1.The effect of rutaecarpine on improving fatty liver and osteoporosis in MAFLD mice
Yu-hao ZHANG ; Yi-ning LI ; Xin-hai JIANG ; Wei-zhi WANG ; Shun-wang LI ; Ren SHENG ; Li-juan LEI ; Yu-yan ZHANG ; Jing-rui WANG ; Xin-wei WEI ; Yan-ni XU ; Yan LIN ; Lin TANG ; Shu-yi SI
Acta Pharmaceutica Sinica 2025;60(1):141-149
Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg-1) and a high dose (15 mg·kg-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D303)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.
2.Anthocyanins alleviate pentatetrazene-induced epileptic seizures in rats by inhibiting cuproptosis
Rui NING ; Xiangwei ZHANG ; Shuhua WU ; Zhongbo HU ; Jiangtao PENG ; Ke GUO ; Jianmin LI
Chinese Journal of Neuroanatomy 2025;41(5):625-634
Objective:To study the effect of anthocyanins(C3G)on cuproptosis in chronic epileptic rats.Methods:Chronic epileptic rat model was induced by pentatetrazol(PTZ),and 90 SD rats were randomly divided into control group,PTZ group,elesclomol(ELC)group,tetrathiomolybdate(TTM)group,C3G group and ELC+C3G group.The grade,latency and frequency of seizures were recorded in each group.electroencephalogram(EEG)was used to detect abnormal electrical discharge in the brain.The action potential of hippocampal neurons was measured by patch-clamp technique.The contents of glutathione(GSH)and cuprous ions(Cu+)in hippocampus were determined by kit.Neuron damage in hippocampus was evaluated by Nissl staining.The expression of ferredoxin1(FDX1)and lipoic acid synthase(LIAS)in hippocampus was analyzed by immunohistochemistry and Western blot.Results:Compared with the control group,the rats in the PTZ group exhibited epileptic-like seizures,suggesting that the modeling was successful.Com-pared with other epileptic groups,the ELC group showed increased seizure grade,more abnormal discharges,shortened latency period,enhanced neuronal excitability,decreased Nissl particles,elevated Cu+levels,decreased GSH levels,and increased expressions of FDX1 and LIAS.The reverse was observed in C3G group(P<0.05).Neuron damage in ELC+C3G group was less severe than that in ELC group,but more than that in PTZ group(P<0.05).Neuron dam-age in TTM group was less severe than that in PTZ group,but more severe than that in C3G group(P<0.05).Conclusion:cuproptosis exists in hippocampus of rats with chronic epilepsy,and the C3G can significantly inhibit cu-proptosis and alleviate the occurrence and development of chronic epilepsy.
3.Study on the Characteristics of TCM Syndromes of Insomnia Based on Multiple Data Analysis Methods
Xianbei WANG ; Rui ZHANG ; Jiwei ZHANG ; Yuying XU ; Ning SUN ; Miaoran WANG ; Xiaoning TAN ; Yufei WU ; Zirong LI ; Jing CAO ; Taiwei LOU ; Rui WEI ; Hongjin DU ; Qiuyan LI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(5):25-31
Objective To explore the distribution of common TCM syndromes and symptoms of insomnia;To prepare for the construction of the theoretical framework and item pool of syndrome diagnosis and efficacy evaluation scale.Methods TCM guideline standards of insomnia,textbooks and journals over the years were retrieved,the information of TCM syndromes,syndrome elements and symptoms was extracted,the guideline textbook and journal database were established,and descriptive statistics,association rules,systematic clustering,factor analysis,potential categories and implicit structure analysis were carried out.Results Totally 116 guide standards and textbooks over the years were included,and 454 articles of journals were included.The high-frequency symptoms accounted for≥3%of the guide textbooks and journal databases were 87 and 79 categories,respectively,and the cumulative proportion was 87.48%and 87.75%,respectively.According to the analysis results,five common TCM syndromes and their characteristic symptom classification of insomnia were finally deduced.According to the frequency/person time distribution,they were heart and spleen deficiency syndrome,yin deficiency and fire hyperactivity syndrome,liver fire disturbing heart syndrome,phlegm heat disturbing heart syndrome,heart and gallbladder qi deficiency syndrome.Conclusion There are five common TCM syndromes of insomnia,and the characteristic symptoms of each TCM syndrome provide a reference source for the theoretical framework of syndrome diagnosis and efficacy evaluation scale and the establishment of item pool.
