1.Mechanism of Danggui Shaoyaosan in Improving Glomerulosclerosis in db/db Mice via SIRT1/HIF-1α/VLDLr Signaling Pathway
Ruijia LI ; Zixuan WANG ; Shilong GUO ; Jing LI ; Qianqian ZHANG ; Wen DONG ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):11-18
ObjectiveTo investigate the potential mechanism of Danggui Shaoyaosan (DSS) in ameliorating renal injury in db/db mice. MethodsThirty 8-week-old specific pathogen-free (SPF)-grade male db/db mice and six db/m mice were acclimated for one week. Urinary microalbumin and blood glucose levels were measured weekly in both db/db and db/m mice. Successful modeling was determined by significantly higher microalbuminuria in db/db mice compared to db/m mice and a fasting blood glucose ≥16.7 mmol·L-1. The 30 db/db mice were randomly divided into five groups: the model group, the irbesartan (IBN) group, and three DSS dose groups (low-, medium-, and high-dose DSS groups, administered at 16.77, 33.54, 67.08 g·kg-1·d-1, respectively). Additionally, the six db/m mice served as the normal control group. The IBN group received irbesartan at 0.025 g·kg-1·d-1 by gavage, while the three DSS groups received DSS at 16.77, 33.54, and 67.08 g·kg-1·d-1 by gavage, respectively. The normal and model groups were administered with an equivalent volume of normal saline by gavage. All interventions lasted for 8 consecutive weeks. After intervention, serum creatinine (SCr), blood urea nitrogen (BUN), urinary total protein (UTP), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were measured to evaluate the therapeutic efficacy of the treatments. Renal histopathological changes were observed with hematoxylin-eosin (HE) staining. Western blot was used to detect the protein expression of silencing information regulator 1 (SIRT1), hypoxia-inducible factor-1α (HIF-1α), very low-density lipoprotein receptor (VLDLr), and cluster of differentiation 31 (CD31). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA levels of HIF-1α and VLDLr. Immunohistochemistry was used to observe the expression and distribution of HIF-1α and Caspase-3. ResultsCompared to the normal group, the model group showed significantly increased SCr, BUN, UTP, TG, and LDL-C. HE staining revealed glomerulosclerosis, mesangial matrix hyperplasia, capillary loop distortion and thickening, with extensive inflammatory cell infiltration. Protein expression of SIRT1 and CD31 significantly decreased (P<0.05), while HIF-1α and VLDLr protein and mRNA levels increased (P<0.05). Immunohistochemistry showed increased expression of HIF-1α and Caspase-3 (P<0.05), indicating hypoxia and apoptosis in renal cells. In all treatment groups, SCr, BUN, TG, and LDL-C were significantly reduced compared to the model group (P<0.05), and UTP was significantly improved in the medium-dose DSS group (P<0.05). Renal tissue structure and morphology were improved, inflammatory cells were reduced, and no vascular hyaline degeneration was observed. SIRT1 and CD31 protein expression was elevated to varying degrees compared to the model group (P<0.05), while HIF-1α and VLDLr protein and mRNA levels decreased (P<0.05). Immunohistochemistry showed reduced expression of HIF-1α and Caspase-3 in all treatment groups (P<0.05), with the most significant improvement observed in the IBN group and medium-dose DSS group (P<0.05). ConclusionDSS can effectively ameliorate glomerulosclerosis and lipid deposition in db/db mice, and its mechanism may involve the SIRT1/HIF-1α/VLDLr signaling pathway.
