1.Mechanism of Yantiao Prescription in Treating Lipopolysaccharide-induced Acute Lung Injury Based on Arachidonic Acid Metabolic Pathways
Pengcheng LI ; Tianyang CHEN ; Rong FANG ; Anna ZHANG ; Sijia WU ; Wei LIU ; Qian WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):101-110
ObjectiveTo clarify the anti-inflammatory and lung-protective effects of Yantiao prescription on lipopolysaccharide (LPS)-induced acute lung injury (ALI), and to explore the impact of Yantiao prescription on the metabolic pathways of arachidonic acid (AA) in vivo. MethodsThirty male C57BL/6J mice were randomly divided into the following groups based on body weight: normal group, model group, dexamethasone group (2 mg·kg-1), low-dose Yantiao prescription group (18 g·kg-1), and high-dose Yantiao prescription group (36 g·kg-1), with 6 mice in each group. The ALI mouse model was established by intraperitoneal injection of LPS. The treatment groups received oral gavage once a day for 7 consecutive days, and serum and lung tissue were collected at the end of the experiment. The content of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in serum was detected by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to assess lung tissue pathology. The wet/dry weight ratio (W/D) and myeloperoxidase (MPO) activity in lung tissue were measured. The content of AA metabolites in serum and lung tissue was measured by liquid chromatography triple quadrupole-mass spectrometry (LC-MS/MS). ResultsCompared with the conditions in the normal group, the content of serum pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in the model group was significantly increased (P<0.01). The alveolar structure in mice was severely damaged, with markedly thickened alveolar walls and extensive inflammatory cell infiltration. The W/D ratio and MPO activity in lung tissue were significantly increased (P<0.01). The content of AA metabolites, including prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), 11(S)-hydroxy-eicosatetraenoic acid [11(S)-HETE], and 5-hydroxy-eicosatetraenoic acid (5-HETE) in serum and lung tissue was significantly increased (P<0.05), while the content of 11,12-epoxyeicosatrienoic acid (11,12-EET) and 14,15-epoxyeicosatrienoic acid (14,15-EET) in serum was significantly decreased (P<0.01). Compared with the results in the model group, the content of serum pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in the dexamethasone group, low-dose Yantiao prescription group, and high-dose Yantiao prescription group was significantly reduced (P<0.05). Mild thickening of alveolar walls, scattered inflammatory cell infiltration, and relatively intact tissue structure with improved alveolar architecture were observed. The W/D ratio and MPO activity in lung tissue were significantly reduced (P<0.01). The content of AA metabolites PGD2, PGE2, 11(S)-HETE, and 5-HETE in serum from the dexamethasone group was significantly decreased (P<0.05), while the content of 14,15-EET in serum significantly increased (P<0.01), and the content of 5-HETE in lung tissue significantly decreased (P<0.01). In the low-dose and high-dose Yantiao prescription groups, the content of AA metabolites PGD2, PGE2, 11(S)-HETE, and 5-HETE in serum and lung tissue was significantly decreased (P<0.05), while the content of 11,12-EET in both serum and lung tissue was significantly increased (P<0.05). ConclusionYantiao prescription has significant protective effects against LPS-induced ALI, which are related to its regulation of AA metabolic pathways in vivo.
2.Protein palmitoylation: A potential therapeutic target in cardiovascular diseases.
Sijia ZHAO ; Yanyan YANG ; Hong LI ; Pin SUN ; Xiangqin HE ; Chao WANG ; Jingjing ZHANG ; Yu TIAN ; Tao YU ; Zhirong JIANG
Acta Pharmaceutica Sinica B 2025;15(10):5127-5144
Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.
3.High glucose induces hippocampal neuron impairment through the SKP1/COX7C pathway: A potential mechanism for perimenopausal depression.