4.Analysis on revision points of GB 19083-2023 Protective face mask for medical use
Xiao-xiao HE ; Xiong-yi HUANG ; Li YANG ; Ning-rui ZHANG ; Qing-hui REN ; He-hua ZHANG
Chinese Medical Equipment Journal 2025;46(1):73-77
The background of revising GB 19083-2023 Protective face mask for medical use was introduced.GB 19083-2023 was compared with GB 19083-2010 Technical requirements for protective face mask for medical use.The revision points were described in detail involving in dead space,total leakage rate,respiratory resistance,resistance to synthetic blood penetration,microbial indicators,biocompatibility and etc,and the convergence between GB 19083-2023 and international mainstream standards was analyzed.References were provided for the understanding of the standard for the production enterprises and consumers.[Chinese Medical Equipment Journal,2025,46(1):73-77]
5.Epidemiological characteristics of febrile seizure among children under 6 years old in Ningbo City from 2015 to 2021
Guangxu LIU ; Liang ZHANG ; Houyu ZHAO ; Siwei DENG ; Junting YANG ; Ning LI ; Rui MA ; Yan HE ; Guozhang XU ; Zhike LIU ; Siyan ZHAN
Journal of Peking University(Health Sciences) 2025;57(3):584-591
Objective:To describe the epidemiological characteristics and changes of febrile seizure(FS)among children under 6 years old in Ningbo City,Zhejiang Province from 2015 to 2021.Methods:Based on the Ningbo Regional Health Information Platform,a dynamic cohort was established using vacci-nation registration information,and the cases of FS were identified by the diagnostic results of Chinese terms or International Classification of Diseases 10th revision(ICD-10)R56.0 code in the electronic medical records.The first visit of FS during the observation period was defined as a new case,and a re-currence case was defined as the case with a visit interval of more than 7 days.The 95%confidence in-terval(CI)of FS incidence density was calculated by the Poisson distribution.Results:From January 2015 to June 2020,there were 1.3 million children under 6 years old in Ningbo,with male accounting for 52.87%.The median follow-up time was 2.83(1.55-4.00)years.During the follow-up period,12 776 new onset cases had FS,with more males than females,with an overall incidence density of 4.34(95%CI:4.27-4.40)/1 000 person-years and a recurrence rate of 21.63%.There was a higher inci-dence density in children who were male,born in Ningbo and of non-mobility.The incidence density of FS was higher in urban areas than in rural and rural-urban fringe areas,and the incidence density was different among districts and counties.The peak density was found in children aged 18-23 months[8.42(95%CI:8.11-8.74)/1 000 person-years].From 2015 to 2019,the incidence density in-creased with calendar year(Ptrend<0.001),and the highest was 5.62(95%CI:5.43-5.81)/1 000 person-years.The incidence density of FS decreased significantly during the period between 2020 and 2021.The incidence density was higher in winter.Conclusion:From 2015 to 2019,the overall inci-dence density of FS in children under 6 years old in Ningbo City presented an increasing trend.More at-tention should be paid to the health education,the improvement of the health maintenance model,the en-hancement of the cognition of FS,the identification and treatment of FS among high-risk population and regions so as to prevent its recurrence and reduce the disease burden during the corona virus disease 2019(COVID-19)epide-mic.
6.Research progress in anti-tuberculosis drug targets and novel therapeutic strategies
Yang ZHANG ; Ming-rui SUN ; Xiao-tian LI ; Ren FANG ; Jia-yin XING ; Ning-ning SONG
Chinese Journal of Zoonoses 2025;41(4):351-357
Tuberculosis(TB),a chronic infectious disease caused by infection with the Mycobacterium tuberculosis complex(MTBC),has re-emerged as the leading cause of death from a single infectious agent worldwide.Because of widespread use and mis-use of anti-tuberculosis drugs,the emergence of multidrug-resistant TB(MDR-TB)and extensively drug-resistant TB(XDR-TB)is increasing,thus posing a serious threat to global health.The current problem of drug resistance is a major prevention and treatment challenge;therefore,the search for new drug targets is urgently needed.In recent years,substantial progress has been made in re-search on anti-tuberculosis drug targets and novel therapeutic strategies.Herein,we summarize recent research progress in anti-tuberculosis drug targets,primarily cell wall synthesis,nucleic acid replication and transcription,and energy metabolism.We also provide an overview of research progress regarding two novel therapeutic strategies,to provide a theoretical basis and research ideas for the development of new clinical drugs.