2.Protective Effect and Potential Mechanism of Danggui Shaoyaosan on Diabetic Kidney Disease in db/db Mice Based on Endoplasmic Reticulum Stress in Glomerular Endothelial Cells
Ruijia LI ; Zixuan WANG ; Shilong GUO ; Sen YANG ; Jing LI ; Qianqian ZHANG ; Wen DONG ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):28-35
ObjectiveTo investigate the therapeutic efficacy of Danggui Shaoyaosan (DSS) on renal injury in db/db mice and its impact on endoplasmic reticulum stress (ERS) in renal tissues. MethodsThirty 8-week-old male db/db mice and six db/m mice were acclimated for one week, after which urinary microalbumin and blood glucose levels were monitored to establish a diabetic kidney disease (DKD) model. The model mice were randomly divided into a model group, an irbesartan group, and three DSS treatment groups with different doses (16.77, 33.54, and 67.08 g·kg-1·d-1). A normal group was set as control. Each group was intragastrically administered with the corresponding drugs or saline for 8 weeks. After the intervention, general conditions were observed. Serum cystatin C (Cys-C), 24-hour urinary total protein (24 h-UTP), 24-hour urinary microalbumin (24 h-UMA), urinary creatinine (Ucr), and urea nitrogen (UUN) were measured. Transmission electron microscopy (TEM) was used to observe glomerular basement membrane (GBM) and ultrastructural changes of the endoplasmic reticulum (ER) in glomerular endothelial cells. Western blot, real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and immunohistochemistry were used to analyze renal tissue structure and the expression of GRP78, CHOP, and related markers. ResultsCompared with the normal group, the mice in the model group showed curled posture, sluggish response, poor fur condition, increased levels of Cys-C, 24 h-UTP, 24 h-UMA, and UUN (P<0.05), while Ucr decreased (P<0.05). The GBM was significantly thickened, with podocyte and foot process fusion. The protein expressions of GRP78, CHOP, and ATF6 were significantly upregulated (P<0.05), the mRNA levels of GRP78 and CHOP increased (P<0.05), and immunohistochemistry showed an enhanced GRP78 signal (P<0.05). After treatment, the mice exhibited improved behavior, normalized GBM and podocyte structure, improved ER morphology and markedly better biochemical indicators. Western blot, Real-time PCR, and immunohistochemistry indicated that the ERS-related markers were downregulated in the DSS treatment groups (P<0.05), suggesting alleviated ERS and improved renal function. ConclusionDSS can effectively ameliorate renal pathological damage in db/db mice, possibly by regulating ERS in glomerular endothelial cells, although the underlying signaling mechanisms require further investigation.
3.A preliminary investigation on the carriage of Bartonella by rodents at key ports in western Inner Mongolia
Ruo-wen GUO ; Huai-bo WEI ; Peng LUO ; Xia LIU ; Zong-di LIU ; Jing WU ; Jia XU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):134-140
Objective This study investigated the diversity of rodent populations and the infection status of Bartonella at three ports along the China-Mongolia border in 2022. Methods Rodents at three Belt and Road ports along the China-Mongolia border, namely Ganqimaodu, Erenhot, and Zhuengadabuqi, were morphologically identified. The Bartonella citrate synthase(gltA)gene was amplified by nested polymerase chain reaction(PCR), and PCR-positive products were sequenced. The resulting sequences were then analyzed for genetic characteristics. Phylogenetic analysis was performed using MEGA 11.0 software using Neighbor-Joining and Maximum-Likelihood method. Results A total of 94 rodents were captured, representing seven species from five families and six genera: Mus musculus, Meriones unguiculatus, Meriones meridianus, Spermophilus dauricus, Allactaga sibirica, Dipus sagitta, and Phodopus roborovskii. Among them, M. unguiculatus was the most abundant species, with 58 rodents, accounting for 61.70% of the total. Overall,11 positive Bartonella pathogen sequences were obtained from the three ports, with a positive detection rate of 11.70%(11/94). The infected rodent species included M. unguiculatus, M. meridianus, and A. sibirica, and two species of Bartonella were detected. Conclusions Rodents at Ganqimaodu, Erenhot, and Zhuengadabuqi ports along the China-Mongolia border were naturally infected with Bartonella. Rodent monitoring and pathogen prevention and control in this area should be strengthened.
