ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

Objective To obtain measurements of fetal four-chamber view and left and right ventricular shapes using two-dimensional speckle tracking,and to explore the clinical quantification of cardiac shape remodeling in small for gestational age(SGA)fetuses.Methods In this study,we prospectively collected data on singleton pregnancies from 28 to 39 weeks that were established in the archives of Obstetrics and Gynecology Hospital,Fudan University from May 2020 to Jul 2021.Fetuses eligible for inclusion criteria were randomly matched according to the ratio of estimated fetal weight(EFW)≥10th percentile(P10)∶EFWP90 in the apical segments of the left ventricle was greater in normal UAPI fetuses than that in low-risk fetuses(24.2%vs.14.3%,P=0.005);the SI of left ventricle in UAPI-normal SGA fetuses was greater in segments S1 to S22 than that of right ventricle with statistically significant difference(all P<0.05),while no significant difference was found between the SI of left and right ventricles in segments S23 and S24.Conclusion About one-fourth of SGA fetuses with normal UAPI have abnormally increased apical segments of the left ventricular SI,suggesting that cardiac remodeling with a predominantly"elongated"apical segments of the left ventricle precedes Doppler anomalies.

Objective To compare the difference,agreement,and axial length measurement success rate between biometers ZW-30 and IOLMaser 700 based on swept-source optical coherence tomography for the measurement of ocular bi-ological parameters in patients with cataracts.Methods A total of 126 cataract patients(233 eyes)who were advised to undergo cataract surgery at the Department of Ophthalmology at Beijing Tongren Hospital,Capital Medical University from January to February 2024 were included in this study.Two biometers were used to measure the axial length(AL),mean keratometry(Km),anterior chamber depth(ACD),lens thickness(LT),central corneal thickness(CCT),and horizontal corneal diameter[namely,the white-to-white(WTW)distance].The axial measurement success rate of the two biometers and the difference and agreement between the parameters were calculated.Results The mean difference between ZW-30 and IOLMaster 700 was(-0.006±0.042)mm for AL,(-0.074±0.204)D for Km,(0.031±0.051)mm for ACD,(0.001±0.005)mm for CCT,and(-0.286±0.337)mm for WTW,and the differences were statistically significant(all P＜0.05).The mean difference between ZW-30 and IOLMaster 700 was(0.008±0.215)mm for LT,and the difference was not statis-tically significant(t=0.579,P=0.563).The 95％limits of agreement range was between-0.011 mm and 0.000 mm for AL,between-0.474 D and 0.326 D for Km,between-0.010 mm and 0.012 mm for CCT,between-0.068 mm and 0.131 mm for ACD,between-0.116 mm and 0.159 mm for LT,and between-0.947 mm and 0.376 mm for WTW.The intra-class correlation coefficient of all measurements ranged from 0.790 to 1.000.The AL measurement success rate of IOLMaster 700 and ZW-30 was 95.3％and 95.7％,respectively.The latter had an AL measurement success rate of 98.7％after manually marking the position of the retinal identification line.Conclusion There were statistically significant differences between ZW-30 and IOLMaster 700 in the measurement of the AL,Km,ACD,and CCT,which,however,were not clinically significant.The agreement between both was good.ZW-30 had a higher AL measurement success rate,espe-cially for the manual identification function of eyes with opacified refractive media,which can further improve the AL meas-urement success rate and provide reference for clinical work.

Aim To investigate the role of triggering receptor expressed on myeloidcells 2(TREM2)in syn-aptic plasticity induced by cocaine addiction.Methods C57BL/6J mice and Trem2 knockout mice were uti-lized in this study to evaluate the alterations in postsyn-aptic density protein 95(PSD-95)and synapsin 1(SYN1)within the cortex and hippocampus of co-caine-addicted mice by using immunological tech-niques.Results HE staining and Nissl staining showed increased neuronal damage in the hippocampus and cortex of mice after cocaine addiction.The results of immunohistochemistry and fluorescence of PSD-95 and SYN1 were consistent with the expression trend of Western blot.In the wild type mouse model,the ex-pression level of PSD-95 in the hippocampus and cortex was lower than that in the saline group,and the ex-pression of SYN1 was higher than that in the saline group.In the knockout mouse model,the expression levels of PSD-95 and SYN1 in the hippocampus and cortex were significantly higher than those in the saline group after cocaine addiction.The expression levels of PSD-95 and SYN1 in the hippocampus and cortex of cocaine knockout mice were higher than those of co-caine wild type mice.Conclusion Cocaine addiction can change the synaptic plasticity,and TREM2 plays a regulatory role in the synaptic plasticity of hippocampus and cortex in mice with cocaine injury.TREM2 is ex-pected to be a new target for studying the mechanism of cocaine addiction.

Cyclic GMP-AMP synthase(cGAS)is a congenital immune sensor that can recognize cytoplasm abnormal dsDNA.By catalyzing the second messenger cyclic GMP-AMP(cGAMP)formation,it activates stimulator of interferon genes(STING),releases type Ⅰ interferon and inflammatory cytokines,activates the host immune response,and participates in cerebral ischemia reperfusion injury(CIRI)cascade reaction.This article reviews the research progress of the mechanism of cGAS-STING signaling pathway participation in CIRI,hoping to provide ideas for its treatment.

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.