7.Mechanism of ultrafine garlic powder in improving mouse atherosclerosis and dyslipidemia
Ning-ning SHAO ; Jian-ming YANG ; Yao-guang WANG ; Tao ZHANG ; Xiao-ming ZHAO ; Jin-rui DONG
Chinese Pharmacological Bulletin 2025;41(7):1376-1381
Aim To investigate the mechanism of ultra-fine garlic powder(UGP)in ameliorating dyslipidemia and aortic inflammation and fibrosis in atherosclerotic(AS)mice.Methods A 10-week ApoE-/-mouse AS model was constructed,cardiac index was meas-ured,and aortic histopathological changes were ob-served by oil red O staining.Serum inflammatory factor levels were detected by ELISA,and the expression of JNK,NF-κB,ERK and their phosphorylated proteins were detected by Western blot.Results Cardiac in-dex and other indicators as well as aortic lesions were worsened in the AS group,as compared with the normal control group.Compared with the AS group,the UGP treatment group and the traditional garlic grinding pow-der(TGP)treatment group significantly decreased total cholesterol(TC),triglyceride(TG),low-density lipo-protein cholesterol(LDL-C),atherosclerosis index(AI1,AI2),and coronary cardiac index and restored high-density lipoprotein cholesterol(HDL-C)levels,and the area of aortic lesions,inflammation and fibrosis were significantly improved,and at the same time,sig-nificantly inhibited the expression of TNF-α,IL-1β,and IL-6,as well as the expression of p-JNK,p-NF-κB and p-ERK proteins.The therapeutic effect of the UGP group was superior to that of the TGP group.Conclu-sion UGP can significantly inhibit the formation of aortic endothelial AS plaques,reduce the levels of in-flammation and fibrosis,and regulate blood lipids in a-orta of AS mice.
8.Role of CHMP4C in gastric cancer development through regulating necroptosis and its action mechanism
Qi-ning GUO ; Ya-ping LI ; Li PEI ; Long-chen YU ; Zheng-dong LUO ; Rui ZHAO ; Zhong-fang NIU ; Xin ZHANG
Chinese Journal of Current Advances in General Surgery 2025;28(2):125-133
Objective:Exploring the role and mechanism of CHMP4C in regulating necroptosis during gastric can-cer development and progression.Method:The expression of CHMP4C in pan-cancer was analyzed by bioinformatics methods,and the expression of CHMP4C was detected in human normal gastric epithelial cells and GC cell lines by RT-qPCR and Western blot.Overexpression or knockdown of CHMP4C was performed in GC cell lines,and the effects of CHMP4C on the growth and proliferation of GC cells were detected using CCK-8 and clone formation assays.The CCK-8 experiment and Hoechst/PI double staining experiment were used to detect the changes in GC cell mortality and PI positive cell ratio after treatment with the necroptsis inducer TSZ or inhibitor necrostatin-1(Nec-1).Western blot assay was used to detect the protein and phosphorylation levels of RIPK1,RIPK3,and MLKL in GC cells.Result:CHMP4C was upregulated in GC tissues and cells.The CCK-8 and clone formation experiments showed that overex-pression of CHMP4C significantly improved the proliferation ability and colony formation efficiency of GC cells,while knockdown of CHMP4C significantly weakened GC cells.Moreover,the results of CCK-8 and Hoechst 33342/PI double staining experiments showed that upregulated CHMP4C could inhibit TSZ induced GC cell death;Nec-1 can reverse the decrease in GC cell viability caused by CHMP4C knockdown.Western blot experiment showed that the levels of p-RIPK1,p-RIPK3,and p-MLKL were significantly decreased in overexpressing cells,while they were increased in knockdown cells.After treatment with Nec-1,the expression levels of these three proteins decreased in knockdown cells.Conclusion:CHMP4C may promote GC progression by negatively regulating necroptosis through inhibiting the phosphorylation of the RIPK1/RIPK3/MLKL signaling pathway,suggesting that it is expected to be a potential target for GC therapy.