4.Liraglutide may alleviate acetaminophen-induced liver injury by enhancing autophagy
Guo-jing XING ; Wen-bin LI ; Long-long LUO ; Li-fei WANG ; Yuan DENG ; Zhen WANG ; Zhao-jie ZHANG ; Xiao-hui YU ; Jiu-cong ZHANG
Chinese Pharmacological Bulletin 2025;41(10):1867-1875
Aim To investigate the protective effect of liraglutide(LIRA)on acetaminophen(APAP)-in-duced hepatotoxicity at the in vivo level and to reveal the underlying mechanism.Methods Forty SPF grade male C57BL/6J mice were randomly divided into the Control,LIRA(200 μg·kg-1),APAP(500 mg·kg-1),LIRA+APAP,LIRA+APAP+3-methylade-nine(3-MA,30 mg·kg-1)groups,with eight mice in each group.The mice were administered for three con-secutive days,and the materials were taken after 24 h.The general condition and body weight of mice in each group were recorded,and liver morphology was ob-served.Serum ALT and AST levels,as well as SOD ac-tivity,MDA,and GSH content in liver homogenates,were measured using biochemical assay kits.The levels of inflammatory cytokines IL-6,TNF-α,and IL-1β in serum were detected by ELISA.Liver pathological changes were assessed by HE staining,while mitochon-drial and autophagosome structures in liver tissues were observed using transmission electron microscopy.The number of PCNA-positive cells in liver tissues was e-valuated using immunohistochemical staining.The pro-tein expression levels of LC3Ⅱ,p62,Bax,Bcl-2,PC-NA,and CyclinD1 in liver tissues were determined by Western blot.Results LIRA pretreatment can im-prove the general condition of mice with acetamino-phen-induced liver injury(AILI),reduce serum ALT and AST levels,and effectively ameliorate the appear-ance and morphology of the liver as well as the patho-logical damage to liver tissue.Simultaneously,the lev-els of inflammatory cytokines IL-6,TNF-α,and IL-1βare significantly decreased;SOD activity and GSH con-tent are significantly increased,while MDA content is significantly reduced.Transmission electron microsco-py observations reveal the presence of numerous auto-phagosomes in the cytoplasm of liver tissue.Immuno-histochemical staining results indicate a significant in-crease in the number of PCNA-positive cells.Further-more,the expression of LC3Ⅱ,Bcl-2,PCNA,and Cy-clinD1 proteins in liver tissue is significantly upregulat-ed,while the expression of p62 and Bax proteins is significantly downregulated.However,after interven-tion with the autophagy inhibitor 3-MA,the aforemen-tioned protective effects of LIRA are significantly.Conclusions LIRA pretreatment can significantly im-prove liver injury in AILI mice.Its protective mecha-nism may be related to enhancing autophagy in hepato-cytes,thereby reducing oxidative stress,inflammatory response and apoptosis in liver of AILI mice.