Ziqi WANG ; Zhiyuan LIU ; Sijia FENG ; Xintong SONG ; Dequan LIU ; Ning MA ; Xinyue ZHANG ; Weiwei LIU ; Dan Ohtan WANG ; Xiaoling LIU ; Takashi IKEJIMA
Acta Pharmaceutica Sinica B 2025;15(11):5832-5853
Perimenopause raises the risk and incidence of depression, whereas the underlying molecular mechanism remains unclear. Disturbed glucose regulation has been widely documented in depressive disorders, which renders the brain susceptible to various stresses such as estrogen depletion. However, whether and how glucose dysfunction regulates depression-like behaviors and neuronal damage in perimenopausal transition remains unexplored. Here, a prominent depressive phenotype was found in perimenopausal mice induced by the ovarian toxin 4-vinylcyclohexene diepoxide (VCD). The VCD depression susceptible group (VCDSS) and the VCD depression resilient group (VCDRES) were determined using a ROC-based behavioral screening approach. We found that the hippocampus, a crucial region linked to depression, had hyperglycemia and mitochondrial abnormalities. Interestingly, oral administration of the SGLT2 inhibitor empagliflozin (EMPA) and intrahippocampal glucose infusion suggest a close relationship between hyperglycemia in the hippocampus and the susceptibility to depression. We verified that cytochrome c oxidase 7c (COX7C) downregulation is a potential cause of the high glucose-induced neuronal injury using proteomic screening and biochemical validations. High glucose causes COX7C to be ubiquitinated in a S-phase kinase associated protein 1 (SKP1)-dependent manner. According to these results, SKP1/COX7C represents a unique therapeutic target and a novel molecular route for treating perimenopausal depression.
4.Contamination risk and drug resistance analysis of Klebsiella pneumoniae in a medical institution in Minghang District, Shanghai, 2021‒2023
Sijia ZHANG ; Xing ZHANG ; Liang TIAN ; Yibin ZHOU ; Xiaosa WEN ; Jing WANG ; Zhiyin XU ; Min WU
Shanghai Journal of Preventive Medicine 2025;37(4):289-295
ObjectiveTo investigate the contamination status, transmission risk and drug resistance of Klebsiella pneumoniae (KP) on the object surfaces in the surrounding environment of hospitalized patients infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) , so as to provide a scientific guidance for the prevention and control of healthcare-associated infection. MethodsSamples from the surfaces of objects in the surrounding environment of CRKP infected patients living in the intensive care unit (ICU) and hand specimens from healthcare workers were collected for KP isolation and identification, as well as drug susceptible test in a medical institution located in Minhang District, Shanghai from 2021 to 2023. Additionally, both univariate and multivariate logistic regression analyses were used to identify the influencing factors associated with KP contamination in the hospital environment. ResultsA total of 546 surface samples were collected from the surrounding environment objects of 15 patients infected with CRKP, with a KP detection rate of 6.59% (36/546).The KP detection rate in the ICU of general ward (10.22%) was higher than that in the ICU of emergency department (2.94%) (χ2=12.142, P<0.001). Moreover, the KP detection rate on the surfaces of patient-contacted items (15.66%) was higher than that on shared-use items (6.25%), cleaning items (10.00%), and medical supplies (3.30%) (χ2=17.943, P<0.001). Besides, the detection rate of KP in items sent out of hospital for disinfection (15.38%) was higher than that in those self-disinfected (4.20%) (χ2=19.996, P<0.001).The highest detection rate of KP was observed in high-temperature washing (15.13%, 18/119) (χ2=21.219, P<0.001), while the lowest detection rate was observed in antibacterial hand sanitizer with trichlorohydroxydiphenyl ether sanitizing factor (0, 0/60) ( χ2=21.219, P<0.001).The detection rate of KP in samples taken more than 24 hours after the last disinfection (23.08%) was higher than that in those taken at 4 to24 hours (12.90%) and less than 4 hours (4.22%) (χ2=23.398,P<0.001).ICU of general ward (OR=4.045, 95%CI: 2.206‒7.416), patient-contacted items (OR=3.113, 95%CI: 1.191‒8.141), and self-disinfection ( OR=0.241, 95%CI:0.144‒0.402) were influencing factors for KP contamination in environmental surface. From 2021 to 2023, the drug resistance rates of hospital environmental KP isolates showed an upward trend (P<0.001) to antibiotics such as ceftazidime and gentamicin. Furthermore, high drug resistance rates of KP (>90%) were observed to ciprofloxacin, levofloxacin, cefotaxime, ceftriaxone, and cefepime. ConclusionCRKP can be transmitted outward through the surfaces of objects in the patients’ surroundings, and the drug resistance situation is severe. In clinical settings, it is necessary to implement isolation measures for CRKP infection patients, to increase the frequency of disinfection for objects in their surroundings, to strengthen hand hygiene practices, and to use antibiotics appropriately.
