phenotype, with significantly decreased expression levels of iNOS, cluster of differentiation 16 (CD16), and interleukin-1β (P<0.05, P<0.01), and significantly increased expression levels of anti-inflammatory factors CD206, YM1, and interleukin-10 (P<0.01, P<0.001). Meanwhile, the expression levels of cGAS and STING were also reduced (P<0.05, P<0.01). Conclusion KDM5A activates microglia through the cGAS-STING pathway, thereby contributing to PM2.5-induced cortical damage in offspring mice during pregnancy.
2.Regulatory role and mechanism of lactate in metabolic dysfunction-associated fatty liver disease
Wenke SUN ; Jishuang SAN ; Jiancheng YANG
Journal of Clinical Hepatology 2026;42(8):1939-1945
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a chronic liver disease with a persistently high prevalence rate worldwide. Its pathogenesis involves metabolic disorders in multiple systems, and there is still a lack of a complete theoretical regulatory framework. Lactate was once regarded as a terminal metabolic waste product of the glycolytic pathway; however, studies in recent years have been exploring its biological functions as a key signaling molecule, and the close association between dysregulated lactate metabolism and the development and progression of MAFLD has gradually become a research hotspot in the field of metabolic liver diseases. This article systematically introduces the core pathways and regulatory patterns of lactate metabolism, elaborates on the overall functional characteristics of lactate in the development and progression of MAFLD, and reviews the molecular mechanisms by which lactate mediates hepatic lipid metabolism disorders and drives inflammatory cascades through epigenetic regulatory mechanisms such as protein lactylation. In addition, it briefly describes the potential effect of lactate in modulating liver metabolic homeostasis via the gut-liver axis and summarizes the latest research advances in lactate metabolism and MAFLD. This article highlights that targeting lactate metabolic pathways is a critical entry point for deepening the understanding of the pathophysiological mechanisms of MAFLD, and it points out that non-canonical regulatory modes represented by lactylation are key breakthrough directions for future research. It also proposes that developing early diagnostic biomarkers and intervention targets for MAFLD based on the lactate metabolic network holds important theoretical value and clinical translation potential.
3.Detection and clinical significance of serum FGF23 and 25-OH-VD levels in children with osteoporosis
Nuan HAN ; Wenke CHEN ; Sainan WANG ; Tao LI ; Tixue WANG ; Jinsong SUN
Chinese Journal of Endocrine Surgery 2025;19(4):579-583
Objective:To analyze the relationship among serum levels of fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D (25-OH-VD) and osteoporosis in children.Methods:Eighty children with osteoporosis admitted to Affiliated Hosptial of Jining Medieal University from Jun. 2019 to Jun. 2024 were included as the observation group, and 60 healthy children who underwent physical examination during the same period were included as the control group. Serum FGF23 and 25-OH-VD levels were compared between the two groups, and bone mineral density and bone metabolism indexes [CTX-1, osteocalcin (OC) and N-terminal propeptide of type I precollagen (PINP) ] were detected. Pearson correlation was used to analyze the correlation among serum FGF23, 25-OH-VD, bone metabolism indexes and bone mineral density. Logistic regression model was used to analyze the risk factors of osteoporosis in children.Results:Serum FGF23 and CTX-1 levels in the observation group were significantly higher than those in the control group ( t=15.77, 7.56, P < 0.05), while serum 25-OH-VD, OC, PINP and BMD levels were significantly lower ( t=14.09, 2.70, 13.25, 3.63, P < 0.05) ; Pearson correlation analysis showed that BMD was not correlated with age, BMI and OC ( r=-0.07, -0.02, 0.01, P > 0.05), BMD was negatively correlated with FGF23 and CTX-1, and positively correlated with 25-OH-VD and PINP ( r=-0.35, -0.34, 0.41, 0.40, P < 0.05). The stepwise regression model showed that FGF23 and 25-OH-VD were the main factors affecting BMD ( t=-2.40, 9.02, P<0.05). Multifactor Logistic regression model showed that FGF23 and 25-OH-VD were related factors of osteoporosis in children ( OR=3.01,1.16, P<0.05) . Conclusion:Serum FGF23 level is higher and 25-OH-VD level is lower in children with osteoporosis, which is significantly correlated with bone mineral density and is a related factor for osteoporosis in children.