5.Effect of dual-site repetitive transcranial magnetic stimulation on the changes of brain function in patients with subjective tinnitus
Guo-qing JING ; Feng WEN ; Lu YU ; Qi HAN ; Wen-jing WU ; Yang ZHANG
Journal of Regional Anatomy and Operative Surgery 2025;34(4):305-309
Objective To detect the characteristics of whole-brain functional changes in patients with subjective tinnitus(ST)after"frontal-temporal"dual-site repetitive transcranial magnetic stimulation(rTMS)by resting-state functional magnetic resonance imaging(rs-fMRI).Methods A total of 45 ST patients were enrolled,and assessments of tinnitus severity and rs-fMRI scans were performed before and 2 weeks after treatment with"frontal-temporal"dual-site rTMS.Regional homogeneity(ReHo),fractional amplitude of low-frequency fluctuations(fALFF),degree centrality(DC)and seed-based functional connectivity(FC)were analyzed before and after treatment in ST patients.Results Tinnitus handicap inventory(THI)score of ST patients 2 weeks after treatment was significantly decreased compared with that before treatment(P<0.001).ReHo values of the right inferior parietal lobule decreased,fALFF values of the right temporal pole increased,fALFF values of the right superior temporal gyrus decreased,and DC(weighted)and DC(Binarized)values of the right medial temporal gyrus all decreased in ST patients 2 weeks after treatment compared with those before treatment(P<0.05,GRF correction).Using the above differential brain regions as seed points for FC analysis,FC values between right superior temporal gyrus(fALFF)and right middle temporal gyrus reduced,FC values between right middle temporal gyrus[(DC(weighted)]and right superior occipital gyrus reduced,and FC values between right middle temporal gyrus[DC(Binarized)]and right superior occipital gyrus reduced 2 weeks after treatment compared with those before treatment(P<0.05,GRF correction).Conclusion"Frontal-temporal"dual-site rTMS is initially effective for ST patients,and the auditory and non-auditory brain regions of ST patients showed different degrees of regional and interbrain function changes,mainly involving default mode network and visual-auditory network.
6.Identification of chemical components of Angelica sinensis using UPLC-Q-TOF/MS and its the effect and mechanism of activating blood circulation
Wen-xing JIAO ; Jiang-xia WEI ; Jing-jing GUO ; Zhi-jun YANG ; Xi-cang YANG ; Xiu-juan YANG
Chinese Pharmacological Bulletin 2025;41(1):147-156
Aim To identify the chemical components of Angelica sinensis(AS)and explore the mechanism of AS in activating blood circulation.Methods UP-LC-Q-TOF-MS was used to identify the chemical com-ponents of AS.The changes of syndrome and patholog-ical section of heart in rats were observed.Hemody-namics and proteomics were measured.Results A to-tal of 270 compounds were identified from AS.It showed that rats of Angelica sinensis group were greatly improved such as arched back,shrugged fur,huddled up and less mobile,purplish paws and tails,whitish ear margins and nasolabial lips,reduced drinking and feed-ing,and slow response to external stimuli;mildly disor-dered myocardial fibre arrangement,myofibre arrange-ment was tighter than that of model group,myocardial fibres were narrower and close to normal,and mild oe-dema,exudation,and inflammatory cell infiltration could be seen in the surrounding area;SAP was signif-icantly lower and LVSP was significantly higher in An-gelica sinensis group(P<0.05).Proteomics showed that 62 differential proteins were screened in Angelica sinensis group compared to model,GO function were concentrated in the extracellular matrix,cytoskeletal proteins binding and protein hydrolysis negatively regu-lated.KEGG pathway were enriched in signalling path-ways such as complement and coagulation cascades,cellular focal adhesion,leukocyte transendothelial mi-gration and chemokine signalling pathways.Conclu-sions AS probably through the expression of proteins,which modulate the signalling pathways of the comple-ment and coagulation cascade reactions and the con-traction of vascular smooth muscle.
