Aim To reveal the mechanism of CIP4 homologs protein 1(RICH1)are involved in the regu-lation of myocardial fibrosis.Methods Mouse cardiac fibroblasts(MCFs)cells were treated with transforming growth factor-β(TGF-β1)to induce the formation of a myocardial fibrosis cell model;the level of the target protein was detected by Western blotting;and the RICH1 gene was detected by transfection of the cells with plasmid.The RICH1 gene was overexpressed(RICH 1 OE)using plasmid transfection;the RICH1 gene was silenced using siRNA fragment(siRICH1);and the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3 a1,and Acta2,were de-tected using RT-qPCR.Results RICH1 was signifi-cantly down-regulated in TGF-β1-treated MCFs;the expression levels of myocardial fibrosis marker genes,such as Col1 a1,Col3a1,and Acta2,were down-regu-lated in the RICH1 OE+TGF-β1 group;and in the siRICH1+TGF-β1 group,myocardial fibrosis marker genes,such as Col1 a1,Col3a1 and Acta2 were up-regulated at the expression level;phosphorylated SMAD2(p-SMAD2)and phosphorylated SMAD3(p-SMAD3)levels were down-regulated in the siRICH1 OE+TGF-β1 group.p-SMAD2 and P-SMAD3 levels were upregulated in the siRICH1+TGF-β1 group.Conclusion RICH1 inhibits TGF-β1-induced myo-cardial fibrosis;RICH1 inhibits TGF-β1-induced myo-cardial fibrosis by negatively regulating the SMAD2/3 signaling pathway.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Mitochondrial dynamics refer to two modes of move-ment:mitochondrial fission and mitochondrial fusion.Stimula-tion from internal and external sources promotes the occurrence of mitochondrial dynamic changes,supporting cellular functional changes to adapt to physiological and pathological changes.This article systematically reviews relevant literature,providing an o-verview of the dynamic changes in mitochondrial fission/fusion from both physiological and pathological perspectives.It summa-rizes the essence of these changes by highlighting functional al-terations,including ion homeostasis,redox balance,energy me-tabolism,and programmed death signaling,and reveals the un-derlying mechanisms of action.Additionally,by focusing on key cellular components in allergic diseases,it discusses the impact of functional alterations in mitochondrial dynamic division/fusion on allergic diseases.Progressively examining the concept,func-tional alterations,and impact on allergic diseases,this study es-tablishes a connection between mitochondrial fission/fusion dy-namics and key cellular components of allergic diseases.It con-structs a networked map that outlines how these dynamics modu-late the progression of allergic diseases through diverse cellular components,aiming to guide mechanistic studies and systematic treatments for these diseases.

Objective To analyze the serum metabolomic changes of preterm infants with bronchopulmonary dysplasia(BPD)at postmenstrual age(PMA)36 weeks,screen potential biomarkers and associated metabolic pathways,and assess their relationship with short-term respiratory outcomes.Methods A retrospective case-control study was conducted.Infants with gestational age 28-32 weeks admitted to the Children's Hospital Affiliated to Zhengzhou University from January to December 2024 were included.Twenty infants with BPD and 20 gestational age-,birth weight-,and sex-matched non-BPD preterm infants were included.Serum collected at PMA 36 weeks was subjected to untargeted metabolomics analysis,and associations with short-term respiratory outcomes were analyzed.Results Thirteen potential biomarkers distinguishing BPD were identified(area under the curve>0.75,P<0.05).Eight biomarkers—including terephthalic acid,phosphatidylinositol,fumarate,and lysophosphatidic acid—were significantly upregulated(FC≥1.5),while five biomarkers,such as 7α-hydroxy-3-oxo-4-cholestenoate ester and phosphatidylcholine,were significantly downregulated(FC≤1/1.5).Pathway analysis indicated five pathways associated with BPD,including glycerophospholipid metabolism and phenylalanine metabolism.Dysregulation of glycerophospholipid and bile acid metabolism may affect adverse short-term respiratory outcomes in infants with BPD.Conclusions The 13 significantly different metabolites may serve as biomarkers for the diagnosis of BPD.Glycerophospholipid metabolism is associated with the occurrence of BPD and with adverse short-term respiratory outcomes.

