1.eIF3a function in immunity and protection against severe sepsis by regulating B cell quantity and function through m6A modification.
Qianying OUYANG ; Jiajia CUI ; Yang WANG ; Ke LIU ; Yan ZHAN ; Wei ZHUO ; Juan CHEN ; Honghao ZHOU ; Chenhui LUO ; Jianming XIA ; Liansheng WANG ; Chengxian GUO ; Jianting ZHANG ; Zhaoqian LIU ; Jiye YIN
Acta Pharmaceutica Sinica B 2025;15(3):1571-1588
eIF3a is a N 6-methyladenosine (m6A) reader that regulates mRNA translation by recognizing m6A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m6A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m6A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.
2.Modulation of Ryanodine Receptors on Microglial Ramification, Migration, and Phagocytosis in an Alzheimer's Disease Mouse Model.
Yulin OUYANG ; Zihao CHEN ; Qiang HUANG ; Hai ZHANG ; Haolin SONG ; Xinnian WANG ; Wenxiu DONG ; Yong TANG ; Najeebullah SHAH ; Shimin SHUAI ; Yang ZHAN
Neuroscience Bulletin 2025;41(11):2063-2077
Microglial functions are linked to Ca2+ signaling, with endoplasmic reticulum (ER) calcium stores playing a crucial role. Microglial abnormality is a hallmark of Alzheimer's disease (AD), but how ER Ca2+ receptors regulate microglial functions under physiological and AD conditions remains unclear. We found reduced ryanodine receptor 2 (Ryr2) expression in microglia from an AD mouse model. Modulation of RyR2 using S107, a RyR-Calstabin stabilizer, blunted spontaneous Ca2+ transients in controls and normalized Ca2+ transients in AD mice. S107 enhanced ATP-induced migration and phagocytosis while reducing ramification in control microglia; however, these effects were absent in AD microglia. Our findings indicate that RyR2 stabilization promotes an activation state shift in control microglia, a mechanism impaired in AD. These results highlight the role of ER Ca2+ receptors in both homeostatic and AD microglia, providing insights into microglial Ca2+ malfunctions in AD.
Animals
;
Microglia/pathology*
;
Alzheimer Disease/pathology*
;
Phagocytosis/drug effects*
;
Ryanodine Receptor Calcium Release Channel/metabolism*
;
Disease Models, Animal
;
Mice
;
Cell Movement/drug effects*
;
Mice, Transgenic
;
Calcium Signaling/physiology*
;
Calcium/metabolism*
;
Mice, Inbred C57BL
;
Male
;
Endoplasmic Reticulum/metabolism*
3.Relationship between post-traumatic stress disorder and sleep
Jingye ZHAN ; Runda JIAO ; Hui OUYANG ; Weizhi LIU ; Lili WU
Academic Journal of Naval Medical University 2024;45(9):1147-1155
Post-traumatic stress disorder (PTSD),with the principal manifestations as invasive thinking,avoidance,negative emotions and cognition,and increased alertness,is a psychological disorder occurring after traumatic events. Sleep disorders are also considered as one of the core characteristics of PTSD. Previous studies have partly revealed the relationship between PTSD and sleep disorders,but the physiological mechanism of the relationship is still unclear. This article provides an overview of the clinical and physiological characteristics of PTSD and sleep disorders. Based on this,the bidirectional relationship between PTSD and sleep disorders is discussed,and the relevant physiological and brain mechanisms of the relationship between them are further explored. Future research needs to explore the neurophysiological mechanisms underlying the bidirectional relationship between PTSD and sleep by exploring the brain regions and neural circuits associated with both PTSD and sleep,providing more information and methods for the prevention and treatment of PTSD and sleep disorders.