7.Effects of rotating magnetic fields on sevoflurane-induced cognitive impairment in elderly rats
Can WANG ; Zhipeng WEN ; Yanwen HU ; Jing CAI ; Yunliang GUO
Chinese Journal of Medical Physics 2025;42(8):1102-1108
Objective To investigate the ameliorative effect and the related mechanism of rotating magnetic fields(RMF)on sevoflurane(SEV,a commonly used inhalational anesthetics in clinics)-induced cognitive impairments in elderly rats.Methods The cognitive functions of 24 elderly male SD rats which were allocated into 3 experimental groups(Control group,SEV group,and SEV+RMF group;n=8 per group)were assessedviawater maze testing,and the damage and repair of hippocampal neurons were detected using ELISA and Western blotting assays.Water maze testing was also conducted on additional 24 elderly male SD rats which were randomized into 3 groups(SEV group,SEV+RMF group,and SEV+autophagy inhibitor+RMF group;n=8 per group)for assessing their cognitive functions.Results Compared with SEV group,RMF intervention significantly reduced the escape latency and swimming distance in water maze test(P<0.01),while increasing the number of platform crossovers(P<0.001).RMF downregulated the serum levels of tumor necrosis factor-α,interleukin-1β,and interleukin-6 in SEV-treated rats(P<0.001),and led to remarkable reductions in both serum neuron-specific enolase and β-amyloid protein levels(P<0.001).Moreover,RMF upregulated the expressions of nerve growth factor and brain-derived neurotrophic factor in hippocampal neurons(P<0.001),suppressed the expression of apoptotic protein caspase-3 and autophagy related protein p62 in the hippocampus,and upregulate the expression of autophagy related protein Beclin-1(P<0.001).However,the administration of autophagy inhibitor 3-MA abolished the ameliorative effects of RMF on SEV-induced cognitive impairments in elderly rats(P<0.001).Conclusion RMF can effectively improves SEV-induced cognitive dysfunction in elderly rats,and this neuroprotective effect is mediated by the autophagy activation in hippocampal neurons.
8.Effects of rotating magnetic fields on sevoflurane-induced cognitive impairment in elderly rats
Can WANG ; Zhipeng WEN ; Yanwen HU ; Jing CAI ; Yunliang GUO
Chinese Journal of Medical Physics 2025;42(8):1102-1108
Objective To investigate the ameliorative effect and the related mechanism of rotating magnetic fields(RMF)on sevoflurane(SEV,a commonly used inhalational anesthetics in clinics)-induced cognitive impairments in elderly rats.Methods The cognitive functions of 24 elderly male SD rats which were allocated into 3 experimental groups(Control group,SEV group,and SEV+RMF group;n=8 per group)were assessedviawater maze testing,and the damage and repair of hippocampal neurons were detected using ELISA and Western blotting assays.Water maze testing was also conducted on additional 24 elderly male SD rats which were randomized into 3 groups(SEV group,SEV+RMF group,and SEV+autophagy inhibitor+RMF group;n=8 per group)for assessing their cognitive functions.Results Compared with SEV group,RMF intervention significantly reduced the escape latency and swimming distance in water maze test(P<0.01),while increasing the number of platform crossovers(P<0.001).RMF downregulated the serum levels of tumor necrosis factor-α,interleukin-1β,and interleukin-6 in SEV-treated rats(P<0.001),and led to remarkable reductions in both serum neuron-specific enolase and β-amyloid protein levels(P<0.001).Moreover,RMF upregulated the expressions of nerve growth factor and brain-derived neurotrophic factor in hippocampal neurons(P<0.001),suppressed the expression of apoptotic protein caspase-3 and autophagy related protein p62 in the hippocampus,and upregulate the expression of autophagy related protein Beclin-1(P<0.001).However,the administration of autophagy inhibitor 3-MA abolished the ameliorative effects of RMF on SEV-induced cognitive impairments in elderly rats(P<0.001).Conclusion RMF can effectively improves SEV-induced cognitive dysfunction in elderly rats,and this neuroprotective effect is mediated by the autophagy activation in hippocampal neurons.