BACKGROUND:Previous studies have demonstrated that moxibustion can alleviate osteoarthritis-induced cartilage lesions and delay the progression of knee osteoarthritis. In a previous study conducted by our research group,it was found that regulating the circPan3/miR-667-5p/Ghrelin signaling pathway can enhance the level of autophagy in chondrocytes,thereby exerting a cartilage protective role in knee osteoarthritis. OBJECTIVE:To explore the effect of moxibustion on knee osteoarthritis cartilage in rats based on the circPan3/miR-667-5p/Ghrelin signaling pathway. METHODS:Sprague-Dawley rats were randomly divided into three groups (n=10 per group):sham operation,model,and moxibustion groups. A rat model of knee osteoarthritis was established in the latter two groups by anterior cruciate ligament transection and medial meniscus resection. Rats in the sham operation group underwent arthrotomy only. At 6 weeks after modeling,moxibustion intervention at Zusanli and Shenyu acupoints was applied in the moxibustion group,20 minutes daily for 4 weeks,while the other two groups did not receive any special treatment. After 4 weeks,histopathological staining was performed to observe the degree of synovial lesions and cartilage damage in the knee joint. Additionally,changes in the serum levels of inflammatory cytokines,interleukin-6 and tumor necrosis factor-α,were detected by enzyme-linked immunosorbent assay. Furthermore,chondrocytes isolated from the above three groups of rats were divided into three groups:a normal control group,a model group,and a moxibustion group. The expression levels of cartilage matrix anabolic molecules (type Ⅱ collagen and Sox9),matrix degradation molecules (matrix metalloproteinase 13 and ADAMTS5),autophagy markers (ATG5,Beclin-1,microtubule-associated protein 1 light chain 3),Ghrelin,CircPan3,and miR-667-5P were determined by western blot and qRT-PCR in each group. RESULTS AND CONCLUSION:After 4 weeks of treatment,the model group exhibited significant thickening of the synovium,infiltration of inflammatory cells,narrowing of the joint space,rough and uneven cartilage surfaces,thinning,reduction in the number of chondrocytes,a significant increase in synovitis and Osteoarthritis Research Society International scores,and a significant up-regulation of interleukin-6 and tumor necrosis factor-α levels (P<0.0001). In comparison,the sham operation group showed no significant changes. Compared with the model group,the moxibustion group exhibited a reduction in synovial thickening,a decrease in inflammatory cell infiltration,an increase in joint space,a reduction in cartilage roughness and loss of integrity,an increase in the number of chondrocytes,a reduction in synovitis and Osteoarthritis Research Society International scores,and a significant reduction in the levels of interleukin-6 and tumor necrosis factor-α (P<0.0001). The results of in vitro experiments demonstrated that the expression of matrix metalloproteinase 13,ADAMTS5,and miR-667-5P was elevated,while the expression of type Ⅱ collagen,Sox9,autophagy markers,Ghrelin,and Circpan3 was reduced in the model group compared with the normal control group (P<0.01). Moxibustion was found to reverse these changes in the moxibustion group compared with the model group (P<0.01). To conclude,moxibustion may enhance chondrocyte autophagy by modulating the circPan3/miR-667-5p/Ghrelin signaling pathway,which may inhibit knee osteoarthritis inflammation and cartilage destruction,exerting a protective effect on cartilage.