9.Analysis of neuromedin U remodeling the metabolic microenvironment of pancreatic tumors through Hedgehog signaling pathway
Yuchang WANG ; Yidan ZHANG ; Tianjiao HU ; Mingjia GAO ; Ning HAN ; Jiani ZHANG ; Rui ZHENG
Cancer Research and Clinic 2025;37(6):422-428
Objective:To construct an in situ pancreatic tumor model in mice and explore the mechanism of neuromedin U (NMU) remodeling the metabolic microenvironment of pancreatic tumors via the Hedgehog signaling pathway.Methods:C57BL/6 NMU -/- heterozygous mice were bred in one cage with a female-to-male ratio of 2:1. The tail tissues of offspring rats were taken, and knockout primers were designed according to the sequence structure of NMU gene. The C57BL/6 NMU -/- mouse genotypes were identified by polymerase chain reaction (PCR) and agarose gel electrophoresis. Five C57BL/6 NMU -/- homozygotes and five wild type mice aged 8 to 9 weeks were selected, and Panc02 cell suspension of pancreatic cancer in logarithmic growth phase was injected into pancreatic tail tissue to construct tumor bearing mice model of pancreatic tumor in situ. After 3 weeks of tumor loading, flow cytometry was used to detect the abundance changes of CD8 + T cells in the spleen tissues of two groups of mice. GSE102238 (data published in August 2017) and GSE62452 (data published in July 2016) datasets were download from the Gene Expression Omnibus (GEO) database, including 119 samples of pancreatic cancer tissue and 111 samples of normal pancreatic tissue adjacent to cancer, and the differential expression factors of the two groups of samples were screened. R language limma package was used to analyze the differential expression of NMU mRNA in pancreatic cancer tissues and adjacent normal tissues; the relative expression level of NMU mRNA in pancreatic cancer patients of different ages and tumor grades was analyzed by ggpubr package. The relative expression level data of NMU mRNA in pancreatic tumor patients were extracted, and the patients were divided into high expression group (>2.48) and low expression group (<2.48) based on the median value (2.48). The CIBERSORT algorithm was used to calculate the difference in the content of infiltrating immune cells in pancreatic tumors between the two groups of patients. The overall survival of patients with different relative expression levels of NMU mRNA in the OncoLnc database (59 cases in the high expression group and 59 cases in the low expression group) was compared. The data of 178 patients with pancreatic cancer in TCGA-PAAD of The Cancer Genome Atlas (TCGA) database (updated in March 2024) were download. According to the median value of relative expression of NMU mRNA (2.740), the patients were divided into the high expression group (>2.740) and the low expression group (<2.740), with 89 cases in each group. GSEA software was used to analyze the biological functions and pathways in which the genes enriched significantly. The molecules and key targets for molecular docking were explored using the large molecule protein interaction tool PDBePISA. Spearman correlation analysis was performed using R language data packets. Results:The results of C57BL/6 NMU -/- mouse genotypes analyzed by using the gel electrophoresis pattern of PCR amplification products of tail tissues showed that the wild type was one 380 bp electrophoretic band, the homozygous type was one 450 bp electrophoretic band, and the heterozygous type was 450 bp and 380 bp electrophoretic bands. After identifying and screening pure strains mouse, reproduction was carried out, and C57BL/6 NMU -/- homozygous mice were successfully obtained. The results of flow cytometry analysis showed that the proportion of CD8 + T cells in the spleen tissues of C57BL/6 NMU -/- wild-type and homozygous pancreatic tumor bearing mice was (30.38±0.37)% and (37.00±0.48)%, with a statistically significant difference between the two groups ( t = 9.79, P < 0.001). The absolute values of CD8 + T cells were (8.36±0.27)×10 4 and (10.20±0.28)×10 4, respectively, and the difference was statistically significant ( t = 3.71, P = 0.013). In the GEO database GSE102238 and GSE62452 datasets, there were differentially expressed genes in pancreatic cancer tissues compared with adjacent tissues, including 219 up-regulated genes and 325 down-regulated genes in pancreatic cancer tissues; among them, NMU was an upregulated differentially expressed gene. The relative expression of NMU mRNA in patients aged > 65 year or grade G3-G4 was higher than that in patients aged ≤ 65 years or grade G1-G2, and the differences were statistically significant (both P < 0.05). The analysis results of CIBERSORT algorithm showed that the expression abundance of CD8 + T cells, initial CD4 + T cells, activated memory CD4 + T cells, and γδ T cells in the high expression group of NMU was lower than that in the low expression group (all P < 0.05). The overall survival of the high expression group of NMU was worse than that of the low expression group in the OncoLnc database ( P = 0.010). GSEA enrichment analysis and Spearman correlation analysis revealed significant changes in the Hedgehog signaling pathway, biosynthesis of unsaturated fatty acids and pyrimidine nucleotide metabolism, which affected tumor metabolic remodeling. Conclusions:NMU may remodel the tumor microenvironment of pancreatic cancer by regulating Hedgehog signaling pathway.