5.Metabolome and transcriptome association study reveals biosynthesis of specialized benzylisoquinoline alkaloids in Phellodendron amurense.
Tingxia LIU ; Wanran ZHANG ; Sijia WANG ; Ya TIAN ; Yifan WANG ; Ranran GAO ; Shilin CHEN ; Wei SUN ; Wei MA ; Zhichao XU
Chinese Herbal Medicines 2025;17(1):178-188
OBJECTIVE:
Benzylisoquinoline alkaloids (BIAs) have pharmacological functions and clinical use. BIAs are mainly distributed in plant species across the order Ranunculales and the genus Phellodendron from Sapindales. The BIA biosynthesis has been intensively investigated in Ranunculales species. However, the accumulation mechanism of BIAs in Phellodendron is largely unknown. The aim of this study is to unravel the biosynthetic pathways of BIAs in Phellodendron amurens.
METHODS:
The transcriptome and metabolome data from 18 different tissues of P. amurense were meticulously sequenced and subsequently subjected to a thorough analysis. Weighted gene co-expression network analysis (WGCNA), a powerful systems biology approach that facilitates the construction and subsequent analysis of co-expression networks, was utilized to identify candidate genes involved in BIAs biosynthesis. Following this, recombinant plasmids containing candidate genes were expressed in Escherichia coli, a widely used prokaryotic expression system. The purpose of this genetic engineering endeavor was to express the candidate genes within the bacteria, thereby enabling the assessment of the resultant enzyme activity.
RESULTS:
The synonymous substitutions per synonymous site for paralogs indicated that at least one whole genome duplication event has occurred. The potential BIA biosynthetic pathway of P. amurense was proposed, and two PR10/Bet v1 members, 14 CYP450s, and 33 methyltransferases were selected as related to BIA biosynthesis. One PR10/Bet v1 was identified as norcoclaurine synthase, which could catalyze dopamine and 4-hydroxyphenylacetaldehyde into (S)-norcoclaurine.
CONCLUSION
Our studies provide important insights into the biosynthesis and evolution of BIAs in non-Ranunculales species.
6.Aspiration after dysphasia in recent twenty years:a visualized analysis
Longxian HUANG ; Yan ZUO ; Limei CHEN ; Sijia GU ; Jinmei JIANG ; Zhiwei ZHANG
Chinese Journal of Rehabilitation Theory and Practice 2024;30(3):292-302
Objective To analyze the current status,hot spots and trends of Chinese and English researches in the field of aspiration after dysphasia in the past twenty years. Methods The articles about aspiration after dysphasia were retrieved from CNKI and Web of Science(WOS)core collec-tion database,from January,2003 to June,2023,and were analyzed with CiteSpace 6.1.R6. Results A total of 3 231 articles were included.The annual articles were published more and more year by year.The most English literatures came from the United States.Hot spots mainly focused on the assessment of dysphasia,prevention of complication,nutrition and rehabilitation therapy.It would concentrate on the application of the volume-viscosity swallow test and assessment scales,rehabilitation,penetration aspiration,outcome and effect validation,quality of life,feeding and nutrition condition,and evidence-based nursing,etc.,in the future. Conclusion The researches in the field of aspiration after dysphasia have been increasing in recent years,and the themes and contents of researches have been deepening.