4.Inhibition of Pannus Formation by Wutoutang in AIA Rats with Wind-cold-dampness Bi Syndrome Via Down-regulating HIF-1α/VEGFA/Ang Signaling Pathway
Dan OUYANG ; Xin LI ; Gangxiang ZHAN ; Zheng CHEN ; Yuanzhi MA ; Jie ZOU ; Jianzhong CAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):10-18
ObjectiveThis study aims to investigate the inhibitory effect of Wutoutang on pannus formation in adjuvant-induced arthritis (AIA) rats with wind-cold-dampness Bi syndrome and its potential mechanism. MethodA total of 40 male SD specific pathogen-free (SPF) rats were selected and divided into blank group, wind-cold-dampness Bi syndrome group [Complete Freund's Adjuvant (CFA), 200 μg], Wutoutang group (15 g·kg-1·d-1), and indometacin group (10 mg·kg-1) according to random number table method. Except for the blank group, the other groups were given wind-cold-dampness stimulation before the CFA injection. After the rats were administered for 30 days, the basic conditions, onset time, arthritis index score, and foot swelling volume of AIA rats with wind-cold-dampness Bi syndrome were observed. Finally, peripheral arterial blood, ankle joint, and synovial tissue were taken. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor A (VEGFA) protein content, and rheumatism, including anti-O (ASO), C-reactive protein (CRP), and rheumatoid factor (RF). Hematoxylin-eosin (HE) staining revealed the changes in joint histomorphology. Immunohistochemistry was used to detect the expression of HIF-1α and VEGFA, two important proteins in the ankle pathway. Quantitative real-time polymerase chain reaction (Real-time PCR) was used to reveal mRNA levels of HIF-1α, VEGFA, angiopoietin-1 (Ang-1), and angiopoietin-2 (Ang-2) in rat synovial tissue. ResultThe foot swelling volume and arthritis score of AIA rats with wind-cold-dampness Bi syndrome were substantially higher (P<0.01) compared with the blank group. Serum CRP, RF, and ASO levels were considerably elevated (P<0.01). HE staining showed obvious hyperplasia of ankle synovium and synovial inflammation, angiogenesis and pannus formation, and aggravated bone destruction, indicating successful modeling. After the intervention of Wutoutang, the onset time was delayed (P<0.01). Foot swelling volume and arthritis score were decreased (P<0.01). Serum CRP, RF, and ASO levels were significantly decreased (P<0.01). The inflammatory hyperplasia of synovial tissue, angiogenesis and pannus formation, and bone destruction were alleviated. The mRNA levels of HIF-1α, VEGFA, Ang-1, and Ang-2 in the synovial membrane were significantly decreased (P<0.05, P<0.01). The expressions of HIF-1α and VEGFA in serum and ankle joints were decreased (P<0.01). In the indomethacin group, the onset time of the disease was delayed (P<0.01). Foot swelling volume and arthritis score were decreased (P<0.01). Serum CRP, RF, and ASO levels were significantly decreased (P<0.01). HIF-1α/VEGFA/Ang signaling pathway was activated, and pathological tissue injury was improved. ConclusionWutoutang can delay the onset time of AIA rats with wind-cold-dampness Bi syndrome, reduce foot swelling volume, arthritis score, rheumatic activity, and improve joint histopathology. It can inhibit pannus formation, and its mechanism may be related to down-regulating the expression of the HIF-1α/VEGFA/Ang pathway.