4.Detection and clinical significance of serum FGF23 and 25-OH-VD levels in children with osteoporosis
Nuan HAN ; Wenke CHEN ; Sainan WANG ; Tao LI ; Tixue WANG ; Jinsong SUN
Chinese Journal of Endocrine Surgery 2025;19(4):579-583
Objective:To analyze the relationship among serum levels of fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D (25-OH-VD) and osteoporosis in children.Methods:Eighty children with osteoporosis admitted to Affiliated Hosptial of Jining Medieal University from Jun. 2019 to Jun. 2024 were included as the observation group, and 60 healthy children who underwent physical examination during the same period were included as the control group. Serum FGF23 and 25-OH-VD levels were compared between the two groups, and bone mineral density and bone metabolism indexes [CTX-1, osteocalcin (OC) and N-terminal propeptide of type I precollagen (PINP) ] were detected. Pearson correlation was used to analyze the correlation among serum FGF23, 25-OH-VD, bone metabolism indexes and bone mineral density. Logistic regression model was used to analyze the risk factors of osteoporosis in children.Results:Serum FGF23 and CTX-1 levels in the observation group were significantly higher than those in the control group ( t=15.77, 7.56, P < 0.05), while serum 25-OH-VD, OC, PINP and BMD levels were significantly lower ( t=14.09, 2.70, 13.25, 3.63, P < 0.05) ; Pearson correlation analysis showed that BMD was not correlated with age, BMI and OC ( r=-0.07, -0.02, 0.01, P > 0.05), BMD was negatively correlated with FGF23 and CTX-1, and positively correlated with 25-OH-VD and PINP ( r=-0.35, -0.34, 0.41, 0.40, P < 0.05). The stepwise regression model showed that FGF23 and 25-OH-VD were the main factors affecting BMD ( t=-2.40, 9.02, P<0.05). Multifactor Logistic regression model showed that FGF23 and 25-OH-VD were related factors of osteoporosis in children ( OR=3.01,1.16, P<0.05) . Conclusion:Serum FGF23 level is higher and 25-OH-VD level is lower in children with osteoporosis, which is significantly correlated with bone mineral density and is a related factor for osteoporosis in children.
5.The Development Strategy and Mode of Co-construction and Sharing Base to Improve the Chinese Herbal Medicine Quality
Wenke ZHENG ; Jianhe WEI ; Shilin CHEN ; Xiaobo SUN ; Shuangcheng MA ; Boli ZHANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2018;20(11):1905-1910
Chinese medicinal materials occupy an important position in China's health industry. However, its overall quality needs to be improved and it is in urgent need of regulation. Exploring the formation of effective organizational mechanisms and industry models has become an urgent need of the industry. In this context, the alliance of coconstruction and sharing Chinese herbal medicine base came into being. The alliance is based on the pursuit of the quality of Chinese herbal medicines and continues to promote the construction of Chinese herbal medicines. The Alliance provides a platform for economic and scientific cooperation in the industry. Its purpose is to guide the promotion of the standardization of local varieties and the construction of modern Chinese medicine agricultural enterprises based on the development needs of Chinese herbal medicine resources and the common interests of all members. As an important content, we will strive to expand the new pattern of coordinated development of traditional Chinese medicine agriculture and industry, explore the establishment of a new organizational system for modern Chinese medicine agricultural production with controllable quality, output and price under the link of production and demand. For the sustainable, stable and healthy development of the Chinese medicine industry, it will serve 1.3 billion people and serve humanity, provide high-quality sustainable Chinese herbal medicine resources. Since its establishment six years ago, the alliance has carried out work on key aspects such as standardized production of Chinese herbal medicines, plant protection, decoction processing, supply and demand docking, medicinal materials standards, poverty alleviation, breeding, and provided technical support to enterprises. During this period, the alliance also proposed the concept of"three-no and one- all"requires the members to take the lead in achieving the standards of"sulfur- free processing, no aflatoxin pollution, pollution-free, traceable throughout the whole", setting a benchmark for the industry.