Mitochondrial dynamics refer to two modes of move-ment:mitochondrial fission and mitochondrial fusion.Stimula-tion from internal and external sources promotes the occurrence of mitochondrial dynamic changes,supporting cellular functional changes to adapt to physiological and pathological changes.This article systematically reviews relevant literature,providing an o-verview of the dynamic changes in mitochondrial fission/fusion from both physiological and pathological perspectives.It summa-rizes the essence of these changes by highlighting functional al-terations,including ion homeostasis,redox balance,energy me-tabolism,and programmed death signaling,and reveals the un-derlying mechanisms of action.Additionally,by focusing on key cellular components in allergic diseases,it discusses the impact of functional alterations in mitochondrial dynamic division/fusion on allergic diseases.Progressively examining the concept,func-tional alterations,and impact on allergic diseases,this study es-tablishes a connection between mitochondrial fission/fusion dy-namics and key cellular components of allergic diseases.It con-structs a networked map that outlines how these dynamics modu-late the progression of allergic diseases through diverse cellular components,aiming to guide mechanistic studies and systematic treatments for these diseases.

Meniere's disease represents an idiopathic inner ear disorder characterized by endolymphatic hy-drops.Currently,the research methods for identifying genes associated with this disease mainly involve first-genera-tion sequencing and second-generation sequencing.This article reviews research on the genetic study of Meniere's disease,mainly summarizing the candidate genes with repeated pedigree validation in familial Meniere's disease,as well as those frequently reported in sporadic Meniere's disease.

Objective To propose a dynamic early warning model based on machine learning methods and validate its predi-ctive efficacy so as to achieve precise assessment and early warning of mortality risk in patients with traumatic hypothermia.Methods Firstly,a total of 480 patients who met inclusion criteria were retrospectively selected from the eICU database and randomly divided into training and test sets at an 8∶2 ratio.Secondly,physiological parameters were extracted from these patients,and five machine learning algorithms including XGBoost,AdaBoost,LightGBM,logistic regression(LR)and random forest(RF)were employed respectively to develop dynamic mortality risk warning models for traumatic hypothermia patients,utilizing a 1-hour observation window.Thirdly,receiver operating characteristic curves(ROC)were plotted using the test set data and the effects of different warning windows on the model performance were analyzed by calculating the AUC.Finally,the interpretability of the models was analyzed using the SHapley Additive exPlanations(SHAP)algorithm to elucidate the contribution of each feature to predictive performance.Results The optimal warning window for the dynamic warning model constructed using the eICU database was 12 hours,and in case of 12-hour warning window the logistic regression model achieved the highest AUC of 0.935 and showed optimal predictive performance.The results of the interpretability analysis by the SHAP algorithm showed that body temperature was the feature that had the greatest impact on the model results,and its reduction was positively correlated with the increased risk of death.Conclusion The machine learning-based dynamic warning model for mortality risk in traumatic hypothermia patients enables real-time dynamic risk assessment,providing robust support for clinicians to identify the patient's condition changes at an early stage and references for the adjustment of clinical treatment programs.[Chinese Medical Equipment Journal,2025,46(3):9-14]