5.Correlation between triglyceride-glucose index and high on-treatment platelet reactivity during clopidogrel treatment in patients with ischemic stroke
Haoxuan CHEN ; Li YANG ; Zhenzhen LOU ; Yibo ZHAN ; Huiying OUYANG ; Guixian CHEN ; Changlin ZHANG ; Hui MAO ; Xiaojun LI ; Zhiping HUANG ; Zequan ZHENG ; Haoyou XU ; Longlong WEN ; Min ZHAO ; Yuanqi ZHAO
International Journal of Cerebrovascular Diseases 2023;31(4):253-258
Objective:To investigate the correlation between triglyceride-glucose (TyG) index and high on-treatment platelet reactivity (HTPR) during clopidogrel treatment in patients with ischemic stroke.Methods:Patients with ischemic stroke who received maintenance dose of clopidogrel (75 mg/d) in the Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine from January 2017 to March 2021 were retrospectively included. The highest quartile (Q4) of the TyG index was defined as insulin resistance. Platelet reactivity was assessed by thromboelastogram and clopidogrel HTPR was defined as the clot strength induced by adenosine diphosphate (MA ADP) >47 mm. Multivariate regression model was used to analyze the independent correlation between TyG index and platelet reactivity. Results:A total of 83 patients were included. The TyG index showed a linear correlation with MA ADP. The patients were divided into 4 groups according to the quartile of TyG index. The incidence of clopidogrel HTPR increased significantly with the increase of the quartile of the TyG index ( Ptrend=0.017). Multivariate analysis showed that there was a significant independent correlation between insulin resistance and clopidogrel HTPR (odds ratio 4.597, 95% confidence interval 1.285-16.446; P=0.019). Conclusions:In patients with ischemic stroke treated with clopidogrel, the incidence of clopidogrel HTPR gradually increases with the increase of the quartile of the TyG index. The insulin resistance assessed by the TyG index is independently associated with clopidogrel HTPR.
6.Influence of herbal cake-partitioned moxibustion on lumbar functions and inflammatory factors in patients with lumbar disc herniation due to kidney deficiency and blood stasis
Dingyan BI ; Hongliang LI ; Dao HE ; Jianan CAO ; Lizhi OUYANG ; Huijuan LIU ; Jing WANG ; Zhan YI ; Kaiwei ZHANG
Journal of Acupuncture and Tuina Science 2022;20(5):370-375
Objective: To observe the efficacy of herbal cake-partitioned moxibustion for lumbar disc herniation (LDH) due to kidney deficiency and blood stasis and observe the influence of this method on lumbar functions and inflammatory factors in patients with this condition. Methods: A total of 120 LDH patients who met the inclusion criteria were randomly divided into three groups, including a herbal cake-partitioned moxibustion group, a flour cake-partitioned moxibustion group, and a Western medication group, with 40 patients in each group. The patients in the Western medication group were treated with diflunisal tablets, 0.5 g per dose, 2 doses a day. Those in the herbal cake-partitioned moxibustion group were treated with additional herbal cake-partitioned moxibustion group at Back-Shu Points and Jiaji (EX-B2) Points once a day. Those in the flour cake-partitioned moxibustion group were treated with the same methods as in the herbal cake-partitioned moxibustion group, except that the herbal cake was replaced by a flour cake. All the patients were treated for 10 d. After treatment, the scores of the visual analog scale (VAS) and Japanese Orthopaedic Association (JOA) and the changes of the interleukin (IL)-6, tumor necrosis factor (TNF)-α, and substance P (SP) levels were observed, and the efficacy was evaluated. Results: After treatment, the VAS score and the levels of IL-6, TNF-α, and SP were lower than those before treatment, and the JOA score was higher than that before treatment in the three groups, indicating intra-group statistical significance (P<0.05). The VAS score and the levels of IL-6, TNF-α, and SP of the herbal cake-partitioned moxibustion group were lower than those of the flour cake-partitioned moxibustion group and the Western medication group, while the JOA score of the herbal cake-partitioned moxibustion group was higher than that of the other two groups, indicating inter-group statistical significance (P<0.05). The total effective rate of the herbal cake-partitioned moxibustion group was 92.5%, higher than that of the flour cake-partitioned moxibustion group (80.0%) and the Western medication group (72.5%), indicating inter-group statistical significance (P<0.05). Conclusion: On the basis of Western oral medication, additional herbal cake-partitioned moxibustion can alleviate the pain and improve the lumbar functions in patients with LDH due to kidney deficiency and blood stasis. The efficacy of the integrated method is better than that of either flour cake-partitioned moxibustion or Western medication alone, which may be related to the reduction of serum inflammatory factors.