6.Investigation on Medical Students′Recognition Degree of Cross Transplantation between Non Relatives
Lan WANG ; Wenke ZHAO ; Xiaoqian ZHANG ; Xiaohui SUN ; Juanhong ZHOU ; Liu YANG
Chinese Medical Ethics 2016;29(4):635-638
Objective:Living organ transplantation prolongs the life of many dying patients, but there are many disputes, especially the definition ofliving organ transplantation between non relatives. The definition of this ter-minology is closely related to medical students′cognitive ofliving organ transplantation between non relatives. The medical students are the main reserve army of medical staff and the executor of living donor organ transplantation in the future, who directly determine the organ transplantation and affect the doctor-patient relationship. This paper is to investigate and analyze the status of the medical students′recognition of cross transplantation between non rela-tives. Methods:A total of 450 medical students of Qingdao university were selected with cluster method and were investigated using self-designed questionnaire. Data were analyzed by SPSS 22. 0. Results:The overall recogni-tion rate toliving organ cross transplantation between non relatives was relatively low. The difference was statisti-cally significant (P<0. 05), namely that students in higher grade had lower recognition. The difference was statis-tically significant (P < 0. 05) between different specialties, and the recognition degree of students majoring in clinical medicine and ecsomatics was higher. Conclusion:The medical students of Qingdao University understand the concept of living organ cross transplantation between non relativesfuzzily, and the recognition degree is low.
7.Protective effect of ischemic postconditioning on rat models of lung ischemia/reperfusion injury
Lei SUN ; Wenya LI ; Wenke LIU ; Lin ZHANG
Chinese Journal of Tissue Engineering Research 2015;(27):4271-4276
BACKGROUND:Pneumonectomy, extracorporeal circulation, lung transplantation and pulmonary embolism can cause ischemia/reperfusion injury of lung tissue. Lung ischemia/reperfusion injury is an important factor of lung function disorders after lung transplantation. OBJECTIVE:To analyze the effect of ischemic postconditioning on rat models of lung ischemia/reperfusion injury. METHODS:Twenty-four male SD rats were randomly divided into sham, ischemia/reperfusion and ischemic postconditioning groups (n = 8 rats/group) to establish the lung ischemia/reperfusion injury model. The rats in the sham group were only subjected to separation of the hilum of left lung and pulmonary arteries and veins, without blocking. The rats in the ischemia/reperfusion group were subjected to another 2 hours of reperfusion after 1 hour of lung ischemia. The rats in the ischemic postconditioning group were first subjected to 30 seconds of lung ischemia and 30 seconds of reperfusion for three times, and then to 2 hours of reperfusion. After the experiment, the specimens of lung tissue were obtained to detect the wet/dry weight ratio of lung tissue, activities of superoxide dismutase, malondialdehyde and myeloperoxidase, the contentsof inflammatory cytokines tumor necrosis factor α, interleukin-1β and interleukin-6, and the histopathological changes of lung tissue were observed. RESULTS AND CONCLUSION:Compared with the sham group, the wet/dry weight ratio of lung tissue, activities of myeloperoxidase and myeloperoxidase, the levels of tumor necrosis factor α, interleukin-1β and interleukin-6 were significantly increased (P < 0.05) in the ischemia/reperfusion and ischemic postconditioning groups, however, the increase levels of these indices were not significant in the ischemic postconditioning group, and the contents and activities in the ischemic postconditioning group were al significantly decreased (P < 0.05) compared with those in the ischemia/reperfusion group. In the ischemia/reperfusion and ischemic postconditioning groups, the activity of superoxide dismutase was obviously lower than that in the sham group, however, the activity of superoxide dismutase in the ischemic postconditioning group was obviously higher than that in the ischemia/reperfusion group. Pathological examination showed that thickened alveolar wal, edema and a large amont of inflammatory cel infiltrations were observed in the lung tissue of rats in the ischemia/reperfusion group. The degrees of alveolar wal thickening and edema in the lung tissue of rats in the ischemic postconditioning group were mild compared with the ischemia/reperfusion group, and in addition, some inflammatory cels were infiltrated. The histopathological scores of lung tissue in the ischemic postconditioning group were lower than those in the ischemia/reperfusion group. These results suggest that ischemic postconditioning plays its protective role on rat models of ischemia/reperfusion injury by inhibiting inflammatory cel accumulation, oxygen free radical production and pro-inflammatory cytokine release after ischemia/reperfusion injury.