7.Functional study on elastase regulation of inflammatory neutrophils recruitment
Yang LIU ; Ling MENG ; Sijia FAN ; Chunguang REN ; Huan ZHANG
Chinese Journal of Immunology 2024;40(3):449-455
Objective:To explore the effect of neutrophil elastase(NE)on neutrophil inflammatory recruitment.Methods:Mice bone marrow-derived neutrophils were pretreated with an exogenous elastase inhibitor-sivelestat sodium.The effects of elastase inhibition on the in vivo inflammatory recruitment,chemotaxis,adhesion,cell polarization and spreading of NE were examined by peritonitis adoptive transfer assay,dunn chamber,flow chamber,immunofluorescence staining and spreading assay,respectively.The effects of elastase inhibition on NE phagocytosis and reactive oxygen species(ROS)release capacity were detected by flow cytom-etry and the luminol chemiluminescence system.Results:Sivelestat sodium pretreatment significantly attenuated neutrophil in vivo in-flammatory recruitment(P<0.001);impaired neutrophil perception of chemotaxis in vitro(P<0.05),slowed chemotactic velocity(P<0.05),and decreased the chemotactic distance(P<0.05);reduced the adhesion of neutrophils to inflamed endothelial cells(P<0.000 1)and inhibited the phagocytosis of bacteria by neutrophils(P<0.01);however,there was no significant effect on neutrophil spreading,polarization and ROS.Conclusion:NE inhibition significantly impaired the inflammatory recruitment cascade response and phagocyto-sis of neutrophils in vitro and in vivo but had no significant effect on the spreading,polarization and ROS release of neutrophils.
8.Differential expression of inflammatory proteins in diabetic skin ulcers and ordinary skin ulcers
Wu XIONG ; Youyuan HE ; Xi ZHANG ; Jianda ZHOU ; Jia CHEN ; Xiaoling ZOU ; Sijia ZHAO ; Xingxing ZHONG ; Yutan CAO ; Wenjing QU
Journal of Chinese Physician 2024;26(3):331-336
Objective:To study and screen the differential expression of inflammatory proteins in diabetes skin ulcers and common skin ulcers, so as to provide experimental basis for further research on anti-inflammatory and healing drug targets of diabetes skin ulcers.Methods:The tissues of 11 patients with diabetes skin ulcer, 12 patients with common skin ulcer and 11 patients with normal skin were collected from the First Hospital of Hunan University of Chinese Medicine. The levels of inflammatory protein Toll like receptor 4 (TLR4), nuclear factor κB (NF-κB), pro-inflammatory factor interferon -γ (IFN -γ), tumor necrosis factor - α (TNF -α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1β (IL-1β), macrophage chemotactic protein-1 (MCP-1), anti-inflammatory factors epidermal growth factor (EGF), interleukin-4 (IL-4), and interleukin-10 (IL-10) were detected in three groups of tissues using enzyme-linked immunosorbent assay (ELISA).Results:Compared with normal tissues, the concentrations of TLR4, NF-κB, IFN -γ, TNF -α, IL-1β, IL-6, IL-8, MCP-1 and EGF in common ulcer skin tissues and diabetes ulcer tissues were higher, and the concentrations of IL-10 were lower, with statistically significant differences (all P<0.05); Compared with the normal tissue, the concentration of IL-4 in diabetes ulcer tissue was lower, the difference was statistically significant ( P<0.05); Compared with ordinary ulcer skin tissue, the concentrations of TLR4, NF-κB and MCP-1 in diabetes ulcer tissue were higher, and the concentrations of IL-4 were lower, with statistically significant differences (all P<0.05). Conclusions:The skin ulcer in diabetes patients will have inflammatory reaction, and high glucose promotes the inflammatory reaction of skin ulcer, which may be related to the abnormal expression of TLR4, NF-κB, MCP-1 and IL-4. TLR4/NF-κB signal pathway and inflammatory factors MCP-1 and IL-4 may be the target of the inflammation regulation of diabetes skin ulcer.