7.Herbal Textual Research on Mori in Famous Classical Formulas
Wen-min DU ; Zhi-lai ZHAN ; Jing-qiong WAN ; Tian-yue LIAO ; Hui JIANG ; Zhao-yong ZHOU ; Zhen OUYANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(10):11-21
Through consulting the ancient herbs, medical books and modern literature, this paper made textual research on the name, origin, producing area, quality evaluation, collection and processing of medicinal materials of Sang (Mori Folium, Mori Cortex, Mori Ramulus, Mori Fructus) in famous classical formulas, in order to provide a basis for the development of famous classical formulas containing medicinal materials of Sang. According to the research, Mori Folium and Mori Cortex were first used as medicines in Shengnong Bencaojing , Mori Ramulus was first used as medicine in Jinxiaofang, and Mori Fructus was first used as medicine in Xinxiu Bencao. Before the Tang dynasty, there were Nyusang and Shansang. Since Tang dynasty, there were many sources of medicinal materials of Sang, including Baisang (Morus alba), Jisang (M. australis), Shansang (M. mongolica), etc. According to textual research, the mainstream varieties were M. australis, M. alba and their cultivated varieties. In modern times, according to the relevant information and the Chinese Pharmacopoeia, M. alba is the original base. In ancient times, the origin of mulberry changed with the development of sericulture, mulberry has been widely planted since the Song dynasty. In the Ming and Qing dynasties, mulberry has been planted most in Jiangsu and Zhejiang. In modern times, they are mainly produced in Jiangsu, Zhejiang, Anhui, Hunan and other places. In recent years, due to the related policies and strategies such as "moving silkworms from east to west", the center of silkworm breeding has gradually transferred to the west. As for the quality evaluation and harvesting and processing of mulberry medicinal materials, Most of the ancient and modern records of Mori Folium are the same. They are harvested after frost, and dried after removing impurities. The quality is better when the leaves are large and thick, yellowish green, holding prickly hands and undergoing frost. The harvesting period of Mori Cortex is slightly different in ancient and modern records. Ancient books record that it can be harvested all the year round, but in modern times, it is mostly harvested from late autumn to the next spring. The processing methods include removing soil and fibrous roots, scraping off yellow-brown rough skin, peeling off white skin and drying in the sun. The quality is better when they are white, thick, flexible, free of rough skin and full of powder. There are few records about the collection, processing and quality evaluation of Mori Ramulus and Mori Fructus in ancient Chinese herbal books. According to modern literature, Mori Ramulus is usually collected in late spring and early summer, with leaves removed, slightly dried, sliced while fresh, and dried in the sun. The best quality of Mori Ramulus is fine and tender with the yellow and white section. Mori Fructus is harvested from April to June when the fruit turns red, and dried in the sun, or slightly steamed and dried in the sun, and it is better to be big, dark purple, oily and thick. There are many processing methods of mulberry medicinal materials. Ancient books record stir frying, baking, burning and steaming of Mori Folium, in modern times, there is honey-roasted method, but most of them are used as raw products. In ancient materia medica, Mori Cortex has firing method, baking method, stir-frying method, honey-fried method, etc. In modern times, there are stir-fried and honey-fried methods, and most of them are used as raw products. Ancient books record that Mori Ramulus has cutting and frying methods, while modern ones have cutting, frying, wine-processed and bran-processed methods. Processing methods of Mori Fructus are consistent in ancient and modern times, and they are mostly dried after being cleaned or steamed. Based on the research results, it is suggested that M. alba should be selected as mulberry medicinal materials in the famous classical formulas, and appropriate medicinal parts and processing methods can be selected according to the indications of the famous classical formulas.