9.Role of GLUT1-dependent glycolysis in attenuation of oxygen-glucose deprivation-reoxygenation injury by dexmedetomidine in HK-2 cells
Wei DING ; Wen-hui TAO ; Yu-le WU ; Jian-xiao WU ; Jing-yi GUO ; Li-fang XIE ; Bing-qian FAN ; Xue-song GU ; Yang LI ; Xian-wen HU
Chinese Pharmacological Bulletin 2025;41(3):444-450
Aim To evaluate the role of the glucose transporter protein 1(GLUT1)-dependent glycolytic in the attenuation of oxygen-glucose deprivation-reoxygen-ation(OGD/R)injury in HK-2 cells by dexmedetomi-dine(Dex).Methods C57/BL6 mice were random-ly divided into three groups(n=6),namely,sham operation group(Sham group),renal ischemia reper-fusion group(I/R group)and Dex group(I/R+Dex group).Serum creatinine(Cr)and urea nitrogen(BUN)were measured,while the levels of key glyco-lytic enzymes HK2,PFKFB3 and GLUT1 were meas-ured.HK-2 cells were cultured and randomised into seven groups(n=6),which was treated with OGD/R,overexpression or interference with GLUT1,Dex and glycolysis inhibitor 2-DG.CCK-8 and LDH activi-ty were used to detect cellular damage.Glycolysis lev-els were detected by lactate and ECAR.The inflamma-tory level was reflected by qRT-PCR for IL-6 and TNF-α.qRT-PCR and Western blot were performed to de-tect the levels of GLUT1,HK2,and PFKFB3.Results Dex significantly ameliorated kidney injury and HK-2 cell injury(P<0.05).Dex inhibited the OGD/R-induced rise in lactate and extracellular acidification rate(ECAR),as evidenced by suppression of the ex-pression of GLUT1,HK2 and PFKFB3(P<0.05).In vitro experiments showed that GLUT1 knockdown sig-nificantly improved OGD/R-induced cellular damage.Lactate,ECAR,glycolysis-related mRNAs and pro-teins were inhibited by GLUT1 knockdown(P<0.05).Significantly,there were no significant differ-ences in above indexes after Dex treatment based on GLUT1 knockdown.Overexpression of GLUT1 abroga-ted the protective effects of Dex,while reversing the inhibitory effects of Dex on the expression of GLUT1,HK2,and PFKFB3(P<0.05).Conclusions Dexmedetomidine attenuates OGD/R induced injury in HK-2 cells by inhibiting GLUT1-dependent glycolysis.
10.Latent profile analysis of health risk behaviors among students aged 11 to 18 years in Minhang District,Shanghai
Qin-wen YANG ; Hui-jing SHI ; Yan HAN ; Qi GUO
Fudan University Journal of Medical Sciences 2025;52(1):31-37
Objective To explore the potential categories of health risk behaviors among students aged 11 to 18 years in Minhang District,Shanghai in order to identify the influencing factors of health risk behaviors among different categories of students.Methods Using stratified cluster sampling techniques,a random selection of 1 690 middle school students from Minhang District,Shanghai,were chosen as the study sample.Data was collected using the"Shanghai Adolescent Health-Related Behavior Survey Questionnaire"to assess participants'scores on six categories of health risk behaviors.Latent profile analysis(LPA)was employed to cluster students'health risk behaviors,and a multifactorial Logistic regression model was used to analyze the related influencing factors.Results The health risk behaviors of students aged 11 to 18 in Minhang District,Shanghai,were categorized into 3 groups:Class 1,comprising 915 students(54.14%),with moderate to low scores in health risk behaviors,named"the group with moderately low levels of various health risk behaviors";Class 2,comprising 539 students(31.89%),with higher scores in psychological addiction,named"the group with psychological addiction as the prominent health risk behavior";Class 3,comprising 236 students(13.97%),with higher scores in substance addiction,named"the group with substance addiction as the prominent health risk behavior".The results of the univariate analysis for the three potential categories of student health risk behaviors show that there are statistically significant differences in the 3 potential categories of health risk behaviors among students of different schools,ages,ethnicities,and boarding situations(P<0.05).The analysis results of the multivariate Logistic regression indicate that compared to junior high school students,both senior high school students and vocational high school students have a higher risk of exhibiting unhealthy behaviors characterized by psychological addiction and substance addiction,with all differences being statistically significant(P<0.05).Conclusion The latent profile analysis reveals three distinct categories of health risk behaviors among students aged 11 to 18 years in Minhang District,Shanghai,with significant distribution differences among students from diverse backgrounds.Consequently,it is recommended that tailored health education and intervention measures be implemented for students with different school characteristics and at various educational stages.


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