This study aims to explore the effects and mechanisms of 4'-O-methylbavachalcone(MeBavaC), an active compound from Psoraleae Fructus, in regulating white matter neuroinflammation to improve vascular cognitive impairment. Male Sprague-Dawley(SD) rats were randomly divided into four groups: sham group, model group, high-dose MeBavaC group(14 mg·kg~(-1)), and low-dose MeBavaC group(7 mg·kg~(-1)). The rat model of chronic cerebral hypoperfusion(CCH) was established using bilateral common carotid artery occlusion. The Morris water maze test was performed to evaluate the learning and memory abilities of the rats. Luxol fast blue staining, Nissl staining, immunofluorescence, immunohistochemistry, and transmission electron microscopy were utilized to observe the morphology and ultrastructure of the white matter myelin sheaths, axon integrity, the morphology and number of hippocampal neurons, and the loss and activation of glial cells in the white matter. Transcriptome analysis was performed to explore the potential mechanisms of white matter injury induced by CCH. Western blot and quantitative real-time polymerase chain reaction(qRT-PCR) assays were conducted to measure the expression levels of NOD-like receptor protein 3(NLRP3), absent in melanoma 2(AIM2), gasdermin D(GSDMD), cysteinyl aspartate-specific proteinase-1(caspase-1), interleukin-18(IL-18), interleukin-1β(IL-1β), erythropoietin(EPO), nuclear factor erythroid 2-related factor 2(Nrf2), and heme oxygenase-1(HO-1) in the white matter of rats. The results showed that compared with the model group, MeBavaC significantly improved the learning and memory abilities of rats with CCH, improved the damage of white matter myelin sheath, maintained axonal integrity, reduced the loss of hippocampal neurons and oligodendrocytes in the white matter, inhibited the activation of microglia and the proliferation of astrocytes in the white matter, and suppressed the NLRP3/AIM2/caspase-1/GSDMD pathway. The expression levels of inflammatory cytokines IL-1β and IL-18 were significantly reduced, while EPO expression and the expression of Nrf2/HO-1 antioxidant pathway were notably elevated. In conclusion, MeBavaC can alleviate cognitive impairment in rats with CCH and suppress neuroinflammation in cerebral white matter. The mechanism of action may involve activation of EPO activity, promotion of endogenous antioxidant pathways, and inhibition of neuroinflammation in the white matter. This study suggests that MeBavaC exhibits antioxidant and anti-neuroinflammatory effects, showing potential application in improving cognitive dysfunction.
Animals ; Male ; Rats, Sprague-Dawley ; NF-E2-Related Factor 2/immunology* ; Rats ; Chalcones/administration & dosage* ; Cognitive Dysfunction/metabolism* ; Signal Transduction/drug effects* ; Neuroinflammatory Diseases/drug therapy* ; Heme Oxygenase-1/metabolism* ; Humans ; Heme Oxygenase (Decyclizing)/genetics*

This study investigated the therapeutic effects of Yiguanjian on dry eye in rats and its mechanisms involving the T helper cell 17(Th17)/regulatory T cell(Treg) balance. The rat model of dry eye was established by administrating 0.2% benzalkonium chloride solution in eye drops. After successful modeling, the rats were treated with Yiguanjian for 4 consecutive weeks. The Schirmer test was carried out to assess the lacrimal gland function, corneal fluorescence staining to detect corneal injury, hematoxylin-eosin staining to observe corneal histopathology, enzyme-linked immunosorbent assay to measure serum levels of interleukin(IL)-6, IL-8, IL-17A, IL-21, and tumor necrosis factor-α(TNF-α), RT-qPCR to analyze mRNA levels of retinoic acid receptor-related orphan receptor gamma t(RORγt) and forkhead box protein p3(Foxp3) in the corneal tissue, immunofluorescence double staining to evaluate RORγt and Foxp3 expression in the lacrimal gland tissue, and Western blot to quantify the protein levels of signal transducer and activator of transcription 3(STAT3), phosphorylated STAT3(p-STAT3), Janus kinase 2(Jak2), phosphorylated Jak2(p-Jak2), RORγt, and Foxp3 in the corneal tissue. The results demonstrated that Yiguanjian increased tear secretion(P<0.01), alleviated corneal damage and pathological changes, and lowered the serum levels of IL-6, IL-8, IL-17A, IL-21, and TNF-α(P<0.05) in model rats. Additionally, Yiguanjian decreased the ratio of RORγt to Foxp3 in the corneal and lacrimal gland tissue(P<0.01), downregulated the protein levels of STAT3, Jak2, and RORγt(P<0.05), upregulated the protein level of Foxp3(P<0.05), and inhibited phosphorylation of STAT3 and Jak2(P<0.01). These findings indicate that Yiguanjian ameliorates ocular surface dysfunction in dry eye rats by restoring Th17/Treg balance in the corneal and lacrimal gland tissue and suppressing systemic inflammatory cytokine release, thus mitigating ocular surface inflammation.
Animals ; Rats ; T-Lymphocytes, Regulatory/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Th17 Cells/immunology* ; Male ; Rats, Sprague-Dawley ; Dry Eye Syndromes/genetics* ; Nuclear Receptor Subfamily 1, Group F, Member 3/immunology* ; Lacrimal Apparatus/immunology* ; Humans ; STAT3 Transcription Factor/immunology*