8.Herbal Textual Research on Menthae Haplocalycis Herba in Famous Classical Formulas
Hui JIANG ; Tian-yue LIAO ; Jing-qiong WAN ; Jin XU ; Wen-min DU ; Zhi-lai ZHAN ; Zhen OUYANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(10):150-158
In this paper, the name, origin, producing area and other aspects of Menthae Haplocalycis Herba in the famous classical formulas were carried out by consulting herbal literature, medical books, prescription books in the past dynasties and related modern documents. Through the textual research, it can be seen that the name of Bohe was used as the correct name in the mainstream of the past dynasties, and there were still multiple synonyms, most of which originated from the false transmission of dialectal accent, producing area and efficacy. There are many varieties recorded in the literature of the past dynasties such as Bohe, Longnao Bohe, Hubohe and Shibohe. According to the textual research, Bohe, Longnao Bohe and Yebohe are consistent with Mentha haplocalyx, whcih is the mainstream variety. Longnao Bohe is named for its form of producing area, Shibohe is Mosla chinensis, Daye Bohe is Agastache rugosa, and Nanbohe is M. crispata. Menthae Haplocalycis Herba has been widely planted since Tang dynasty. It was mainly grown in Jiangsu, Zhejiang, Jiangxi and Sichuan in Ming and Qing dynasties, and Jiangsu is the genuine production area. Its quality is best if it has dry body, no roots, many leaves, green color and strong smell. In ancient times, the stems and leaves of Menthae Haplocalycis Herba were often picked and dried in summer and autumn, which is basically the same as the records of modern times when the stems and leaves are luxuriant in summer and autumn, or when the flowers bloom to three rounds, they are picked in sunny days and cut in different times, and then dried in the sun or in the shade, and the raw products was often used as medicine in ancient and modern times. Before the Song dynasty, Menthae Haplocalycis Herba was recorded as pungent and warm. Until the Song dynasty, it was written as “extremely cool” in Lyuchanyan Bencao. It may have been thought in the early stage that it was similar to several warm herbs, such as Perilla frutescens, Stachys japonica, Elsholtzia ciliata and M. chinensis in appearance, all of which have the function of Xinsan, so it was recorded as warm. Since the Qing dynasty, Menthae Haplocalycis Herba has been recorded as cool property in the mainstream materia medica, Menthae Haplocalycis Herba recorded as pungent and cool in the 2020 edition of Chinese Pharmacopoeia, and its effect is to dissipate wind heat, clear the head, relieve the pharynx and so on, the records of efficacy in ancient and modern times are basically the same. Based on the research results, it is suggested that raw products of M. haplocalyx should be selected when developing the famous classical formulas containing Menthae Haplocalycis Herba.
9.Clinical features of intestinal polyps and risk factors for secondary intussusception in children: an analysis of 2 669 cases.
Can-Lin LI ; Yan-Hong LUO ; Hong-Juan OUYANG ; Li LIU ; Wen-Ting ZHANG ; Na JIANG ; Jia-Qi DUAN ; Mei-Zheng ZHAN ; Cheng-Xi LIU ; Jie-Yu YOU ; Yong LI ; Hong-Mei ZHAO
Chinese Journal of Contemporary Pediatrics 2022;24(5):530-535
OBJECTIVES:
To study the clinical features of intestinal polyps and the risk factors for secondary intussusception in children.
METHODS:
A retrospective analysis was performed for the medical data of 2 669 children with intestinal polyps. According to the presence or absence of secondary intussusception, they were divided into two groups: intussusception (n=346) and non-intussusception (n=2 323). Related medical data were compared between the two groups. The multivariate logistic regression analysis was used to identify the risk factors for secondary intussusception.