9.TCM Pharmacology Based on Bibliometrics and Patent Analysis: A Case Study of Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences
Lin ZHANG ; Yuhan DENG ; Yanwen LI ; Luming QIU ; Sijia MA ; Tuo LIU ; Zhiyong LI ; Yujie LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):8-18
ObjectiveTo analyze the literature related to traditional Chinese medicine (TCM) pharmacology of Institute of Chinese Materia and Medica, China Academy of Chinese Medical Sciences (hereinafter referred to as "Institute of Chinese Materia and Medica"), and evaluate the research status, development trend, influence of discipline members, and patent technology of this field. MethodThe papers from 2002 to 2024 in the databases of CNKI and Web of Science (WOS) were searched, whose first authors or corresponding authors are from the Institute of Chinese Materia and Medica, and CiteSpace 6.3.R6 was adopted for visual analysis of the annual number of publications and keywords. Additionally, the total number of published papers, citation times, and other measurement parameters of discipline members of TCM pharmacology in the institute were counted. After obtaining the h index, the academic track was calculated, and the academic influence of discipline members was quantitatively evaluated from the aspects of the academic track T and highly cited papers. Meanwhile, patent data from 2005 to 2024 of TCM pharmacology in the studied institute were retrieved from the HimmPat patent database, and Excel 2022 and Origin 2021 were utilized to conduct visual analysis on the overall patent application trend and technology composition. ResultIn the past 20 years or more, the annual publication of academic papers has been on the rise generally, and the key words include "animal model", "mechanism of action", "network pharmacology" and so on. The studies focus on the innovative methods of TCM pharmacological mechanisms, basic research on TCM prevention and treatment of major non-infectious diseases, and the prevention and treatment of respiratory viral diseases. The academic track T of the discipline members of TCM pharmacology in the Institute of Chinese Materia and Medica is positive, with sound personal influence. In recent years, the patent application trend has increased significantly, mainly concentrating on A61K patents and G01N subcategories, and IPC large-group analysis shows that the main technical applications are mainly in A61K36, A61K31, and other fields. ConclusionTCM pharmacology in the institute develops steadily and the academic influence of the discipline members is still sound, with fruitful patent achievements. In the future, research on pharmacological discipline innovation and new drug research and development can be enhanced, and multidisciplinary integration studies should be carried out to promote TCM modernization.
10.Analysis of the current situation and related factors of the knowledge, behavior and educational attitude of sexual abuse prevention among primary school students in Luzhou City
LI Mao, CHEN Xiaoxue, YANG Wenxiu, XU Sijia, LIAO Maoxu, ZHANG Rong, YE Yunli
Chinese Journal of School Health 2024;45(11):1536-1540
Objective:
To assess the current situation and related factors of the knowledge, attitude and behavior toward sexual abuse prevention among primary school students in Luzhou City, Sichuan Province, so as to provide a reference basis for the development of sexual abuse prevention education for primary school students.
Methods:
A total of 4 563 primary school students in Luzhou City were sampled from December 2023 to January 2024 by stratified cluster sampling, and self administered questionnaires were conducted. The binary Logistic regression analysis was used to analyze related factors of the knowledge, attitude and behavior toward sexual abuse prevention.
Results:
The qualified rates of knowledge, behavior and attitude among primary school students towards sexual abuse prevention in Luzhou were 76.2%, 21.3%, and 90.2 %, respectively. The binary Logistic regression showed that males ( OR=0.66, 95%CI =0.56-0.78), attending rural schools ( OR=0.77, 95%CI =0.64-0.92), left behind status ( OR=0.66, 95%CI =0.53-0.81), and household registration in Lu County ( OR=0.57, 95%CI =0.46-0.70) and Gulin County ( OR=0.70, 95%CI =0.57-0.86) had lower qualified rates of the knowledge of sexual abuse prevention among primary school students ( P < 0.05 ); while qualified knowledge of sexual abuse prevention was positively associated with grade ( OR =3.05-18.81); attending rural schools ( OR=0.82, 95%CI =0.70-0.95) and not having received education on prevention of sexual abuse ( OR=0.55, 95%CI = 0.47-0.64) had lower qualified rates of the behavior of sexual abuse prevention among primary school students ( P <0.05); household registration in Lu County ( OR=0.73, 95%CI =0.58-0.92) and not having received education on prevention of sexual abuse ( OR=0.33, 95%CI =0.26-0.40) had lower qualified rates of the educational attitudes of sexual abuse prevention among primary school students ( P <0.05).
Conclusions
The qualified rates of knowledge and behavior of sexual abuse prevention among primary school students in Luzhou City needs to be improved. Health education regarding sexual abuse prevention might help enhance primary school students awareness and skills of sexual abuse prevention.


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