Objective:To observe the efficacy of probiotics in the adjuvant treatment of bronchial asthma and to explore the relationship between their action and intestinal flora.Methods:A total of 76 newly diagnosed patients with mild-to-moderate bronchial asthma treated at Baotou Central Hospital between November 2023 and January 2025 were randomly divided into two groups:the conventional treatment group(n=38)and the combined probiotic treatment group(n=38).Post-treatment comparisons were made between the two groups regarding symptom resolution time,Asthma Control Test(ACT)scores,lung function,fractional exhaled nitric oxide(FeNO)levels,serum inflammatory cytokines,complement levels,and other indicators.Faecal samples were collected for 16S rDNA sequencing of gut microbiota.Results:Baseline characteristics showed no significant differences between the two groups(P＞0.05).Compared to the conventional treatment group,the combined probiotic group exhibited significantly shorter resolution times for asthma symptoms and lung rales(P＜0.001),significantly higher ACT scores,FEV1,and PEF(P＜0.001),and significantly lower FeNO levels(P＜0.001).Additionally,serum interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and complement C3 levels were significantly reduced(P＜0.001),while serum interleukin-6(IL-10)levels were significantly increased(P＜0.001).16S rDNA sequencing revealed no significant changes in gut microbiota richness or diversity in the conventional treatment group before and after treatment(P＞0.05),whereas intestinal flora richness and diversity were significantly increased in the combined probiotic treatment group compared to the pre-treatment group(P＜0.05).Correlation analysis between gut microbiota and inflammatory markers demonstrated that Faecalibacterium and Bifidobacterium abundance were negatively correlated with TNF-α levels(P＜0.05),while Escherichia-Shigella,and Streptococcus abundance were positively correlated with TNF-α levels(P＜0.05).Streptococcus and Klebsiella abundance were positively correlated with IL-6 levels(P＜0.05).Escherichia-Shigella and Streptococcus abundance were negatively correlated with IL-10 levels and positively correlated with complement C3 levels(P＜0.05).Conclusion:Probiotics may assist in improving bronchial asthma symptoms by influencing the gut flora to reduce the inflammatory response.

Post-stroke depression(PSD),a common stroke complication characterized by depressed mood and diminished interest,severely affects patients'recovery and quality of life.Microglial abnormal activation and polarization play key roles in PSD pathogenesis,closely associated with neuroinflammation and imbalance in neu-rotransmitter metabolism.In contrast,traditional Chinese medicine(TCM)demonstrates unique multi-target and multi-level mechanisms:regulating microglial function,ameliorating post-stroke neuroinflammatory environments,and promoting neuroplasticity,thereby potentially alleviating PSD symptoms.This review summarizes TCM's effects on microglial activation/polarization states and its therapeutic advances in PSD,providing novel perspectives and strategies for clinical management.

Aim To explore the mechanism of luteolin in alleviating hepatic fibrosis.Methods C57BL/6 mice were randomly divided into the control group,CCl4 group,silybin group(100 mg·kg-1)and luteo-lin group(100 mg·kg-1).After 10-week modeling and 2-week treatment,the serum levels of aminotrans-ferase and liver histopathology were examined.Hepatic fibrosis and autophagy-related gene expression were as-sessed using immunohistochemistry and immunofluores-cence.Human hepatic stellate cell line(LX2)was cultured and divided into control,TGF-β1(10 mg·L-1),TGF-β1+silybin(40 μmol·L-1),TGF-β1+luteolin(40 μmol·L-1).Fibrotic and autophagy-re-lated markers were analyzed using quantitative real-time PCR,Western blot,immunofluorescence and MDC staining.Results Compared with the CCl4 group,the treatment groups showed significantly improved liver function and reduced hepatic fibrosis,with markedly downregulated COL1A1 and α-SMA expression,and luteolin demonstrated superior efficacy.Compared with TGF-β1 group,luteolin treatment significantly de-creased mRNA levels of COL1A1,ACTA2 and MAP1LC3B,while increasing the mRNA level of SQSTM1,the protein levels of COL1A1 and α-SMA de-creased,p62 was enhanced,the LC3Ⅱ/Ⅰ ratio was downregulated,and autophagy was reduced.These effects of luteolin were reversed by autophagy inducer rapamycin.Conclusion Luteolin alleviates liver fi-brosis by decreasing the autophagy of hepatic stellate cells.

Aim To investigate the effect of Huangqi injection(HI)and Huangqi oral solution(HO)on cisplatin-induced nephrotoxicity(CIN)based on un-targeted metabolomics technology and the underlying mechanisms.Methods Sprague Dawley(SD)rats were randomly divided into the blank group,cisplatin(CDDP)model group,HI treatment group,and HO treatment group,then the CIN model was built with low dose multiple intraperitoneal injections of CDDP.Pre-liminary evaluation of the renal protective efficacy of HI and HO was performed by measuring serum creatinine(Scr),blood urea nitrogen(BUN),and organ indi-ces.Further screening and identification of potential biomarkers(PBs)related to CIN and HI/HO pharma-cological effects were attained through metabolomics studies of renal tissues,and pathway enrichment analy-sis was conducted.Results HI and HO significantly restored the abnormal increase in renal function indica-tors and abnormal decrease in organ indices caused by CDDP,as well as significantly improved the abnormal renal metabolic profile induced by CDDP,indicating that both HI and HO had good alleviating effects on CIN.HI significantly reversed 47 out of 54 CIN related PBs,mainly involving metabolic pathways such as glycerophospholipid metabolism,tryptophan metabo-lism,pantothenate and CoA biosynthesis;HO signifi-cantly reversed 18 out of 54 CIN related PBs,mainly involving metabolic pathways such as taurine and hypo-taurine metabolism,ascorbate and aldarate metabo-lism,pentose and glucuronate interconversions.Con-clusions Both HI and HO have significant alleviating effects on CIN.In the short term,HI salleviating effect is superior to that of HO.Overall,the mechanisms by which both alleviate CIN are mainly related to regula-ting lipid metabolism,amino acid metabolism.