RESULTS:
Among the children with intestinal polyps, 62.42% were preschool children, and the male/female ratio was 2.08∶1; 92.66% had hematochezia as disease onset, and 94.34% had left colonic polyps and rectal polyps. There were 346 cases of secondary intussusception, with an incidence rate of 12.96% (346/2 669). Large polyps (OR=1.644, P<0.001), multiple polyps (≥2) (OR=6.034, P<0.001), and lobulated polyps (OR=93.801, P<0.001) were the risk factors for secondary intussusception.
CONCLUSIONS
Intestinal polyps in children often occur in preschool age, mostly in boys, and most of the children have hematochezia as disease onset, with the predilection sites of the left colon and the rectum. Larger polyps, multiple polyps, and lobulated polyps may increase the risk of secondary intussusception, and endoscopic intervention is needed as early as possible to improve prognosis.
Child, Preschool
;
Female
;
Gastrointestinal Hemorrhage
;
Humans
;
Intestinal Polyps/complications*
;
Intussusception/complications*
;
Male
;
Retrospective Studies
;
Risk Factors
10. Expert consensus on prevention and cardiopulmonary resuscitation for cardiac arrest in COVID-19
Wei SONG ; Yanhong OUYANG ; Yuanshui LIU ; Heping XU ; Feng ZHAN ; Wenteng CHEN ; Jun ZHANG ; Shengyang YI ; Jie WEI ; Xiangdong JIAN ; Deren WANG ; Xianjin DU ; Ying CHEN ; Yingqi ZHANG ; Shuming XIANYU ; Qiong NING ; Xiang LI ; Xiaotong HAN ; Yan CAO ; Tao YU ; Wenwei CAI ; Sheng'Ang ZHOU ; Yu CAO ; Xiaobei CHEN ; Shunjiang XU ; Zong'An LIANG ; Duohu WU ; Fen AI ; Zhong WANG ; Qingyi MENG ; Yuhong MI ; Sisen ZHANG ; Rongjia YANG ; Shouchun YAN ; Wenbin HAN ; Yong LIN ; Chuanyun QIAN ; Wenwu ZHANG ; Yan XIONG ; Jun LV ; Baochi LIU ; Xiaojun HE ; Xuelian SUN ; Yufang CAO ; Tian'En ZHOU
Asian Pacific Journal of Tropical Medicine 2021;14(6):241-253
Background: Cardiopulmonary resuscitation (CPR) strategies in COVID-19 patients differ from those in patients suffering from cardiogenic cardiac arrest. During CPR, both healthcare and non-healthcare workers who provide resuscitation are at risk of infection. The Working Group for Expert Consensus on Prevention and Cardiopulmonary Resuscitation for Cardiac Arrest in COVID-19 has developed this Chinese Expert Consensus to guide clinical practice of CPR in COVID-19 patients. Main recommendations: 1) A medical team should be assigned to evaluate severe and critical COVID-19 for early monitoring of cardiac-arrest warning signs. 2) Psychological counseling and treatment are highly recommended, since sympathetic and vagal abnormalities induced by psychological stress from the COVID-19 pandemic can induce cardiac arrest. 3) Healthcare workers should wear personal protective equipment (PPE). 4) Mouth-to-mouth ventilation should be avoided on patients suspected of having or diagnosed with COVID-19. 5) Hands-only chest compression and mechanical chest compression are recommended. 6) Tracheal-intubation procedures should be optimized and tracheal-intubation strategies should be implemented early. 7) CPR should be provided for 20-30 min. 8) Various factors should be taken into consideration such as the interests of patients and family members, ethics, transmission risks, and laws and regulations governing infectious disease control. Changes in management: The following changes or modifications to CPR strategy in COVID-19 patients are proposed: 1) Healthcare workers should wear PPE. 2) Hands-only chest compression and mechanical chest compression can be implemented to reduce or avoid the spread of viruses by aerosols. 3) Both the benefits to patients and the risk of infection should be considered. 4) Hhealthcare workers should be fully aware of and trained in CPR strategies and procedures specifically for patients with COVID-19.

Result Analysis
Print
Save
E-mail