10.Role of Toll-like receptor 4 in regulation of homocysteine-induced ferroptosis in macrophages
Jun-jie ZHAI ; Shaoying WEN ; Xinru LI ; Rui SUN ; Ning QI ; Qifan ZHANG ; Li YANG ; Hui HUANG ; Lingju MA ; Yinju HAO ; Yideng JIANG ; Guizhong LI ; Shengchao MA
The Journal of Practical Medicine 2025;41(3):313-321
Objective To investigate the role of Toll-like receptor 4(TLR4)in the regulation of homocys-teine(Hcy)-induced ferroptosis in macrophages.Methods Mouse macrophage cells RAW264.7 were cultured and divided into control group,Hcy intervention group(Hcy group),and Hcy plus ferroptosis inhibitor group(Hcy+Fer-1 group).After transfection with interference fragments,macrophages were treated with Hcy,and then divided into control group,Hcy intervention group(Hcy group),TLR4 interference negative control plus Hcy intervention group(si-NC+Hcy group),and TLR4 interference plus Hcy intervention group(si-TLR4+Hcy group).Macrophages were transfected with overexpression lentivirus and treated with Hcy,then were divided into control group,Hcy intervention group(Hcy group),a TLR4 overexpression negative control plus Hcy intervention group(OE-NC+Hcy group),and a TLR4 overexpression plus Hcy intervention group(OE-TLR4+Hcy group).After 48 hours of intervention,real-time fluorescent quantitative PCR and western blot were used to detect the expression levels of TLR4 in macrophages treated with Hcy;western blot was used to detect the expression levels of ferroptosis-related proteins ACSL4,GPX4,and FTH1 in macrophages,and ferrous ion assay kit to detect the concentration of Fe2+in macrophages;reactive oxygen species(ROS)assay kit and laser confocal microscopy were used to detect the content of intracellular reactive oxygen species.Results Compared with those in the control group,the expression level of the pro-ferroptosis protein ACSL4 was increased in the Hcy group(P<0.05),while the expression levels of anti-ferroptosis proteins GPX4 and FTH1 were decreased(P<0.05);the concentration of Fe2+was increased(P<0.05),and the content of ROS was increased.Meanwhile,the protein and mRNA expres-sion levels of TLR4 were both increased in the Hcy group(P<0.05).After macrophages were transfected with TLR4 interference fragments,compared with those in the si-NC+Hcy group,the expression levels of GPX4 and FTH1 were increased(P<0.05);the expression level of ACSL4 was decreased(P<0.05);the concentration of Fe2+was decreased(P<0.05),and the content of ROS was reduced in the si-TLR4+Hcy group.After macro-phages were transfected with TLR4 overexpression lentivirus,compared with those in the OE-NC+Hcy group,the expression levels of GPX4 and FTH1 were decreased(P<0.05),and the expression level of ACSL4 was increased(P<0.05)in the OE-TLR4+Hcy group.Conclusion Hcy induces the occurrence of ferroptosis in macrophages,and Toll-like receptor 4 has a positive feedback regulatory effect on ferroptosis in macrophages.

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