8.Intervention effect of the mode of monitoring-training-planning on rational use of antibacterials in upper respiratory infection in outpatient clinic of respiratory department
Weiguo CHEN ; Yuexiu CAI ; Qikai LU ; Yinxiang SUN ; Yi ZHOU ; Jinsong ZHONG ; Wenke SHI ; Changfeng LI
Chinese Journal of Practical Internal Medicine 2002;0(08):-
Objective To study the effect of the intervention mode of MTP on use of antibacterials in upper respiratory infection.Methods Adopt retrospective method to select randomly prescriptions of upper respiratory infection from July to September in 2006 for baseline investigation in Outpatient Clinic of Respiratory Department of the First People's Hospital of the city of Zhuhai in Guangdong province.Then aim physicians was interfered by MTP and investigation of post-interference was carried out after a month.The process of intervention and investigation was carried out repeatedly until June in 2007.The ratio of antibacterials use,injection use percentage and average drug fee was observed in pre/post-interference.Results The ratio of antibacterials use in upper respiratory infection in our hospital was decreased from 81.33% to 0,and the ratio percentage of injection use and average drug fee decreased by 81.69% and 35.47% respectively after four MTP circulations.Conclusion The intervention mode of MTP is feasible and effective on promoting the rational use of antibacterials on upper respiratory infection in Outpatient Clinic of Respiratory Department of our hospital.
9.Effects of antibiotic treatment on the inflammatory mediator expression in peritoneum and the peritoneal transport function in the rat with acute bacterial peritonitis
Zhanjun JIA ; Xueqing YU ; Xin WANG ; Xiaoyan LI ; Wenfang CHEN ; Wenxing PENG ; Xianrui DOU ; Wenke HAO ; Liao SUN ; Zhihua ZHENG ; Peida YIN
Chinese Journal of Pathophysiology 2000;0(07):-
AIM: To observe the effect of antibiotic treatment on the inflammatory mediator expression in peritoneum and the peritoneal transport function in rats with acute peritonitis, and explore its mechanisms. METHODS: Eighty-six SD rats were randomly divided into three groups. Control group (n=28) were treated with PBS (ip), peritonitis group (n=28) and treatment group (n=28) were challenged with the E.coli (ip), but at 3 h and 9 h gentamicin was given (ip) in treatment group. Seven rats of every group were randomly sacrificed at 24 h, 48 h, 72 h and 7 d. Peritoneal equilibration test (PET) was did before they were killed. Leukocyte count, pathological changes and the expression of CD45, NF-?B, IL-1?, TNF-? in peritoneum were examined. RESULTS: (1)The blood leukocytes in peritonitis group decreased strikingly, but did not change obviously in other two groups. The peritoneal fluid leukocytes in peritonitis group increased significantly from 24 h to 72 h, while in treatment group, it enhanced more strikingly than peritonitis group at 24 h, and recovered earlier. (2) Both in peritonitis group and treatment group, the expression of activated NF-?B, IL-1?, TNF-? and CD45 increased significantly, but the treatment group was lower than model group at 48 h and 72 h. The mRNA level of IL-1? and TNF-? had the same trend as their protein expression. (3) Compared with the control group, UF and D/D_0 Glu decreased significantly in model group and treatment group, and D/PTP increased dramatically. The D/P TP in treatment group lowered obviously compared with peritonitis group, while the net UF and D/D_0 Glu had not significant difference between treatment group and model group. CONCLUSION: Antibiotic treatment can partly decrease the expression of inflammatory mediators in peritoneum of rats with acute peritonitis and also can improve the protein transport ability to some extent, but can not improve the peritoneal ultrafiltration and the glucose transport function.

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